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1. Real-world multidisciplinary outcomes of onasemnogene abeparvovec monotherapy in patients with spinal muscular atrophy type 1: experience of the French cohort in the first three years of treatment

Author: Isabelle Desguerre, Rémi Barrois, Frédérique Audic, Christine Barnerias, Brigitte Chabrol, Jean Baptiste Davion, Julien Durigneux, Caroline Espil-Taris, Marta Gomez-Garcia de la Banda, Marine Guichard, Arnaud Isapof, Marie Christine Nougues, Vincent Laugel, Laure Le Goff, Sandra Mercier, Anne Pervillé, Christian Richelme, Marie Thibaud, Catherine Sarret, Cyril Schweitzer, Hervé Testard, Valérie Trommsdorff, Catherine Vanhulle, Ulrike Walther-Louvier, Cécilia Altuzarra, Mondher Chouchane, Juliette Ropars, Susana Quijano-Roy, and Claude Cances
Subjects: Spinal muscular atrophy, Gene transfer therapy, Real-world outcome, Medicine
Abstract: Abstract Background Spinal muscular atrophy type 1 (SMA1) is the most severe and early form of SMA, a genetic disease with motor neuron degeneration. Onasemnogene abeparvovec gene transfer therapy (GT) has changed the natural history of SMA1, but real-world data are scarce. Methods A French national expert committee identified 95 newly diagnosed treatment-naive SMA1 patients between June 2019 and June 2022. We prospectively report on children treated with GT as the first and only therapy who had more than one-year of follow-up. Results Forty-six SMA1 patients received GT. Twelve patients received other treatments. Patients with respiratory insufficiency were oriented toward palliative care after discussion with families. Twenty-nine of the treated patients with more than 12 months of follow-up were included in the follow-up analysis. Among them, 17 had 24 months of follow-up. The mean age at treatment was 7.5 (2.1–12.5) months. Twenty-two patients had two SMN2 copies, and seven had three copies. One infant died in the month following GT due to severe thrombotic microangiopathy, and another died due to respiratory distress. Among the 17 patients with 24 months of follow-up, 90% required spinal bracing (15/17), three patients required nocturnal noninvasive ventilation, and two needed gastrostomy. Concerning motor milestones at the 24-month follow-up, all patients held their head, 15/17 sat for 30 s unassisted, and 12/17 stood with aid. Motor scores (CHOPINTEND and HINE-2) and thoracic circumference significantly improved in all patients. Conclusions Our study shows favorable motor outcomes and preserved respiratory and feeding functions in treatment-naive SMA1 infants treated by GT as the first and only therapy before respiratory and bulbar dysfunctions occurred. Nevertheless, almost all patients developed spinal deformities.
Published: 2024
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2. New mutation in the β1 propeller domain of LRP4 responsible for congenital myasthenic syndrome associated with Cenani–Lenz syndrome

Author: Marion Masingue, Olivia Cattaneo, Nicolas Wolff, Céline Buon, Damien Sternberg, Morgane Euchparmakian, Myriam Boex, Anthony Behin, Kamel Mamchaouhi, Thierry Maisonobe, Marie-Christine Nougues, Arnaud Isapof, Bertrand Fontaine, Julien Messéant, Bruno Eymard, Laure Strochlic, and Stéphanie Bauché
Subjects: Medicine, Science
Abstract: Abstract Congenital myasthenic syndromes (CMS) are a clinically and genetically heterogeneous group of rare diseases due to mutations in neuromuscular junction (NMJ) protein-coding genes. Until now, many mutations encoding postsynaptic proteins as Agrin, MuSK and LRP4 have been identified as responsible for increasingly complex CMS phenotypes. The majority of mutations identified in LRP4 gene causes bone diseases including CLS and sclerosteosis-2 and rare cases of CMS with mutations in LRP4 gene has been described so far. In the French cohort of CMS patients, we identified a novel LRP4 homozygous missense mutation (c.1820A > G; p.Thy607Cys) within the β1 propeller domain in a patient presenting CMS symptoms, including muscle weakness, fluctuating fatigability and a decrement in compound muscle action potential in spinal accessory nerves, associated with congenital agenesis of the hands and feet and renal malformation. Mechanistic expression studies show a significant decrease of AChR aggregation in cultured patient myotubes, as well as altered in vitro binding of agrin and Wnt11 ligands to the mutated β1 propeller domain of LRP4 explaining the dual phenotype characterized clinically and electoneuromyographically in the patient. These results expand the LRP4 mutations spectrum associated with a previously undescribed clinical association involving impaired neuromuscular transmission and limb deformities and highlighting the critical role of a yet poorly described domain of LRP4 at the NMJ. This study raises the question of the frequency of this rare neuromuscular form and the future diagnosis and management of these cases.
Published: 2023
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3. GGPS1‐associated muscular dystrophy with and without hearing loss

Author: Rauan Kaiyrzhanov, Luke Perry, Clarissa Rocca, Maha S. Zaki, Heba Hosny, Cristiane Araujo Martins Moreno, Rahul Phadke, Irina Zaharieva, Clara Camelo Gontijo, Christian Beetz, Veronica Pini, Mojtaba Movahedinia, Edmar Zanoteli, Stephanie DiTroia, Sandrine Vuillaumier‐Barrot, Arnaud Isapof, Mohammad Yahya Vahidi Mehrjardi, Nasrin Ghasemi, Anna Sarkozy, Francesco Muntoni, Sandra Whalen, Barbara Vona, Henry Houlden, and Reza Maroofian
Subjects: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract: Abstract Ultra‐rare biallelic pathogenic variants in geranylgeranyl diphosphate synthase 1 (GGPS1) have recently been associated with muscular dystrophy/hearing loss/ovarian insufficiency syndrome. Here, we describe 11 affected individuals from four unpublished families with ultra‐rare missense variants in GGPS1 and provide follow‐up details from a previously reported family. Our cohort replicated most of the previously described clinical features of GGPS1 deficiency; however, hearing loss was present in only 46% of the individuals. This report consolidates the disease‐causing role of biallelic variants in GGPS1 and demonstrates that hearing loss and ovarian insufficiency might be a variable feature of the GGPS1‐associated muscular dystrophy.
Published: 2022
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4. Parents' dilemma: A therapeutic decision for children with spinal muscular atrophy (SMA) type 1

Author: Sophie Boursange, Marco Araneda, Caroline Stalens, Isabelle Desguerre, Christine Barnerias, Marie-Christine Nougues, Arnaud Isapof, Susana Quijano-Roy, Nadia Blu Genestine, Laetitia Ouillade, Maripaz Martinez Jalilie, Claudia Castiglioni, Odile Boespflug-Tanguy, Marcela Gargiulo, and The SMAPAR Study Group
Subjects: dilemmatic decisions, palliative care, parents, caregivers, spinal amyotrophy type 1, SMAPAR Study, Pediatrics, RJ1-570
Abstract: BackgroundSMA type 1 is a severe neurodegenerative disorder that, in the absence of curative treatment, leads to death before 1 year of age without ventilatory support. Three innovative therapies are available to increase life expectancy.Purpose(i) To increase knowledge about parents' experiences with their decision to have opted for an innovative therapy; (ii) to assess the middle-term psychological consequences in the parents' lives.MethodsWe used an in-depth interview; a self-administrated questionnaire and self-report scales (BDI-II, STAI-Y, PSI-SF, SOC-13, PBA, DAS 16 and FICD). We compared parents hesitant before the decision to parents who were not-hesitant and the group of parents whose child was treated with gene therapy (GT) to parents whose child received another innovative therapy.Main resultsWe included n = 18 parents of 13 children. Parent's mean age was 34.7 (±5.2), child's average age was 44.3 months (±38.0). Retrospectively, most parents felt involved by doctors in decision-making on treatment, they felt their point of view was considered and were satisfied with the effects of the treatment. The group of parents “non-hesitant” was more depressed (p
Published: 2022
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5. Effects of nusinersen after one year of treatment in 123 children with SMA type 1 or 2: a French real-life observational study

Author: Frédérique Audic, Marta Gomez Garcia de la Banda, Delphine Bernoux, Paola Ramirez-Garcia, Julien Durigneux, Christine Barnerias, Arnaud Isapof, Jean-Marie Cuisset, Claude Cances, Christian Richelme, Carole Vuillerot, Vincent Laugel, Juliette Ropars, Cécilia Altuzarra, Caroline Espil-Taris, Ulrike Walther-Louvier, Pascal Sabouraud, Mondher Chouchane, Catherine Vanhulle, Valérie Trommsdorff, Anne Pervillé, Hervé Testard, Emmanuelle Lagrue, Catherine Sarret, Anne-Laude Avice, Pierre Beze-Beyrie, Vanessa Pauly, Susana Quijano-Roy, Brigitte Chabrol, and Isabelle Desguerre
Subjects: Spinal muscular atrophy type I, Spinal muscular atrophy type II, Nusinersen, Motor function measure, MFM, Medicine
Abstract: Abstract Background Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord. Nusinersen has been covered by public healthcare in France since May 2017. The aim of this article is to report results after 1 year of treatment with intrathecal nusinersen in children with SMA types 1 and 2 in France. Comparisons between treatment onset (T0) and after 1 year of treatment (Y1) were made in terms of motor function and need for nutritional and ventilatory support. Motor development milestone achievements were evaluated using the modified Hammersmith Infant Neurologic Examination–Part 2 (HINE-2) for patients under 2 years of age and Motor Function Measure (MFM) scores for patients over 2 years of age. Results Data on 204 SMA patients (type 1 or 2) were retrospectively collected from the 23 French centers for neuromuscular diseases. One hundred and twenty three patients had been treated for at least 1 year and were included, 34 of whom were classified as type 1 (10 as type 1a/b and 24 as type 1c) and 89 as type 2. Survival motor Neuron 2 (SMN2) copy numbers were available for all but 6 patients. Patients under 2 years of age (n = 30), had significantly higher HINE-2 scores at year 1 than at treatment onset but used more nutritional and ventilatory support. The 68 patients over 2 years of age evaluated with the Motor Function Measure test had significantly higher overall scores after 1 year, indicating that their motor function had improved. The scores were higher in the axial and proximal motor function (D2) and distal motor function (D3) parts of the MFM scale, but there was no significant difference for standing and transfer scores (D1). No child in either of the two groups achieved walking. Conclusion Nusinersen offers life-changing benefits for children with SMA, particularly those with more severe forms of the disorder. Caregiver assessments are positive. Nevertheless, patients remain severely disabled and still require intensive support care. This new treatment raises new ethical challenges.
Published: 2020
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6. Author Correction: CHD3 helicase domain mutations cause a neurodevelopmental syndrome with macrocephaly and impaired speech and language

