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Item does not contain fulltext Jansen-de Vries syndrome (JdVS) is a neurodevelopmental condition attributed to pathogenic variants in Exons 5 and 6 of PPM1D. As the full phenotypic spectrum and natural history remain to be defined, we describe a large cohort of children and adults with JdVS. This is a retrospective cohort study of 37 individuals from 34 families with disease-causing variants in PPM1D leading to JdVS. Clinical data were provided by treating physicians and/or families. Of the 37 individuals, 27 were male and 10 female, with median age 8.75 years (range 8 months to 62 years). Four families document autosomal dominant transmission, and 32/34 probands were diagnosed via exome sequencing. The facial gestalt, including a broad forehead and broad mouth with a thin and tented upper lip, was most recognizable between 18 and 48 months of age. Common manifestations included global developmental delay (35/36, 97%), hypotonia (25/34, 74%), short stature (14/33, 42%), constipation (22/31, 71%), and cyclic vomiting (6/35, 17%). Distinctive personality traits include a hypersocial affect (21/31, 68%) and moderate-to-severe anxiety (18/28, 64%). In conclusion, JdVS is a clinically recognizable neurodevelopmental syndrome with a characteristic personality and distinctive facial features. The association of pathogenic variants in PPM1D with cyclic vomiting bears not only medical attention but also further pathogenic and mechanistic evaluation. 01 juli 2023

Neurodevelopmental disorders (NDDs) often result from highly penetrant variation in one of many genes, including genes not yet characterized. Using the MatchMaker Exchange, we assembled a cohort of 22 individuals with rare, protein-altering variation in the X-linked transcriptional coregulator gene ZMYM3. Most (n=19) individuals were males; 15 males had maternally-inherited alleles, three of the variants in males arose de novo, and one had unknown inheritance. Overlapping features included developmental delay, intellectual disability, behavioral abnormalities, and a specific facial gestalt in a subset of males. Variants in almost all individuals (n=21) are missense, two of which are recurrent. Three unrelated males were identified with inherited variation at R441, a site at which variation has been previously reported in NDD-affected males, and two individuals have de novo variation at R1294. All variants affect evolutionarily conserved sites, and most are predicted to damage protein structure or function. ZMYM3 is relatively intolerant to variation in the general population, is highly expressed in the brain, and encodes a component of the KDM1A-RCOR1 chromatin-modifying complex. ChIP-seq experiments on one mutant, ZMYM3R1274W, indicate dramatically reduced genomic occupancy, supporting a hypomorphic effect. While we are unable to perform statistical evaluations to support a conclusive causative role for variation in ZMYM3 in disease, the totality of the evidence, including the presence of recurrent variation, overlapping phenotypic features, protein-modeling data, evolutionary constraint, and experimentally-confirmed functional effects, strongly supports ZMYM3 as a novel NDD gene.

SWI/SNF-related intellectual disability disorders (SSRIDDs) are rare neurodevelopmental disorders characterized by developmental disability, coarse facial features, and fifth digit/nail hypoplasia that are caused by pathogenic variants in genes that encode for members of the SWI/SNF (or BAF) family of chromatin remodeling complexes. We have identified 12 individuals with rare variants (10 loss-of-function, 2 missense) in the BICRA (BRD4 interacting chromatin remodeling complex-associated protein) gene, also known as GLTSCR1, which encodes a subunit of the non-canonical BAF (ncBAF) complex. These individuals exhibited neurodevelopmental phenotypes that include developmental delay, intellectual disability, autism spectrum disorder, and behavioral abnormalities as well as dysmorphic features. Notably, the majority of individuals lack the fifth digit/nail hypoplasia phenotype, a hallmark of most SSRIDDs. To confirm the role of BICRA in the development of these phenotypes, we performed functional characterization of the zebrafish and Drosophila orthologs of BICRA. In zebrafish, a mutation of bicra that mimics one of the loss-of-function variants leads to craniofacial defects possibly akin to the dysmorphic facial features seen in individuals harboring putatively pathogenic BICRA variants. We further show that Bicra physically binds to other non-canonical ncBAF complex members, including the BRD9/7 ortholog, CG7154, and is the defining member of the ncBAF complex in flies. Like other SWI/SNF complex members, loss of Bicra function in flies acts as a dominant enhancer of position effect variegation but in a more context-specific manner. We conclude that haploinsufficiency of BICRA leads to a unique SSRIDD in humans whose phenotypes overlap with those previously reported.