Author: Lot Snijders Blok, Justine Rousseau, Joanna Twist, Sophie Ehresmann, Motoki Takaku, Hanka Venselaar, Lance H. Rodan, Catherine B. Nowak, Jessica Douglas, Kathryn J. Swoboda, Marcie A. Steeves, Inderneel Sahai, Connie T. R. M. Stumpel, Alexander P. A. Stegmann, Patricia Wheeler, Marcia Willing, Elise Fiala, Aaina Kochhar, William T. Gibson, Ana S. A. Cohen, Ruky Agbahovbe, A. Micheil Innes, P. Y. Billie Au, Julia Rankin, Ilse J. Anderson, Steven A. Skinner, Raymond J. Louie, Hannah E. Warren, Alexandra Afenjar, Boris Keren, Caroline Nava, Julien Buratti, Arnaud Isapof, Diana Rodriguez, Raymond Lewandowski, Jennifer Propst, Ton van Essen, Murim Choi, Sangmoon Lee, Jong H. Chae, Susan Price, Rhonda E. Schnur, Ganka Douglas, Ingrid M. Wentzensen, Christiane Zweier, André Reis, Martin G. Bialer, Christine Moore, Marije Koopmans, Eva H. Brilstra, Glen R. Monroe, Koen L. I. van Gassen, Ellen van Binsbergen, Ruth Newbury-Ecob, Lucy Bownass, Ingrid Bader, Johannes A. Mayr, Saskia B. Wortmann, Kathy J. Jakielski, Edythe A. Strand, Katja Kloth, Tatjana Bierhals, The DDD study, John D. Roberts, Robert M. Petrovich, Shinichi Machida, Hitoshi Kurumizaka, Stefan Lelieveld, Rolph Pfundt, Sandra Jansen, Pelagia Deriziotis, Laurence Faivre, Julien Thevenon, Mirna Assoum, Lawrence Shriberg, Tjitske Kleefstra, Han G. Brunner, Paul A. Wade, Simon E. Fisher, and Philippe M. Campeau
Subjects: Science
Abstract: The HTML and PDF versions of this Article were updated after publication to remove images of one individual from Figure 1.
Published: 2019
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7. CHD3 helicase domain mutations cause a neurodevelopmental syndrome with macrocephaly and impaired speech and language

Author: Lot Snijders Blok, Justine Rousseau, Joanna Twist, Sophie Ehresmann, Motoki Takaku, Hanka Venselaar, Lance H. Rodan, Catherine B. Nowak, Jessica Douglas, Kathryn J. Swoboda, Marcie A. Steeves, Inderneel Sahai, Connie T. R. M. Stumpel, Alexander P. A. Stegmann, Patricia Wheeler, Marcia Willing, Elise Fiala, Aaina Kochhar, William T. Gibson, Ana S. A. Cohen, Ruky Agbahovbe, A. Micheil Innes, P. Y. Billie Au, Julia Rankin, Ilse J. Anderson, Steven A. Skinner, Raymond J. Louie, Hannah E. Warren, Alexandra Afenjar, Boris Keren, Caroline Nava, Julien Buratti, Arnaud Isapof, Diana Rodriguez, Raymond Lewandowski, Jennifer Propst, Ton van Essen, Murim Choi, Sangmoon Lee, Jong H. Chae, Susan Price, Rhonda E. Schnur, Ganka Douglas, Ingrid M. Wentzensen, Christiane Zweier, André Reis, Martin G. Bialer, Christine Moore, Marije Koopmans, Eva H. Brilstra, Glen R. Monroe, Koen L. I. van Gassen, Ellen van Binsbergen, Ruth Newbury-Ecob, Lucy Bownass, Ingrid Bader, Johannes A. Mayr, Saskia B. Wortmann, Kathy J. Jakielski, Edythe A. Strand, Katja Kloth, Tatjana Bierhals, The DDD study, John D. Roberts, Robert M. Petrovich, Shinichi Machida, Hitoshi Kurumizaka, Stefan Lelieveld, Rolph Pfundt, Sandra Jansen, Pelagia Deriziotis, Laurence Faivre, Julien Thevenon, Mirna Assoum, Lawrence Shriberg, Tjitske Kleefstra, Han G. Brunner, Paul A. Wade, Simon E. Fisher, and Philippe M. Campeau
Subjects: Science
Abstract: Chromodomain Helicase DNA-binding (CHD) proteins have been implicated in neurodevelopmental processes. Here, the authors identify missense variants in CHD3 that disturb its chromatin remodeling activities and cause a neurodevelopmental disorder with macrocephaly and speech and language impairment.
Published: 2018
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8. Respiratory function and sleep in children with myotonic dystrophy type 1

Author: Marie Cheminelle, Marie-Christine Nougues, Arnaud Isapof, Guillaume Aubertin, Harriet Corvol, Nicole Beydon, and Jessica Taytard
Subjects: Neurology, Pediatrics, Perinatology and Child Health, Neurology (clinical), Genetics (clinical)
Published: 2023

9. <scp> GGPS1 </scp> ‐associated muscular dystrophy with and without hearing loss

Author: Rauan Kaiyrzhanov, Luke Perry, Clarissa Rocca, Maha S. Zaki, Heba Hosny, Cristiane Araujo Martins Moreno, Rahul Phadke, Irina Zaharieva, Clara Camelo Gontijo, Christian Beetz, Veronica Pini, Mojtaba Movahedinia, Edmar Zanoteli, Stephanie DiTroia, Sandrine Vuillaumier‐Barrot, Arnaud Isapof, Mohammad Yahya Vahidi Mehrjardi, Nasrin Ghasemi, Anna Sarkozy, Francesco Muntoni, Sandra Whalen, Barbara Vona, Henry Houlden, and Reza Maroofian
Subjects: General Neuroscience, Mutation, Missense, Farnesyltranstransferase, Humans, Female, Geranyltranstransferase, Neurology (clinical), Deafness, Primary Ovarian Insufficiency, Dimethylallyltranstransferase, Hearing Loss, Muscular Dystrophies
Abstract: Ultra-rare biallelic pathogenic variants in geranylgeranyl diphosphate synthase 1 (GGPS1) have recently been associated with muscular dystrophy/hearing loss/ovarian insufficiency syndrome. Here, we describe 11 affected individuals from four unpublished families with ultra-rare missense variants in GGPS1 and provide follow-up details from a previously reported family. Our cohort replicated most of the previously described clinical features of GGPS1 deficiency; however, hearing loss was present in only 46% of the individuals. This report consolidates the disease-causing role of biallelic variants in GGPS1 and demonstrates that hearing loss and ovarian insufficiency might be a variable feature of the GGPS1-associated muscular dystrophy.
Published: 2022

10. Rituximab Therapy in the Treatment of Juvenile Myasthenia Gravis

Author: Agathe Molimard, Cyril Gitiaux, Christine Barnerias, Frédérique Audic, Arnaud Isapof, Ulrike Walther-Louvier, Claude Cances, Caroline Espil-Taris, Jean-Baptiste Davion, Susana Quijano-Roy, Coraline Grisel, Brigitte Chabrol, and Isabelle Desguerre
Subjects: Cortisone, Myasthenia Gravis, Humans, Immunologic Factors, Neurology (clinical), Child, Rituximab, Immunosuppressive Agents
Abstract: Background and ObjectivesCorticosteroids are the first-line immunosuppressants in the management of juvenile myasthenia gravis despite their adverse effects. The place of new immunosuppressive therapies is not clearly defined by the last international consensus held in March 2019 due to the lack of clinical trials. The aim of this study is to describe the use of rituximab and its efficacy and safety in 8 main pediatric centers of the French neuromuscular reference network to propose a new place in the therapeutic strategy of juvenile myasthenia gravis.MethodsWe conducted a retrospective multicenter study from January 1, 2009, to April 30, 2020, including a large cohort of children with myasthenia gravis in 8 main French pediatric reference centers of the FILNEMUS network. The type of myasthenia, different lines of immunosuppressive treatment, and clinical course of the patients were collected. To evaluate the efficacy of rituximab, we studied the clinical course of patients on immunosuppressive therapy. Outcome was defined as the clinical and therapeutic status of patients at the last visit: stable without immunosuppressants, stable with immunosuppressants, or unstable.ResultsWe included 74 patients: 18 children with ocular form and 56 children with generalized form. Of the 37 patients who required immunosuppressive therapy, 27 were treated with rituximab. Patients treated with rituximab had a better outcome than patients treated with conventional immunosuppressants (p= 0.006). The use of rituximab as a first-line immunosuppressant showed a better efficacy with a discontinuation of immunosuppressants in 75% of patients (vs 25%,p= 0.04) and results in cortisone sparing (42% vs 92%,p= 0.03) compared with rituximab treatment as a second- or third-line immunosuppression. Rituximab was well tolerated; no adverse effect was observed.DiscussionThe use of rituximab has increased in France over the last 10 years as a first-line immunosuppressant. This study suggests good tolerability and efficacy of rituximab in juvenile myasthenia gravis. Early use appears to improve outcomes and facilitate cortisone sparing in antibody-positive generalized juvenile myasthenia.Classification of EvidenceThis study provides Class III evidence that for children with MG, rituximab is effective and well tolerated.
Published: 2022

11. Effect of nusinersen after three years of treatment in 61 young children with SMA type 1 or 2: a French real-life observational study

Author: frédérique AUDIC, Sonia M Dubois, Julien Durigneux, Christine Barnerias, Arnaud Isapof, Marie-Christine Nougues, Jean-Baptiste Davion, Christian Richelme, Carole Vuillerot, Laure Legoff, Pascal Sabouraud, Claude Cances, Vincent Laugel, Juliette Ropars, Caroline Espil-Taris, Valérie Trommsdorff, Anne Pervillé, Marta Gomez Garcia de la Banda, Hervé Testard, Mondher Chouchane, Ulrike Walther-Louvier, Cyril Schweizer, Cécile Halbert, Myriam Badri, Vanessa Pauly, Susana Quijano-Roy, Brigitte Chabrol, and Isabelle Desguerre
Abstract: Background Spinal muscular atrophy (SMA) is a rare genetic neuromuscular disorder due to an autosomal recessive mutation in the survival motor neuron 1 gene (SMN1) causing degeneration of the anterior horn cells of the spinal cord and resulting in muscle atrophy. The aim of this paper is to report a 36-month follow-up of children with SMA treated with nusinersen before the age of 3 years. Change in motor function, nutritional and ventilatory support and orthopedics outcomes were evaluated at baseline and 36 months after intrathecal nusinersen and correlated with SMA type and SMN2 copy number. Results We report 88% of the patients who have gained new motor skills during the 3-years period, reaching standing without help and walking with help for 12/37 and 10/37 patients harboring 3 SMN2 copies respectively. No patients with 2 copies SMN2 can stand alone or walk. Patients bearing 3 copies of SMN2 are also more likely to be preserved from respiratory, nutritional and orthopedic complications than patients with 2 SMN2 copies. Conclusion Eventhough SMA patients improve with nusinersen, a lower number of SMN2 gene copies remains a predictor a of poorer evolution under treatment.
Published: 2022

12. Association between prophylactic angiotensin-converting enzyme inhibitors and overall survival in Duchenne muscular dystrophy—analysis of registry data

Author: Caroline Ovaert, Sylvie Tuffery-Giraud, Sarah Leonard-Louis, Anthony Béhin, Sophie Guillaumont, Maximilien Sochala, Emmanuelle Campana-Salort, Frédérique Audic, Michèle Mayer, Damien Bonnet, Raul Juntas Morales, Mireille Cossée, Isabelle Desguerre, Christophe Meune, Pascal Laforêt, Rabah Ben Yaou, Brigitte Chabrol, Djillali Annane, David Orlikowski, François Godart, Malika Saadi, Helge Amthor, Tanya Stojkovic, Ulrike Walther-Louvier, Frédéric Lofaso, Pascal Amedro, Raphaël Porcher, Céline Tard, Claire Delcourte, Vincent Tiffreau, Karim Wahbi, Christine Barnerias, Guillaume Bassez, Bertrand Fontaine, Arnaud Isapof, Gregoire De La Villeon, Guy Vaksmann, François Rivier, Denis Duboc, Henri Marc Bécane, Philippe Ravaud, Hélène Prigent, Emmanuelle Jaillette, Abdallah Fayssoil, Bruno Eymard, Université de Lille, Univ. Artois, Univ. Littoral Côte d’Opale, Unité de Recherche Pluridisciplinaire Sport, Santé, Société (URePSSS) - ULR 7369 - ULR 4488 [URePSSS], Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Handicap neuromusculaire : Physiopathologie, Biothérapie et Pharmacologies appliquées (END-ICAP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Clinique de pneumologie [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche Pluridisciplinaire Sport, Santé, Société (URePSSS) - ULR 7369 - ULR 4488 (URePSSS), Université d'Artois (UA)-Université du Littoral Côte d'Opale (ULCO)-Université de Lille, Neurologie, maladies neuro-musculaires [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Pitié-Salpêtrière [AP-HP], Hôpital Cochin [AP-HP], Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Filière Neuromusculaire (FILNEMUS), Infection et inflammation (2I), Université de Montpellier (UM), Centre Hospitalier de Versailles André Mignot (CHV), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Centre d’Investigation Clinique 1429 [Garches] (CIC 1429), Hôpital Raymond Poincaré [AP-HP]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de cardiologie Pédiatrique [Marseille], Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital Raymond Poincaré [AP-HP], Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)
Subjects: Duchenne muscular dystrophy, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Cardiomyopathy, Angiotensin-Converting Enzyme Inhibitors, Heart failure, Angiotensin-converting enzyme inhibitors, 030204 cardiovascular system & hematology, Lower risk, Ventricular Function, Left, Angiotensin Receptor Antagonists, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, medicine, Humans, Registries, cardiovascular diseases, 030212 general & internal medicine, Medical prescription, Child, ComputingMilieux_MISCELLANEOUS, Heart Failure, biology, business.industry, Proportional hazards model, Hazard ratio, Angiotensin-converting enzyme, medicine.disease, Confidence interval, 3. Good health, Muscular Dystrophy, Duchenne, Treatment Outcome, Child, Preschool, biology.protein, Cardiology and Cardiovascular Medicine, business, cardiomyopathy
Abstract: Aims To estimate the effect of prophylactic angiotensin-converting enzyme inhibitors (ACEi) on survival in Duchenne muscular dystrophy (DMD). Methods and results We analysed the data from the French multicentre DMD Heart Registry (ClinicalTrials.gov: NCT03443115). We estimated the association between the prophylactic prescription of ACEi and event-free survival in 668 patients aged 8 to 13 years, with normal left ventricular function, using (i) a Cox model with intervention as a time-dependent covariate, (ii) a propensity-based analysis comparing ACEi treatment vs. no treatment, and (iii) a set of sensitivity analyses. The study outcomes were overall survival and hospitalizations for heart failure (HF) or acute respiratory failure. Among the 668 patients included in the DMD Heart Registry, 576 (mean age 6.1 ± 2.8 years) were eligible for this study, of whom 390 were treated with ACEi prophylactically. Death occurred in 53 patients (13.5%) who were and 60 patients (32.3%) who were not treated prophylactically with ACEi, respectively. In a Cox model with intervention as a time-dependent variable, the hazard ratio (HR) associated with ACEi treatment was 0.49 [95% confidence interval (CI) 0.34–0.72] and 0.47 (95% CI 0.31–0.17) for overall mortality after adjustment for baseline variables. In the propensity-based analysis, 278 patients were included in the treatment group and 834 in the control group, with 18.5% and 30.4% 12-year estimated probability of death, respectively. ACEi were associated with a lower risk of death (HR 0.39; 95% CI 0.17–0.92) and hospitalization for HF (HR 0.16; 95% CI 0.04–0.62). All other sensitivity analyses yielded similar results. Conclusion Prophylactic ACEi treatment in DMD was associated with a significantly higher overall survival and lower rates of hospitalization for HF.
Published: 2021

13. Long-Reads Sequencing Strategy to Localize Variants in TTN Repeated Domains

Author: Aurélien Perrin, Charles Van Goethem, Corinne Thèze, Jacques Puechberty, Thomas Guignard, Bérénice Lecardonnel, Delphine Lacourt, Corinne Métay, Arnaud Isapof, Sandra Whalen, Ana Ferreiro, Marie-Christine Arne-Bes, Susana Quijano-Roy, Juliette Nectoux, France Leturcq, Pascale Richard, Marion Larrieux, Anne Bergougnoux, Franck Pellestor, Michel Koenig, Mireille Cossée, MORNET, Dominique, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Arnaud de Villeneuve [CHRU Montpellier], Unité de Génétique Chromosomique [Montpellier], Département de Génétique Médicale, Maladies Rares et Médecine Personnalisée [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Trousseau [APHP], Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre Hospitalier Universitaire de Purpan (CHU Purpan), Handicap neuromusculaire : Physiopathologie, Biothérapie et Pharmacologies appliquées (END-ICAP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Raymond Poincaré [AP-HP], Université Paris-Saclay, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Supported by AFM 21384 grant [The French Muscular Dystrophy Association (AFM-Téléthon)] (A.P.), the Délégation à la Recherche Clinique et à l’Innovation du Groupement de Coopération Sanitaire de la Mission d’Enseignement, de Recherche, de Référence et d’Innovation de Montpellier-Nîmes (A.P.), and the research platform Chromostem., and C.T. and J.P. contributed equally to this work. F.P. and M.K. contributed equally to this work.
Subjects: MESH: Alternative Splicing, MESH: genetics Connectin, Exons, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, MESH: genetics, Pathology and Forensic Medicine, MESH: genetics Exons, MESH: genetics Humans Muscular Diseases, Alternative Splicing, MESH: genetics Protein Isoforms, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Muscular Diseases, Molecular Medicine, Humans, Protein Isoforms, Connectin
Abstract: International audience; Titin protein is responsible for muscle elasticity. The TTN gene, composed of 364 exons, is subjected to extensive alternative splicing and leads to different isoforms expressed in skeletal and cardiac muscle. Variants in TTN are responsible for myopathies with a wide phenotypic spectrum and autosomal dominant or recessive transmission. The I-band coding domain, highly subject to alternative splicing, contains a three-zone block of repeated sequences with 99% homology. Sequencing and localization of variants in these areas are complex when using short-reads sequencing, a second-generation sequencing technique. We have implemented a protocol based on the third-generation sequencing technology (long-reads sequencing). This new method allows us to localize variants in these repeated areas to improve the diagnosis of TTN-related myopathies and offer the analysis of relatives in postnatal or in prenatal screening.
Published: 2022

14. Evidence-Based, Implementable Motor Rehabilitation Guidelines for Individuals With Cerebral Palsy

Author: Anthony Demont, Michel Gedda, Céline Lager, Capucine de Lattre, Yann Gary, Elisabeth Keroulle, Brigitte Feuillerat, Hervé Caudan, Zoé Sancelme, Arnaud Isapof, Elke Viehweger, Matthieu Chatelin, Marianne Hochard, Julia Boivin, Pascale Vurpillat, Nathalie Genès, Xavier de Boissezon, Audrey Fontaine, and Sylvain Brochard
Subjects: Adolescent, Cerebral Palsy, Muscles, Humans, Neurology (clinical), Child, Gait Disorders, Neurologic, Physical Therapy Modalities, Exercise Therapy
Abstract: BackgroundCerebral palsy is a life-long condition that causes heterogeneous motor disorders. Motor rehabilitation interventions must be adapted to the topography of the symptoms, ambulatory capacity, and age of the individual. Current guidelines do not differentiate between the different profiles of individuals with cerebral palsy, which limits their implementation.ObjectivesTo develop evidence-based, implementable guidelines for motor rehabilitation interventions for individuals with cerebral palsy according to the age, topography of the cerebral palsy, and ambulatory capacity of the individual and to determine a level of priority for each intervention.MethodsWe used a mixed methods design that combined a systematic review of the literature on available motor rehabilitation interventions with expert opinions. Based on the French National Authority for Health methodology, recommendations were graded as strong, conditional, or weak. Interventions were then prioritized by the experts according to both the evidence and their own opinions on relevance and implementability to provide a guide for clinicians. All recommendations were approved by experts who were independent from the working group.ResultsStrong recommendations as first-line treatments were made for gait training, physical activities, and hand-arm bimanual intensive therapy for all children and adolescents with cerebral palsy. Moderate recommendations were made against passive joint mobilizations, muscle stretching, prolonged stretching with the limb fixed, and neurodevelopmental therapies for all children and adolescents with cerebral palsy. Strong recommendations as first-line treatments were made for gait training for all adults with cerebral palsy and moderate recommendations as moderate importance interventions for strengthening exercises and ankle-foot orthoses for motor impairment of the feet and the ankles.DiscussionThese guidelines, which combine research evidence and expert opinions, could help individuals with cerebral palsy and their families to codetermine rehabilitation goals with health professionals, according to their preferences.
Published: 2022

15. La confidentialité dans les équipes

Author: Arnaud Isapof
Subjects: General Earth and Planetary Sciences, General Environmental Science
Abstract: Les exigences de technicite dans le domaine medical et l’accroissement des connaissances de la sante permettant d’offrir des diagnostics toujours plus precis, des pronostics plus probables, des soins et des traitements toujours plus specifiques aboutissent a une hyperspecialisation necessaire des competences medicales, paramedicales (infirmiere, kinesitherapeute, orthophoniste, ergotherapeute…) et psychologiques. Cette fragmentation et cette hyperspecialisation des connaissances de la sante touchant a la fois le diagnostic et le soin, particulierement, rendent necessaire la segmentation des tâches et son corollaire le travail en equipe et en reseau. L’une des caracteristiques du travail en equipe est le partage des informations necessaires a la prise en charge du patient. Ces interactions impliquant les membres de l’equipe de soins s’effectuent principalement de maniere verbale, mais egalement par le biais de la communication d’informations issues du dossier medical et par voie informatique. Il est alors necessaire de s’interroger sur la notion d’equipe de soins : quels sont les professionnels impliques dans le soin d’un patient ? Quelles sont les informations a transmettre a chacun ? N’y a-t-il pas incompatibilite entre la notion de secret medical et la necessaire communication dans les equipes ? Enfin quelle place pour les outils numeriques a disposition facilitant ces echanges ?
Published: 2019

16. Development and Validation of a New Risk Prediction Score for Life-Threatening Ventricular Tachyarrhythmias in Laminopathies