Most reported patients carrying GNAO1 mutations showed a severe phenotype characterized by early-onset epileptic encephalopathy and/or chorea.The aim was to characterize the clinical and genetic features of patients with mild GNAO1-related phenotype with prominent movement disorders.We included patients diagnosed with GNAO1-related movement disorders of delayed onset (2 years). Patients experiencing either severe or profound intellectual disability or early-onset epileptic encephalopathy were excluded.Twenty-four patients and 1 asymptomatic subject were included. All patients showed dystonia as prominent movement disorder. Dystonia was focal in 1, segmental in 6, multifocal in 4, and generalized in 13. Six patients showed adolescence or adulthood-onset dystonia. Seven patients presented with parkinsonism and 3 with myoclonus. Dysarthria was observed in 19 patients. Mild and moderate ID were present in 10 and 2 patients, respectively.We highlighted a mild GNAO1-related phenotype, including adolescent-onset dystonia, broadening the clinical spectrum of this condition. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Inborn errors of metabolism (IEM) involving the non-oxidative pentose phosphate pathway (PPP) include the two relatively rare conditions, transketolase deficiency and transaldolase deficiency, both of which can be difficult to diagnosis given their non-specific clinical presentations. Current biochemical testing approaches require an index of suspicion to consider targeted urine polyol testing. To determine whether a broad-spectrum biochemical test could accurately identify a specific metabolic pattern defining IEMs of the non-oxidative PPP, we employed the use of clinical metabolomic profiling as an unbiased novel approach to diagnosis. Subjects with molecularly confirmed IEMs of the PPP were included in this study. Targeted quantitative analysis of polyols in urine and plasma samples was accomplished with chromatography and mass spectrometry. Semi-quantitative unbiased metabolomic analysis of urine and plasma samples was achieved by assessing small molecules via liquid chromatography and high-resolution mass spectrometry. Results from untargeted and targeted analyses were then compared and analyzed for diagnostic acuity. Two siblings with transketolase (TKT) deficiency and three unrelated individuals with transaldolase (TALDO) deficiency were identified for inclusion in the study. For both IEMs, targeted polyol testing and untargeted metabolomic testing on urine and/or plasma samples identified typical perturbations of the respective disorder. Additionally, untargeted metabolomic testing revealed elevations in other PPP metabolites not typically measured with targeted polyol testing, including ribonate, ribose, and erythronate for TKT deficiency and ribonate, erythronate, and sedoheptulose 7-phosphate in TALDO deficiency. Non-PPP alternations were also noted involving tryptophan, purine, and pyrimidine metabolism for both TKT and TALDO deficient patients. Targeted polyol testing and untargeted metabolomic testing methods were both able to identify specific biochemical patterns indicative of TKT and TALDO deficiency in both plasma and urine samples. In addition, untargeted metabolomics was able to identify novel biomarkers, thereby expanding the current knowledge of both conditions and providing further insight into potential underlying pathophysiological mechanisms. Furthermore, untargeted metabolomic testing offers the advantage of having a single effective biochemical screening test for identification of rare IEMs, like TKT and TALDO deficiencies, that may otherwise go undiagnosed due to their generally non-specific clinical presentations.