Author: Mélanie Fradin, Nicolas Sadoul, Xavier Waintraub, Didier Klug, Albert Hagège, Pascal Sabouraud, Arnaud Isapof, Julien Durigneux, Olivier Lascols, Pascal Laforêt, Armelle Magot, Ivana Dabaj, Eloi Marijon, Camille Vatier, Pascal Cintas, Emmanuelle Salort, Bénédicte Gaborit, Antoine Muchir, Xavier Ferrer, Pascale Richard, Corinne Metay, Stéphane Boulé, Sarah Leonard-Louis, Philippe Mabo, V. Tiffreau, Caroline Stalens, Jitendra K. Vohra, Stéphane Schaeffer, Khadija Chikhaoui, Eric Bieth, Sandra Mercier, Pierre Ambrosi, Aleksandra Nadaj-Pakleza, Michèle Mayer, Katja Zeppenfeld, Gisèle Bonne, Véronique Manel, Jean-Marc Davy, Guilhem Sole, Ghassan Moubarak, Nicolas Lamblin, Klaus Dieterich, Christophe Meune, Abdallah Fayssoil, Arnaud Lazarus, Philippe Maury, Karim Wahbi, Philippe Petiot, Isabelle Jéru, Annick Toutain, Corinne Vigouroux, Ana Ferreiro, Maud Michaud, H.M. Bécane, Bruno Eymard, Thomas D. Gossios, Marie-Christine Vantyghem, Saurabh Kumar, Estelle Gandjbakhch, Yann Péréon, T. Thompson, Marie-Christine Minot-Myhié, Anthony Behin, Frédéric Sacher, Philippe Charron, Nicolas Combes, Julien Praline, Dominique Babuty, Emmanuelle Lagrue, Usha B. Tedrow, Jean-Marc Sellal, Florence Petit, Perry M. Elliott, Frédéric Anselme, Philippe Chevalier, Frederic Taithe, Christine Barnerias, Vincent Laugel, Andoni Echaniz-Laguna, Raphaël P. Martins, Alexander F.A. Androulakis, Rabah Ben Yaou, Franck Boccara, Ulrike Walther-Louvier, Tanya Stojkovic, Françoise Bouhour, Annachiara De Sandre-Giovannoli, Susana Quijano-Roy, Françoise Chapon, Jean-Noël Trochu, Céline Tard, Anne Rollin, Jean-Marie Cuisset, Denis Duboc, Raphaël Porcher, Catherine Sarret, Jonathan M. Kalman, Florence Demurger, Damien Bonnet, Christine Francannet, Neal K. Lakdawala, Romain Eschalier, Fabien Labombarda, Kostantinos Savvatis, Raul Juntas Morales, Isabelle Desguerre, Nicolas Lévy, Anne-Claire Brehin, Service de Cardiologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Rouen, Normandie Université (NU), St Bartholomew's Hospital (London), Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Association française contre les myopathies (AFM-Téléthon), IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Service de Cardiologie B, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Hôpital Ambroise Paré [AP-HP], William Harvey Research Institute, Barts and the London Medical School, Biostatistique et épidemiologie clinique, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de cardiologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Filière Neuromusculaire (FILNEMUS), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Université de Caen Normandie (UNICAEN), Laboratoire d'Informatique Scientifique et Industrielle (LISI), Université de Poitiers-Ecole Nationale Supérieure de Mécanique et d'Aérotechnique [Poitiers] (ISAE-ENSMA), Hôpital Raymond Poincaré [AP-HP], CHU Lille, Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 (EGID), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Aix Marseille Université (AMU), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Institut de cardiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de cardiologie et maladies vasculaires [Rennes] = Cardiac, Thoracic, and Vascular Surgery [Rennes], CHU Pontchaillou [Rennes], Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Clinique Pasteur [Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), The Royal Melbourne Hospital, Leiden University Medical Center (LUMC), Universiteit Leiden, Service de neurologie pédiatrique [CHU Necker], Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Necker - Enfants Malades [AP-HP], Hôpital Privé Le Bois Ramsay Santé [Lille], Service de génétique [Rouen], Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Mobilités : Vieillissement, Pathologie, Santé (COMETE), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Roger Salengro [Lille], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre de ressources biologiques Tissus ADN Cellules [Hôpital de la Timone - APHM] (CRB TAC), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Cytogénétique et de Biologie Cellulaire, Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire [Grenoble] (CHU), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Les Hôpitaux Universitaires de Strasbourg (HUS), CHU Clermont-Ferrand, Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de neurologie [Bordeaux], Service de Génétique Médicale [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de chirurgie cadiovasculaire et thoracique [Rouen], Hôpital Charles Nicolle [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Service de cardiologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CHU Trousseau [APHP], Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Strasbourg, Clinique Ambroise Paré [Centres Médico-Chirurgicaux Ambroise Pré, Pierre Cherest, Hartmann], Hôpital Cochin [AP-HP], Hospices Civils de Lyon (HCL), Service de génétique médicale - Unité de génétique clinique [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Lorraine (UL), Service de neurologie [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Centre Hospitalier Universitaire de Reims (CHU Reims), Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Neurologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], Institut Cochin (IC UM3 (UMR 8104 / U1016)), Laboratoire d'étude de la motricité humaine - EA 3608 (LEMH), Université de Lille, Droit et Santé, Service de génétique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Physiopathologie et thérapie du muscle strié, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Montréal (UdeM), Laboratoire Génie des procédés papetiers (LGP2 ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS), The Heart Hospital [London], University College of London [London] (UCL), This study was funded by grants from the AFM-Téléthon (French Alliance against Myopathies), which was not involved in the design and conduct of the study, collection, management, analysis, and interpretation of the data, preparation, review, or approval of the manuscript, and decision to submit the manuscript for publication. Some of this work was undertaken at University College London (United Kingdom) and St. Bartholomew’s Hospital (London, United Kingdom), which received a portion of funding from the United Kingdom Department of Health’s National Institute for Health Research Biomedical Research Centres funding scheme., Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Centre de recherche en myologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP], CHU Bordeaux [Bordeaux]-Université Bordeaux Segalen - Bordeaux 2, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP], unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de cardiologie et maladies vasculaires, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], CHU Pitié-Salpêtrière [APHP], Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Unit of Neuromuscular Morphology [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [APHP]-Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre de référence des maladies rares neuromusculaires Aquitaine-Grand Sud Ouest, CHU Bordeaux [Bordeaux], Laboratoire d'Informatique Scientifique et Industrielle (LISI / ENSMA), LISI-ENSMA, Service de Biochimie-Génétique [Béclère], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Thérapie des maladies du muscle strié, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Cardiologie A, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'Endocrinologie et Métabolisme, Unité de Cardiologie et Soins Intensifs, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Service de Génétique [Purpan], CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Centre de Référence M3C Malformations Cardiaques Congénitales Complexes, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-PRES Sorbonne Paris Cité-CHU Necker - Enfants Malades [AP-HP], Hôpital neurologique, Centre Hospitalier Universitaire de Lille (CHU de Lille), Service Neurologie Pédiatrique, Service de Neuropédiatrie, INSERM U836, équipe 4, Muscles et pathologies, Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Département de Neurologie, Hôpital Civil de Strasbourg, Groupe Myologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de génétique médicale, CHU - HÔTEL-DIEU Clermont-Ferrand, CLAD Ouest, Centre Hospitalier Universitaire [Rennes], Centre recherche en CardioVasculaire et Nutrition (C2VN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de Neuropédiatrie [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie et cerveau, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement (Inserm U1167 - RID-AGE - Institut Pasteur), Clinique Ambroise Paré, CHU Cochin [AP-HP], Epilepsie, sommeil et explorations fonctionnelles neuropédiatriques, Hospices Civils de Lyon (HCL)-Hopital Neurologique-Hôpital Femme Mère Enfant, Department of Medicine, Columbia University [New York]-College of Physicians and Surgeons, Service de neurologie, Hospices Civils de Lyon (HCL)-Hôpital de la Croix-Rousse [CHU - HCL], Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc - U837 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université Lille 2 - Faculté de Médecine, Hôpital de Rangueil, Institut Pascal - Clermont Auvergne (IP), Sigma CLERMONT (Sigma CLERMONT)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), laboratoire d'étude de la motricité humaine (LEMH EA3608), Université de Montréal - UdeM (CANADA), Laboratoire Génie des procédés papetiers (LGP2), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche en Myologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-PRES Sorbonne Paris Cité-CHU Necker - Enfants Malades [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), European Genomic Institute for Diabetes - FR 3508 (EGID), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Hôpital Purpan [Toulouse], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Hôpital Gui de Chauliac [Montpellier]-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), SIGMA Clermont (SIGMA Clermont)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut de Myologie, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Tachycardia, medicine.medical_specialty, implantable, Accurate estimation, Ventricular Tachyarrhythmias, Validation Studies as Topic, 030204 cardiovascular system & hematology, tachycardia, Sudden death, LMNA, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, death, Physiology (medical), Internal medicine, defibrillators, medicine, Humans, In patient, 030212 general & internal medicine, sudden, [SDV.GEN]Life Sciences [q-bio]/Genetics, Prediction score, business.industry, Defibrillators, Implantable, ventricular, Tachycardia, Ventricular, Cardiology, Female, medicine.symptom, Cardiomyopathies, Cardiology and Cardiovascular Medicine, business
Abstract: Background: An accurate estimation of the risk of life-threatening (LT) ventricular tachyarrhythmia (VTA) in patients with LMNA mutations is crucial to select candidates for implantable cardioverter-defibrillator implantation. Methods: We included 839 adult patients with LMNA mutations, including 660 from a French nationwide registry in the development sample, and 179 from other countries, referred to 5 tertiary centers for cardiomyopathies, in the validation sample. LTVTA was defined as (1) sudden cardiac death or (2) implantable cardioverter defibrillator–treated or hemodynamically unstable VTA. The prognostic model was derived using the Fine-Gray regression model. The net reclassification was compared with current clinical practice guidelines. The results are presented as means (SD) or medians [interquartile range]. Results: We included 444 patients, 40.6 (14.1) years of age, in the derivation sample and 145 patients, 38.2 (15.0) years, in the validation sample, of whom 86 (19.3%) and 34 (23.4%) experienced LTVTA over 3.6 [1.0–7.2] and 5.1 [2.0–9.3] years of follow-up, respectively. Predictors of LTVTA in the derivation sample were: male sex, nonmissense LMNA mutation, first degree and higher atrioventricular block, nonsustained ventricular tachycardia, and left ventricular ejection fraction (https://lmna-risk-vta.fr). In the derivation sample, C-index (95% CI) of the model was 0.776 (0.711–0.842), and the calibration slope 0.827. In the external validation sample, the C-index was 0.800 (0.642–0.959), and the calibration slope was 1.082 (95% CI, 0.643–1.522). A 5-year estimated risk threshold ≥7% predicted 96.2% of LTVTA and net reclassified 28.8% of patients with LTVTA in comparison with the guidelines-based approach. Conclusions: In comparison with the current standard of care, this risk prediction model for LTVTA in laminopathies significantly facilitated the choice of candidates for implantable cardioverter defibrillators. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03058185.
Published: 2019

17. Spinal muscular atrophy with respiratory distress type 1: A multicenter retrospective study

Author: Maryse Magen, Susana Quijano-Roy, Domitille Gras, Mathilde Nizon, Corinne Magdelaine, Catherine Vanhulle, Fabienne Giuliano, Eric Bieth, Véronique Manel, Damien Haye, Pascal Cintas, Florence Petit, Klaus Dieterich, Agnès Viguier, S. Peudenier, Valérie Lauwers-Cances, Mélanie Fradin, Claude Cances, Isabelle Desguerre, Arnaud Isapof, Michèle Mathieu-Dramard, and Michaël Jokic
Subjects: Male, 0301 basic medicine, Artificial ventilation, Pediatrics, medicine.medical_specialty, medicine.medical_treatment, Diaphragmatic breathing, Muscular Atrophy, Spinal, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Respiratory system, Genetics (clinical), Retrospective Studies, Respiratory Distress Syndrome, Newborn, Palsy, Respiratory distress, business.industry, Infant, Newborn, Infant, Retrospective cohort study, Spinal muscular atrophy, Prognosis, medicine.disease, Respiration, Artificial, Hypotonia, DNA-Binding Proteins, Phenotype, 030104 developmental biology, Neurology, Child, Preschool, Mutation, Pediatrics, Perinatology and Child Health, Disease Progression, Female, France, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery, Transcription Factors
Abstract: Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a rare autosomal recessive neuromuscular disorder characterized by progressive motor and respiratory decline during the first year of life. Early and late-onset cases have recently been reported, although not meeting the established diagnostic criteria, these cases have been genotyped. We thus conducted a national multicenter observational retrospective study to determine the prognosis of children with SMARD1 according to their phenotype. We recorded all known French pediatric cases with mutations identified on the immunoglobulin μ-binding protein 2 gene and the presence of respiratory symptoms. Thirty centers provided 22 observations. A diaphragmatic palsy was diagnosed 1.5 months (p = 0.02) after first respiratory symptoms, and hypotonia preceded areflexia by 4 months (p = 0.02). Early onset of symptoms leading to specialist consultation before the age of 3 months was associated with a significantly worse prognosis (p
Published: 2019

18. JAK inhibitors are effective in a subset of patients with juvenile dermatomyositis: a monocentric retrospective study

Author: Christine Bodemer, Arnaud Isapof, Cyril Gitiaux, Mathieu P Rodero, Jean-Philippe Herbeuval, Florence Aeschlimann, Brigitte Bader-Meunier, Marie-Louise Frémond, Isabelle Melki, Jean-Luc Charuel, François-Jérôme Authier, Vincent Bondet, Pierre Quartier, Darragh Duffy, Tom Le Voyer, Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Human genetics of infectious diseases : Mendelian predisposition (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CHU Necker - Enfants Malades [AP-HP], Université Paris Cité (UPCité), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Département de pathologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de dermatologie [CHU Necker], Laboratory of neurogenetics and neuroinflammation (Equipe Inserm U1163), AP-HP Hôpital universitaire Robert-Debré [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service de Neuropédiatrie [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Immunologie Translationnelle - Translational Immunology lab, Institut Pasteur [Paris], Service d'Immunologie [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Institut Pasteur [Paris] (IP)
Subjects: Male, Ruxolitinib, medicine.medical_specialty, Adolescent, Disease, Gastroenterology, Dermatomyositis, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Refractory, Internal medicine, Nitriles, Medicine, Humans, Janus Kinase Inhibitors, Pharmacology (medical), Immunoadsorption, Child, Juvenile dermatomyositis, Janus kinase inhibitor, Autoantibodies, Janus Kinases, Retrospective Studies, 030203 arthritis & rheumatology, Sulfonamides, Muscle biopsy, medicine.diagnostic_test, business.industry, juvenile dermatomyositis, Interferon-alpha, type 1 interferon, Retrospective cohort study, medicine.disease, 3. Good health, Pyrimidines, Treatment Outcome, Janus-kinase inhibitor, Purines, Child, Preschool, Azetidines, Pyrazoles, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, business, 030217 neurology & neurosurgery, Biomarkers, medicine.drug
Abstract: Objective To evaluate the efficacy and safety of Janus kinase inhibitors (JAKis) in JDM. Methods We conducted a single-centre retrospective study of patients with JDM treated by JAKi with a follow-up of at least 6 months. Proportion of clinically inactive disease (CID) within 6 months of JAKi initiation was evaluated using PRINTO criteria and skin Disease Activity Score. Serum IFN-α concentration was measured by Simoa assay. Results Nine refractory and one new-onset patients with JDM treated with ruxolitinib (n = 7) or baricitinib (n = 3) were included. The main indications for treatment were refractory muscle involvement (n = 8) and ulcerative skin disease (n = 2). CID was achieved in 5/10 patients (two/two anti-MDA5, three/four anti-NXP2, zero/three anti-TIF1γ-positive patients) within 6 months of JAKi introduction. All responders could withdraw plasmatic exchange, immunoadsorption and other immunosuppressive drugs. The mean daily steroid dose decreased from 1.1 mg/kg (range 0.35–2 mg/kg/d) to 0.1 (range, 0–0.3, P = 0.008) in patients achieving CID, and was stopped in two. Serum IFN-α concentrations were elevated in all patients at the time of treatment initiation and normalized in both responder and non-responder. A muscle biopsy repeated in one patient 26 months after the initiation of JAKi, showed a complete restoration of muscle endomysial microvascular bed. Herpes zoster and skin abscesses developed in three and two patients, respectively. Conclusion JAKis resulted in a CID in a subset of new-onset or refractory patients with JDM and may dramatically reverse severe muscle vasculopathy. Overall tolerance was good except for a high rate of herpes zoster infection.
Published: 2021

19. PURA- Related Developmental and Epileptic Encephalopathy: Phenotypic and Genotypic Spectrum

Author: Dario Pruna, Theresa Grebe, Felippe Borlot, Michael J. Esser, Juan Pablo Appendino, Katherine L. Helbig, Elisa Ballardini, Casey Brew, Anne-Sophie Denommé-Pichon, Anne Ronan, Laurie A. Demmer, Usha Kini, Marta Somorai, Julie Vogt, Sébastien Moutton, Raffaella Faggioli, Julien Van-Gils, Davide Ognibene, Sara Olivotto, Sabine Grønborg, David Coman, David P. Bick, Guido Rubboli, Orrin Devinsky, Atiya S. Khan, Robyn Whitney, Christine Coubes, Caroline Nava, Karen Keough, SakkuBai R. Naidu, Lucio Giordano, Davide Colavito, Dominic Spadafore, Arnaud Isapof, Walla Al-Hertani, Antonio Vitobello, Andrea V. Andrade, Gaetano Cantalupo, Sandra Whalen, Boudewijn Gunning, Shanawaz Hussain, David Hunt, Nathan Noble, Bertrand Isidor, Beatriz Gamboni, Katrine M Johannesen, Julien Buratti, Stephanie Moortgat, Ida Cursio, Agnese Suppiej, Delphine Héron, Lía Mayorga, William Benko, Rahul Raman Singh, Cyril Mignot, Sotirios Keros, Aurore Garde, Nicola Foulds, Claudia A. L. Ruivenkamp, Elena Gardella, Barbara Scelsa, Fernanda Góes, Laurence Faivre, Richard J. Leventer, Ashley Collier, Farha Tokarz, Thomas Courtin, Klaas J. Wierenga, Xilma R. Ortiz-Gonzalez, Frédéric Tran-Mau-Them, Alejandra Mampel, Lynn Greenhalgh, Ashlea Franques, Amélie Piton, Felicia Varsalone, Marjolaine Willems, Alessandro Orsini, Diana Rodriguez, Clothilde Ormieres, Helen Stewart, Boris Keren, Austin Larson, Cathrine E. Gjerulfsen, Julie S. Cohen, Margot R.F. Reijnders, Mel Anderson, Shailesh Asakar, Rikke S. Møller, Alice Bonuccelli, Alexandra Afenjar, Claudio Graziano, Elaine Wirrell, Simona Damioli, Sangeetha Yoganathan, Devorah Segal, Ingo Helbig, Mindy H. Li, Rob P.W. Rouhl, Sarah Hicks, Allan Bayat, Holly Dubbs, Stefania Bigoni, Kelly Ratke, John Brandsema, Eva H. Brilstra, univOAK, Archive ouverte, The Danish Epilepsy Centre Filadelfia [Dianalund, Denmark], University of Southern Denmark (SDU), Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de référence Déficiences Intellectuelles de Causes Rares [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Mayo Clinic [Jacksonville], Département de pédiatrie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Hôpital d'Enfants [CHU Dijon], Hôpital du Bocage, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Equipe GAD (LNC - U1231), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques (LGMR), Université Montpellier 1 (UM1)-IFR3, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Department of Pediatrics [Univ California San Diego] (UC San Diego), School of Medicine [Univ California San Diego] (UC San Diego), University of California [San Diego] (UC San Diego), University of California (UC)-University of California (UC)-University of California [San Diego] (UC San Diego), University of California (UC)-University of California (UC), and University of Colorado Anschutz [Aurora]
Subjects: Pediatrics, medicine.medical_specialty, Socio-culturale, [SDV.GEN] Life Sciences [q-bio]/Genetics, Electroencephalography, Epilepsy, Developmental and Epileptic Encephalopathy, Intellectual disability, medicine, Genetics (clinical), feeding difficulties, [SDV.GEN]Life Sciences [q-bio]/Genetics, medicine.diagnostic_test, business.industry, fungi, medicine.disease, Hypotonia, Epileptic spasms, Neonatal hypotonia, neonatal hypotonia, Epilepsy syndromes, Cohort, epilepsy, Neurology (clinical), medicine.symptom, business
Abstract: Background and ObjectivesPurine-rich element-binding protein A (PURA) gene encodes Pur-α, a conserved protein essential for normal postnatal brain development. Recently, a PURA syndrome characterized by intellectual disability, hypotonia, epilepsy, and dysmorphic features was suggested. The aim of this study was to define and expand the phenotypic spectrum of PURA syndrome by collecting data, including EEG, from a large cohort of affected patients.MethodsData on unpublished and published cases were collected through the PURA Syndrome Foundation and the literature. Data on clinical, genetic, neuroimaging, and neurophysiologic features were obtained.ResultsA cohort of 142 patients was included. Characteristics of the PURA syndrome included neonatal hypotonia, feeding difficulties, and respiratory distress. Sixty percent of the patients developed epilepsy with myoclonic, generalized tonic-clonic, focal seizures, and/or epileptic spasms. EEG showed generalized, multifocal, or focal epileptic abnormalities. Lennox-Gastaut was the most common epilepsy syndrome. Drug refractoriness was common: 33.3% achieved seizure freedom. We found 97 pathogenic variants in PURA without any clear genotype-phenotype associations.DiscussionThe PURA syndrome presents with a developmental and epileptic encephalopathy with characteristics recognizable from neonatal age, which should prompt genetic screening. Sixty percent have drug-resistant epilepsy with focal or generalized seizures. We collected more than 90 pathogenic variants without observing overt genotype-phenotype associations.
Published: 2021

20. Genomic sequencing highlights the diverse molecular causes of Perrault syndrome: a peroxisomal disorder (PEX6), metabolic disorders (CLPP, GGPS1), and mtDNA maintenance/translation disorders (LARS2, TFAM)

Author: Sandra Whalen, Juliette Dupont, Sandrine Vuillaumier-Barrot, Chloe Hanna, Gorjana Robevska, Phillipa J. Lamont, Lurdes Sampaio, John Christodoulou, Rocio Rius, Elena J. Tucker, André Travessa, Jocelyn van den Bergen, Andrew H. Sinclair, Arnaud Isapof, Katrina M. Bell, Andrea Simpson, Jérôme Dulon, Sylvie Jaillard, Tanya Stojkovic, Susana Quijano-Roy, David R. Thorburn, Katie L. Ayers, Philippe Touraine, Murdoch Children's Research Institute (MCRI), University of Melbourne, CHU Pontchaillou [Rennes], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Filière Neuromusculaire (FILNEMUS), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), National Health and Medical Research Council (NHMRC)National Health and Medical Research Council of Australia [1113531], NHMRCNational Health and Medical Research Council of Australia [1074258, 1054432, 1062854, 1155244], CONACYTConsejo Nacional de Ciencia y Tecnologia (CONACyT), Victorian Government's Operational Infrastructure Support Program, Université d'Angers (UA)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: Adult, Male, Candidate gene, Adolescent, Mitochondrial translation, Hearing Loss, Sensorineural, [SDV]Life Sciences [q-bio], Gene Expression, Biology, DNA, Mitochondrial, Amino Acyl-tRNA Synthetases, Mitochondrial Proteins, 03 medical and health sciences, Peroxisomal disorder, Genetics, medicine, Peroxisomes, Farnesyltranstransferase, Humans, Genetic Predisposition to Disease, Child, Genetics (clinical), 030304 developmental biology, 0303 health sciences, Base Sequence, 030305 genetics & heredity, Ovary, High-Throughput Nucleotide Sequencing, Geranyltranstransferase, Endopeptidase Clp, TFAM, medicine.disease, Dimethylallyltranstransferase, Human genetics, Premature ovarian failure, Gonadal Dysgenesis, 46,XX, Pedigree, DNA-Binding Proteins, Protein prenylation, ATPases Associated with Diverse Cellular Activities, Female, PEX6, Transcription Factors
Abstract: International audience; Perrault syndrome is a rare heterogeneous condition characterised by sensorineural hearing loss and premature ovarian insufficiency. Additional neuromuscular pathology is observed in some patients. There are six genes in which variants are known to cause Perrault syndrome; however, these explain only a minority of cases. We investigated the genetic cause of Perrault syndrome in seven affected individuals from five different families, successfully identifying the cause in four patients. This included previously reported and novel causative variants in known Perrault syndrome genes, CLPP and LARS2, involved in mitochondrial proteolysis and mitochondrial translation, respectively. For the first time, we show that pathogenic variants in PEX6 can present clinically as Perrault syndrome. PEX6 encodes a peroxisomal biogenesis factor, and we demonstrate evidence of peroxisomal dysfunction in patient serum. This study consolidates the clinical overlap between Perrault syndrome and peroxisomal disorders, and highlights the need to consider ovarian function in individuals with atypical/mild peroxisomal disorders. The remaining patients had variants in candidate genes such as TFAM, involved in mtDNA transcription, replication, and packaging, and GGPS1 involved in mevalonate/coenzyme Q(10) biosynthesis and whose enzymatic product is required for mouse folliculogenesis. This genomic study highlights the diverse molecular landscape of this poorly understood syndrome.
Published: 2020

21. Congenital immobility and stiffness related to biallelic ATAD1 variants

Author: Sandra Chantot-Bastaraud, Lydie Burglen, Delphine Héron, Pierre-Louis Léger, Marie-Charlotte Villy, Julien Buratti, Diana Rodriguez, Arnaud Isapof, Diane Doummar, Isabelle Martin, Boris Keren, Alexandra Afenjar, M. Mayer, François Kieffer, Cyril Mignot, Sandra Whalen, Kim Maincent, Thierry Billette de Villemeur, Roxane Bunod, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0303 health sciences, Pathology, medicine.medical_specialty, business.industry, Spontaneous movements, [SDV]Life Sciences [q-bio], Phenotype, Article, Hypoventilation, 03 medical and health sciences, 0302 clinical medicine, Medicine, Hypertonia, In patient, Neurology (clinical), Hyperekplexia, Brainstem, medicine.symptom, business, Exome, 030217 neurology & neurosurgery, Genetics (clinical), 030304 developmental biology
Abstract: ObjectiveTo delineate the phenotype associated with biallelic ATAD1 variants.MethodsWe describe 2 new patients with ATAD1-related disorder diagnosed by whole-exome sequencing and compare their phenotype to 6 previous patients.ResultsPatients 1 and 2 had a similar distinctive phenotype comprising congenital stiffness of limbs, absent spontaneous movements, weak sucking, and hypoventilation. Both had absent brainstem evoked auditory responses (BEARs). Patient 1 carried the homozygous p.(His357Argfs*15) variant in ATAD1. In the light of the finding in patient 1, a second reading of exome data for patient 2 revealed the novel homozygous p.(Gly128Val) variant.ConclusionsAnalysis of the phenotypes of these 2 patients and of the 6 previous cases showed that biallelic ATAD1 mutations are responsible for a unique congenital encephalopathy likely comprising absent BEAR, different from hyperekplexia and other conditions with neonatal hypertonia.
Published: 2020

22. Effects of nusinersen after one year of treatment in 123 children with SMA type 1 or 2: a French real-life observational study

Author: Brigitte Chabrol, Pierre Beze-Beyrie, Vincent Laugel, Carole Vuillerot, Anne-Laude Avice, Delphine Bernoux, Anne Perville, Cecilia Altuzarra, Christine Barnerias, Emmanuelle Lagrue, Paola Ramirez-Garcia, Catherine Sarret, Catherine Vanhulle, Jean-Marie Cuisset, Susana Quijano-Roy, Vanessa Pauly, Juliette Ropars, Caroline Espil-Taris, Frédérique Audic, Claude Cances, Julien Durigneux, Isabelle Desguerre, Arnaud Isapof, Hervé Testard, Mondher Chouchane, Marta Gomez Garcia de la Banda, Pascal Sabouraud, Valérie Trommsdorff, Ulrike Walther-Louvier, Christian Richelme, Institut Pascal (IP), and SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS)
Subjects: Pediatrics, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Oligonucleotides, lcsh:Medicine, Spinal muscular atrophy type I, Spinal Muscular Atrophies of Childhood, Motor function measure, MFM, Muscular Atrophy, Spinal, 03 medical and health sciences, 0302 clinical medicine, Nusinersen, Humans, Medicine, Pharmacology (medical), 030212 general & internal medicine, Child, ComputingMilieux_MISCELLANEOUS, Genetics (clinical), Motor skill, Retrospective Studies, [SDV.GEN]Life Sciences [q-bio]/Genetics, business.industry, Research, lcsh:R, Significant difference, Infant, General Medicine, Spinal muscular atrophy, Motor neuron, SMA, Spinal cord, medicine.disease, 3. Good health, Spinal muscular atrophy type II, medicine.anatomical_structure, Observational study, France, business, 030217 neurology & neurosurgery
Abstract: Background Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord. Nusinersen has been covered by public healthcare in France since May 2017. The aim of this article is to report results after 1 year of treatment with intrathecal nusinersen in children with SMA types 1 and 2 in France. Comparisons between treatment onset (T0) and after 1 year of treatment (Y1) were made in terms of motor function and need for nutritional and ventilatory support. Motor development milestone achievements were evaluated using the modified Hammersmith Infant Neurologic Examination–Part 2 (HINE-2) for patients under 2 years of age and Motor Function Measure (MFM) scores for patients over 2 years of age. Results Data on 204 SMA patients (type 1 or 2) were retrospectively collected from the 23 French centers for neuromuscular diseases. One hundred and twenty three patients had been treated for at least 1 year and were included, 34 of whom were classified as type 1 (10 as type 1a/b and 24 as type 1c) and 89 as type 2. Survival motor Neuron 2 (SMN2) copy numbers were available for all but 6 patients. Patients under 2 years of age (n = 30), had significantly higher HINE-2 scores at year 1 than at treatment onset but used more nutritional and ventilatory support. The 68 patients over 2 years of age evaluated with the Motor Function Measure test had significantly higher overall scores after 1 year, indicating that their motor function had improved. The scores were higher in the axial and proximal motor function (D2) and distal motor function (D3) parts of the MFM scale, but there was no significant difference for standing and transfer scores (D1). No child in either of the two groups achieved walking. Conclusion Nusinersen offers life-changing benefits for children with SMA, particularly those with more severe forms of the disorder. Caregiver assessments are positive. Nevertheless, patients remain severely disabled and still require intensive support care. This new treatment raises new ethical challenges.
Published: 2020

23. COLLAGEN RELATED MUSCLE DISEASES

Author: Y. Elaribi, K. Benistan, F. Jobic, Florence Demurger, Marie-Christine Nougues, Jean-Marie Cuisset, A. Afenjar, Arnaud Isapof, Sandra Whalen, Vincent Laugel, Corinne Metay, Valérie Jobic, Christine Barnerias, Ana Ferreiro, Isabelle Desguerre, A. Benezit, J. Davion, S. Quijano, Judith Melki, and P. Richard
Subjects: Neurology, Pediatrics, Perinatology and Child Health, Neurology (clinical), Genetics (clinical)
Published: 2021

24. How chromosomal deletions can unmask recessive mutations? Deletions in 10q11.2 associated with CHAT or SLC18A3 mutations lead to congenital myasthenic syndrome

Author: Jean-Pierre Siffroi, Solveig Heide, Alexandra Afenjar, Damien Sternberg, Arnaud Isapof, Mathias Schwartz, Sandra Whalen, Marie-France Portnoï, Boris Keren, Sandra Chantot-Bastaraud, Brigitte Chabrol, Service de génétique et embryologie médicales [CHU Trousseau], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Biochimie Métabolique et Centre de Génétique moléculaire et chromosomique [CHU Pitié Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de Neuropédiatrie [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Hôpital de la Timone [CHU - APHM] (TIMONE), Service de Génétique médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Couvet, Sandrine, UF de Génétique chromosomique [CHU Trousseau], Maladies génétiques d'expression pédiatrique [CHU Trousseau] (Inserm U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], and UF Neurométabolique Bioclinique et Génétique [CHU Pitié-Salpêtrière]
Subjects: Male, 0301 basic medicine, choline acetyl-transferase, [SDV]Life Sciences [q-bio], Vesicular Acetylcholine Transport Proteins, MESH: Amino Acid Sequence, single nucleotide polymorphisms array, Congenital myasthenia, 0302 clinical medicine, MESH: In Situ Hybridization, Fluorescence, In Situ Hybridization, Fluorescence, Genetics (clinical), MESH: Genetic Association Studies, Oligonucleotide Array Sequence Analysis, MESH: Choline O-Acetyltransferase, Genetics, MESH: Polymorphism, Single Nucleotide, Congenital myasthenic syndrome, MESH: Infant, Choline acetyltransferase, Phenotype, [SDV] Life Sciences [q-bio], Female, Chromosome Deletion, compound heterozygoty, MESH: Myasthenic Syndromes, Congenital, vesicular acetyl-choline transporter, MESH: Mutation, MESH: Chromosome Deletion, Genes, Recessive, Locus (genetics), Single-nucleotide polymorphism, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Biology, MESH: Phenotype, Polymorphism, Single Nucleotide, DNA sequencing, Choline O-Acetyltransferase, 03 medical and health sciences, medicine, Humans, Amino Acid Sequence, Gene, MESH: Genes, Recessive, Genetic Association Studies, Myasthenic Syndromes, Congenital, MESH: Humans, MESH: Vesicular Acetylcholine Transport Proteins, Chromosomes, Human, Pair 10, Infant, medicine.disease, MESH: Male, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, MESH: Chromosomes, Human, Pair 10, MESH: Oligonucleotide Array Sequence Analysis, Mutation, MESH: Female, 030217 neurology & neurosurgery
Abstract: International audience; A congenital myasthenia was suspected in two unrelated children with very similar phenotypes including several episodes of severe dyspnea. Both children had a 10q11.2 deletion revealed by Single Nucleotide Polymorphisms array or by Next Generation Sequencing analysis. The deletion was inherited from the healthy mother in the first case. These deletions unmasked a recessive mutation at the same locus in both cases, but in two different genes: CHAT and SLC18A3.
Published: 2017

25. MYASTHENIA & RELATED DISORDERS

Author: X. Latypova, Bertrand Fontaine, Fanny Laffargue, Céline Buon, S. Bauche, Julien Fauré, Alain Sureau, Arnaud Isapof, John Rendu, A. Bernabe Gelot, Damien Sternberg, Denis Furling, Bruno Eymard, Julien Messéant, M. Mayer, Marie-Christine Nougues, Myriam Boëx, and Laure Strochlic
Subjects: Neurology, Pediatrics, Perinatology and Child Health, Neurology (clinical), Genetics (clinical)
Published: 2020

26. Polyhandicap and aging

Author: E. Laracca, J. Nouet, Cécile Freihuber, M. Ardati, M.C. Rousseau, Stéphanie Valence, E. Grimont, M. Valkov, Anderson Loundou, D. Willocq, Agnès Felce, P. Sellier, S. Amalou, S. Lenormand, Diane Doummar, C. Brisse, Karine Baumstarck, J.C. Grasset, S. Haddadou, A. Belorgey, K. Maincent, M. Gaulard, M.H. Phan, Sherezad Khaldi-Cherif, J. Teulade, S. Delvert, Diana Rodriguez, J. Bonheur, Stéphane Pietra, V. Aynie, P. Julien, Arnaud Isapof, C. Coiffier, L. Luciani, Alexandra Afenjar, M.-L. Moutard, M.-C. Nougues, Bénédicte Héron, H. Si Abdelkader, Pascal Auquier, S. Mathieu, Thierry Billette de Villemeur, I. Kammache, Tanguy Leroy, Fédération des hôpitaux de polyhandicap et multihandicap hôpital San Salvadour, Assistance publique-Hôpitaux de Paris, Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), and Aix Marseille Université (AMU)
Subjects: Gerontology, Adult, Male, Aging, Adolescent, medicine.medical_treatment, Health Status, Longevity, macromolecular substances, Comorbidity, Rehabilitation Centers, Severity of Illness Index, Residential Facilities, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Elderly persons, medicine, Humans, Disabled Persons, 030212 general & internal medicine, Curative care, ComputingMilieux_MISCELLANEOUS, Aged, Natural course, Rehabilitation, business.industry, Intellectual impairment, Public Health, Environmental and Occupational Health, Age Factors, Infant, General Medicine, Middle Aged, medicine.disease, Gastrostomy, 3. Good health, Cross-Sectional Studies, Neurodevelopmental Disorders, Etiology, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Nervous System Diseases, business, 030217 neurology & neurosurgery
Abstract: Background Knowledge of the health status and care management of elderly individuals with polyhandicap* is lacking; however, a better understanding of the natural course of ageing in persons with severe and complex disability would help optimize preventive and curative care management strategies. Objectives To describe persons with severe and complex disability aged 18–68 years by providing i) a description of their health status and ii) a description of their medications, medical devices and rehabilitation procedures. Methods This was an 18-month cross-sectional study including people aged 18–68 years with a combination of severe motor deficiency and profound intellectual impairment. They were recruited from 4 specialized rehabilitation centres, 9 residential facilities, and a neurological department. The following data were collected: aetiology of severe and complex disability, health status, medical devices, and rehabilitation procedures. Results A total of 474 persons with severe and complex disability were included (N = 219 [18–34 years], N = 151 [35–49 years], N = 104 [50–68] years). The aetiology of severe and complex disability was unknown for 13%–17% of persons with severe and complex disability across the 3 age classes. Behavioural disorders and pain were more frequent in the oldest age classes. Elderly persons with severe and complex disability had more severe but less unstable severe and complex disability. Their neurodevelopmental was close to that of a 4-month-old child without progression across age. Gastrostomy was the most frequent device needed by the persons with severe and complex disability. Conclusions The longevity of persons with severe and complex disability is improving; some of these persons, among whom are the least unstable and with less comorbidity, can survive for more than 50 years due to the improvement of preventive actions and supportive care.
Published: 2019

27. A large multicenter study of pediatric myotonic dystrophy type 1 for evidence-based management

Author: Hubert Journel, Sylvie Ragot-Mandry, Delphine Héron, Brigitte Chabrol, S. Peudenier, Jean-Marie Cuisset, Guillaume Bassez, Pascal Sabouraud, Catherine Sarret, Claude Cances, Mélanie Fradin, Agnès Jacquin-Piques, Julie Perrier-Boeswillald, Isabelle Desguerre, Michèle Mayer, Susana Quijano-Roy, Arnaud Isapof, Vincent Laugel, Marie De Antonio, Frédérique Audic, Nathalie Bach, Emmanuelle Lagrue, C. Espil, Rémi Bellance, Catherine Vanhulle, Armelle Magot, Hervé Testard, Julien Durigneux, Yann Péréon, Cécile Laroche-Raynaud, Romain K. Gherardi, Christine Barnerias, Céline Dogan, Véronique Manel, François Rivier, Dalil Hamroun, Ulrike Walther-Louvier, Christian Richelme, Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de neurologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Necker - Enfants Malades [AP-HP], Département de Pédiatrie [CHU Toulouse], CHU Toulouse [Toulouse], Service de Neurologie Pédiatrique, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre de Référence des Maladies Héréditaires du Métabolisme, Service de neurométabolisme, Service de neuropédiatrie, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service de génétique clinique [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-hôpital Sud, Groupe de recherche clinique 'déficience intellectuelle et autisme', Université Pierre et Marie Curie - Paris 6 (UPMC), Service de Neuropédiatrie [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Pontchaillou [Rennes], Hôpital de Hautepierre [Strasbourg], Laboratoire d'Explorations Fonctionnelles, Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), Service de neurologie pédiatriques et maladies du dévéloppement, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Atlantic Gene Therapies, Service de Pédiatrie, Rééducation et Réanimation Neurorespiratoire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Raymond Poincaré [AP-HP], Service de pédiatrie, Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital l'Archet, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), American Memorial Hospital (Reims), Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), CHU Grenoble, Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Service d'histologie-Hôpital Henri Mondor, Imagerie et cerveau, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), AP-HP, Paris-CHU Necker - Enfants Malades [AP-HP], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-Hôpital Sud, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Service de neuropédiatrie [Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP Hôpital Raymond Poincaré [Garches], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut Pascal - Clermont Auvergne (IP), Sigma CLERMONT (Sigma CLERMONT)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Myologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), SIGMA Clermont (SIGMA Clermont)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), École Pratique des Hautes Études (EPHE), Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Rennes (UR)-CHU Pontchaillou [Rennes]-hôpital Sud, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: 0301 basic medicine, Foot Deformities, Male, Pediatrics, medicine.medical_specialty, Adolescent, Myotonic dystrophy, Severity of Illness Index, 03 medical and health sciences, 0302 clinical medicine, Genotype-phenotype distinction, Cataracts, Severity of illness, medicine, Humans, Myotonic Dystrophy, Registries, Child, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Evidence-Based Medicine, Muscle Weakness, business.industry, Infant, Newborn, Evidence-based management, Infant, Cardiorespiratory fitness, Arrhythmias, Cardiac, Evidence-based medicine, medicine.disease, 3. Good health, 030104 developmental biology, Multicenter study, Child, Preschool, Cohort, Autism, Female, Neurology (clinical), France, business, Respiratory Insufficiency, Trinucleotide Repeat Expansion, 030217 neurology & neurosurgery
Abstract: ObjectiveTo genotypically and phenotypically characterize a large pediatric myotonic dystrophy type 1 (DM1) cohort to provide a solid frame of data for future evidence-based health management.MethodsAmong the 2,697 patients with genetically confirmed DM1 included in the French DM-Scope registry, children were enrolled between January 2010 and February 2016 from 24 centers. Comprehensive cross-sectional analysis of most relevant qualitative and quantitative variables was performed.ResultsWe studied 314 children (52% females, with 55% congenital, 31% infantile, 14% juvenile form). The age at inclusion was inversely correlated with the CTG repeat length. The paternal transmission rate was higher than expected, especially in the congenital form (13%). A continuum of highly prevalent neurodevelopmental alterations was observed, including cognitive slowing (83%), attention deficit (64%), written language (64%), and spoken language (63%) disorders. Five percent exhibited autism spectrum disorders. Overall, musculoskeletal impairment was mild. Despite low prevalence, cardiorespiratory impairment could be life-threatening, and frequently occurred early in the first decade (25.9%). Gastrointestinal symptoms (27%) and cataracts (7%) were more frequent than expected, while endocrine or metabolic disorders were scarce.ConclusionsThe pedDM-Scope study details the main genotype and phenotype characteristics of the 3 DM1 pediatric subgroups. It highlights striking profiles that could be useful in health care management (including transition into adulthood) and health policy planning.
Published: 2019

28. Muscle ischaemia associated with NXP2 autoantibodies: a severe subtype of juvenile dermatomyositis

Author: François-Jérôme Authier, Guillaume Bassez, Romain K. Gherardi, Christine Barnerias, Isabelle Melki, Pierre Quartier, Jessie Aouizerate, Cyril Gitiaux, Arnaud Isapof, Jean-Luc Charuel, Isabelle Desguerre, Brigitte Bader-Meunier, Marie De Antonio, and Christine Bodemer
Subjects: Male, medicine.medical_specialty, Multivariate analysis, Biopsy, Gastroenterology, Severity of Illness Index, Dermatomyositis, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Ischemia, Internal medicine, Severity of illness, medicine, Humans, Pharmacology (medical), Muscle, Skeletal, Juvenile dermatomyositis, Autoantibodies, 030203 arthritis & rheumatology, Adenosine Triphosphatases, medicine.diagnostic_test, business.industry, Autoantibody, Muscle weakness, medicine.disease, DNA-Binding Proteins, Cohort, Disease Progression, Female, medicine.symptom, business, 030217 neurology & neurosurgery, Biomarkers, Follow-Up Studies
Abstract: Objectives Myositis-specific autoantibodies (MSAs) are increasingly used to delineate distinct subgroups of JDM. The aim of our study was to explore without a priori hypotheses whether MSAs are associated with distinct clinical-pathological changes and severity in a monocentric JDM cohort. Methods Clinical, biological and histological findings from 23 JDM patients were assessed. Twenty-six histopathological parameters were subjected to multivariate analysis. Results Autoantibodies included anti-NXP2 (9/23), anti-TIF1γ (4/23), anti-MDA5 (2/23), no MSAs (8/23). Multivariate analysis yielded two histopathological clusters. Cluster 1 (n = 11) showed a more severe and ischaemic pattern than cluster 2 (n = 12) assessed by: total score severity ⩾ 20 (100.0% vs 25.0%); visual analogic score ⩾6 (100.0% vs 25.0%); the vascular domain score >1 (100.0% vs 41.7%); microinfarcts (100% vs 58.3%); ischaemic myofibrillary loss (focal punched-out vacuoles) (90.9 vs 25%); and obvious capillary loss (81.8% vs 16.7). Compared with cluster 2, patients in cluster 1 had strikingly more often anti-NXP2 antibodies (7/11 vs 2/12), more pronounced muscle weakness, more gastrointestinal involvement and required more aggressive treatment. Furthermore, patients with anti-NXP2 antibodies, mostly assigned in the first cluster, also displayed more severe muscular disease, requiring more aggressive treatment and having a lower remission rate during the follow-up period. Conclusion Marked muscle ischaemic involvement and the presence of anti-NXP2 autoantibodies are associated with more severe forms of JDM.
Published: 2017

29. Isolated corpus callosum agenesis: a ten-year follow-up after prenatal diagnosis (How are the children without corpus callosum at 10 years of age?)

Author: Jean-Michel Baron, Thierry Billette de Villemeur, Catherine Adamsbaum, Arnaud Isapof, Josué Feingold, Antoinette Gelot, François Kieffer, Marie-Laure Moutard, Virginie Kieffer, and Fanny Lewin
Subjects: Pregnancy, Pediatrics, medicine.medical_specialty, business.industry, Corpus Callosum Agenesis, Neuropsychology, Fetal alcohol syndrome, Obstetrics and Gynecology, Prenatal diagnosis, medicine.disease, Corpus callosum, Epilepsy, Borderline intellectual functioning, Medicine, business, Genetics (clinical)
Abstract: Background Corpus callosum agenesis (CCA) is generally diagnosed in utero. Outcome appears to be better if the malformation is isolated. The aim of this study, which is the first one with a long (10 years) and standardized follow up, was to report cognitive abilities of children with isolated CCA diagnosed prenatally. Methods We prospectively evaluated 17 children. Clinical examinations, neuropsychological tests were performed each year. School achievement and personal and familial data were collected. Results Twelve children completed the entire follow up. One child was finally considered to have associated CCA, because signs of fetal alcohol syndrome had become obvious. Of the 11 other children, three (27%) had borderline intelligence whereas the intelligence levels of eight (73%) were in the normal range, although half of these children experienced some difficulties in scholastic achievement. Neither epilepsy nor intellectual deficiency was noted and intellectual quotient scores correlated strongly with the mother's education level. Conclusion Although prenatal diagnosis of isolated CCA is reliable, false postnatal diagnoses remain possible (10–20%) even with complete prenatal screening. Outcome is mostly favorable because intelligence is within the normal range for nearly 3/4 of the children. However, they frequently have mild learning difficulties. © 2012 John Wiley & Sons, Ltd.
Published: 2012

30. Klüver Bucy syndrome following hypoglycaemic coma in a patient with glycogen storage disease type Ib

Author: Philippe Labrune, Vincent Gajdos, Alix Mollet Boudjemline, Arnaud Isapof, François Petit, and Jean-Bernard Witas
Subjects: Adult, Blood Glucose, Male, medicine.medical_specialty, Pediatrics, Treatment outcome, Glycogen Storage Disease Type I, Klüver–Bucy syndrome, Severity of Illness Index, Internal medicine, Severity of illness, Glycogen Storage Disease Type Ib, Genetics, medicine, Humans, Coma, Respiratory Tract Infections, Genetics (clinical), Hypoglycaemic coma, Blindness, business.industry, Respiratory infection, Fasting, medicine.disease, Magnetic Resonance Imaging, Hypoglycemia, Treatment Outcome, Endocrinology, Type I glycogen storage disease, Kluver-Bucy Syndrome, business, Biomarkers
Abstract: Patients with type I glycogen storage disease (GSD) have poor tolerance to fasting, sometimes less than 3 hours during infancy. Even though most patients are able, as they get older, to tolerate a longer fasting period, they are at permanent risk for fast-induced hypoglycaemia, even in adulthood. Klüver Bucy syndrome, is characterized by psychic blindness (inability to recognize familiar objects), hypermetamorphosis (strong tendency to react to visual stimulus), increased oral exploration, placidity, indiscriminate hyper-sexuality and change in dietary habits. In this case report, we describe the development of Klüver Bucy syndrome in a 28-year-old man with type Ib GSD, following prolonged and severe hypoglycaemia triggered by a common respiratory infection.
Published: 2010

31. Impact du dépistage anténatal des agénésies du corps calleux sur le devenir des grossesses. Étude de 155 dossiers de 2000 à 2006

Author: T. Billette de Villemeur, Catherine Garel, E. Raffo, M.-L. Moutard, S. Sacco, Arnaud Isapof, Fanny Lewin, Catherine Adamsbaum, J.-M. Jouannic, Antoinette Gelot, and Virginie Kieffer
Subjects: Gynecology, Fetus, medicine.medical_specialty, Pregnancy, business.industry, Corpus Callosum Agenesis, Prenatal diagnosis, Retrospective cohort study, Abortion, medicine.disease, El Niño, parasitic diseases, Pediatrics, Perinatology and Child Health, Gestation, Medicine, business
Abstract: The purpose of this study was to investigate the changes between 2000 and 2006 in pregnancy outcome when a diagnosis of either isolated or associated fetal corpus callosum agenesis (CCA) was made, given that beginning in 2003, the information provided to couples facing this problem related a good prognosis in nearly 80 % of cases of isolated CCA and a poor prognosis in 20 % of cases. We retrospectively analyzed all pregnancies with a fetal diagnosis of CCA between 2000 and 2006 (n=155) and compared two periods: the first group from 2000 to June 2003, the second from July 2003 to 2006. For each group, we analyzed the type of CCA during pregnancy - either isolated or associated - and the outcome of pregnancy. We compared the rate of pregnancy termination before and after 2003 and analyzed the accuracy of the prenatal CCA diagnosis. Of the 155 patients studied, 62 terminated the pregnancy. The overall rate of termination decreased from 31/70 to 31/85. When CCA was said to be isolated prenatally, the rate of pregnancy termination fell from 13/35 to 9/44 (-17 %) (p
Published: 2010

32. Gross proteinuria post transplant in a child with nephrotic syndrome of the Finnish type--mechanical vs immunological pathogenesis

Author: Jérémy Raynot, Tim Ulinski, Marion Lenoir, Albert Bensman, Monique Pressac, Laurence Ross-Cerdan, Béatrice Letavernier, Georges Deschênes, Fleur Lorton, Arnaud Isapof, Hanna Debiec, and Christine Grapin
Subjects: medicine.medical_specialty, Pathology, Nephrotic Syndrome, Nephrosis, Nephrin, Pathogenesis, Recurrence, Internal medicine, medicine, Humans, Transplantation, Proteinuria, biology, business.industry, Infant, Glomerulonephritis, medicine.disease, Kidney Transplantation, Endocrinology, Nephrology, In utero, biology.protein, Slit diaphragm, Female, medicine.symptom, business, Nephrotic syndrome
Abstract: Nephrotic syndrome of the Finnish type (NSF) is anautosomal-recessive disorder, characterized by massiveproteinuria in utero and nephrosis at birth. NSF iscaused by mutations in the NPHS1 gene which codesfor nephrin [1], a cell adhesion molecule specificallylocalized at the slit diaphragm of the glomerularbasement membrane [2]. Mutations, such as Fin
Published: 2006

33. Isolated corpus callosum agenesis: a ten-year follow-up after prenatal diagnosis (how are the children without corpus callosum at 10 years of age?)

Author: Marie-Laure, Moutard, Virginie, Kieffer, Josué, Feingold, Fanny, Lewin, Jean-Michel, Baron, Catherine, Adamsbaum, Antoinette, Gélot, Arnaud, Isapof, François, Kieffer, and Thierry Billette, de Villemeur
Subjects: Male, Intelligence, Age Factors, Infant, Newborn, Infant, Neuropsychological Tests, Ultrasonography, Prenatal, Child Development, Motor Skills, Pregnancy, Intellectual Disability, Educational Status, Humans, Female, Agenesis of Corpus Callosum, Child, Follow-Up Studies
Abstract: Corpus callosum agenesis (CCA) is generally diagnosed in utero. Outcome appears to be better if the malformation is isolated. The aim of this study, which is the first one with a long (10 years) and standardized follow up, was to report cognitive abilities of children with isolated CCA diagnosed prenatally.We prospectively evaluated 17 children. Clinical examinations, neuropsychological tests were performed each year. School achievement and personal and familial data were collected.Twelve children completed the entire follow up. One child was finally considered to have associated CCA, because signs of fetal alcohol syndrome had become obvious. Of the 11 other children, three (27%) had borderline intelligence whereas the intelligence levels of eight (73%) were in the normal range, although half of these children experienced some difficulties in scholastic achievement. Neither epilepsy nor intellectual deficiency was noted and intellectual quotient scores correlated strongly with the mother's education level.Although prenatal diagnosis of isolated CCA is reliable, false postnatal diagnoses remain possible (10-20%) even with complete prenatal screening. Outcome is mostly favorable because intelligence is within the normal range for nearly 3/4 of the children. However, they frequently have mild learning difficulties.
Published: 2012

34. Frequency and natural history of sarcoglycanopathies in Paris neuromuscular centers

Author: Brigitte Estournet, F. Leturcq, Claudio Semplicini, Arnaud Isapof, Sarah Leonard-Louis, P. Laforêt, Isabelle Desguerre, Anthony Behin, Bruno Eymard, M. Mayer, Christine Barnerias, Raquel Guimarães-Costa, and T. Stojkovic
Subjects: Natural history, Gerontology, Neurology, business.industry, Pediatrics, Perinatology and Child Health, Medicine, Neurology (clinical), business, Genetics (clinical), Sarcoglycanopathies
Published: 2015

35. SFP CO-08 - Amélioration de l’epilepsie et progrès psychomoteurs d’une enfant atteinte de maladie de Gaucher type 3 sous traitement par molécule chaperone

Author: J. Bonheur, Diana Rodriguez, Arnaud Isapof, Bénédicte Héron, and T. Billette de Villemeur
Subjects: Pediatrics, Perinatology and Child Health
Abstract: Objectif La maladie de Gaucher est une accumulation de glucosylceramide dans les lysosomes due a la mutation du gene codant pour la betaglucocerebrosidase. Le type 3 est marque par une atteinte cerebrale progressive dont une epilepsie myoclonique. Plusieurs cas d’amelioration de l’epilepsie apres traitement par molecule chaperone de la betaglucocerebrosidase, l’ambroxol, sont rapportes dans la litterature adulte. Sujet Une petite fille de 6 ans atteinte du type 3, avec une epilepsie pharmacoresistante sous quadritherapie et enzymotherapie substitutive, presente une regression psychomotrice depuis mars 2013, des etats de mal epileptiques plurimensuels et des myoclonies incessantes. Resultat En juillet, devant l’aggravation clinique, un traitement par ambroxol est introduit. A 2 mois, il n’y a plus de crise d’epilepsie. A 3 mois, une amelioration de l’eveil, de la motricite et des myoclonies est notee, avec une persistance des effets benefiques a 6 mois. Une video avant et apres traitement sera presentee. Conclusion Cette observation montre l’interet therapeutique de l’ambroxol associe a l’enzymotherapie dans la maladie de Gaucher de type 3 avec epilepsie myoclonique progressive. Cela doit etre confirme sur le long terme par des essais cliniques prospectifs.
Published: 2014

36. Les chorées d’apparition aiguë ou subaiguë chez l’enfant : étude de 35 enfants (vidéo)

Author: Arnaud Isapof, Domitille Gras, Bénédicte Héron, T. Billette de Villemeur, Diana Rodriguez, Cécile Laroche, Jacques Motte, Diane Doummar, Kim Maincent, and Agathe Roubertie
Subjects: Pediatrics, Perinatology and Child Health
Published: 2013

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