Loss-of-function variants in

The nuclear factor I (NFI) family of transcription factors play an important role in normal development of multiple organs. Three NFI family members are highly expressed in the brain, and deletions or sequence variants in two of these, NFIA and NFIX, have been associated with intellectual disability (ID) and brain malformations. NFIB, however, has not previously been implicated in human disease. Here, we present a cohort of 18 individuals with mild ID and behavioral issues who are haploinsufficient for NFIB. Ten individuals harbored overlapping microdeletions of the chromosomal 9p23-p22.2 region, ranging in size from 225 kb to 4.3 Mb. Five additional subjects had point sequence variations creating a premature termination codon, and three subjects harbored single-nucleotide variations resulting in an inactive protein as determined using an in vitro reporter assay. All individuals presented with additional variable neurodevelopmental phenotypes, including muscular hypotonia, motor and speech delay, attention deficit disorder, autism spectrum disorder, and behavioral abnormalities. While structural brain anomalies, including dysgenesis of corpus callosum, were variable, individuals most frequently presented with macrocephaly. To determine whether macrocephaly could be a functional consequence of NFIB disruption, we analyzed a cortex-specific Nfib conditional knockout mouse model, which is postnatally viable. Utilizing magnetic resonance imaging and histology, we demonstrate that Nfib conditional knockout mice have enlargement of the cerebral cortex but preservation of overall brain structure and interhemispheric connectivity. Based on our findings, we propose that haploinsufficiency of NFIB causes ID with macrocephaly. ispartof: AMERICAN JOURNAL OF HUMAN GENETICS vol:103 issue:5 pages:752-768 ispartof: location:United States status: published

Points essentiels Devant un tableau d’otite externe trainante malgre un traitement bien conduit, en particulier sur un terrain immunodeprime, il faut toujours rechercher une osteomyelite de la base du crâne qui necessite un traitement antibiotique parenteral urgent de plusieurs semaines. L’otite moyenne aigue (OMA) est la plus frequente des infections bacteriennes de l’enfant. Chez l’enfant de moins de 2 ans presentant une OMA purulente, l’antibiotherapie par amoxicilline est systematique pour une duree de 8–10 jours. Apres 2 ans d’âge et si les symptomes d’OMA sont peu bruyants, un traitement symptomatique peut se justifier en premiere intention. L’otite seromuqueuse (OSM) est frequente apres un episode d’OMA et ne devient chronique qu’apres 3 mois d’evolution. La pose d’aerateurs trans-tympaniques reduit la frequence des episodes d’OMA. Toute OMA compliquee d’une meningite impose une surveillance par audiogramme et IRM de l’oreille.

Intellectual disability (ID) affects about 3% of the population and has a male gender bias. Of at least 700 genes currently linked to ID, more than 100 have been identified on the X chromosome, including KIAA2022. KIAA2022 is located on Xq13.3 and is expressed in the developing brain. The protein product of KIAA2022, X‐linked Intellectual Disability Protein Related to Neurite Extension (XPN), is developmentally regulated and is involved in neuronal migration and cell adhesion. The clinical manifestations of loss‐of‐function KIAA2022 mutations have been described previously in 15 males, born from unaffected carrier mothers, but few females. Using whole‐exome sequencing, we identified a cohort of five unrelated female patients with de novo probably gene damaging variants in KIAA2022 and core phenotypic features of ID, developmental delay, epilepsy refractory to treatment, and impaired language, of similar severity as reported for male counterparts. This study supports KIAA2022 as a novel cause of X‐linked dominant ID, and broadens the phenotype for KIAA2022 mutations.

One of the goals of evaluating a patient in the genetics clinic is to find the diagnosis that would explain his or her clinical presentation. Sometimes the patient's diagnosis remains undefined or does not explain all of the clinical findings. As clinicians are often guided by a "single disorder" paradigm, diagnosing multiple genetic conditions in the same patient requires a heightened sense of awareness. Over the last few years, we evaluated several patients (n = 14) who were found to have more than one genetic diagnosis. In this paper, we will describe their natural history and diagnoses, and draw on the lessons learned from this phenomenon, which we expect to grow in this era of next-generation diagnostic technologies. To our knowledge, this is by far the largest series of patients with double diagnoses. Based on our findings, we strongly recommend that physicians question every diagnosis to determine whether it indeed explains all of the patients' symptoms, and consider whether they should continue the diagnostic evaluation to look for a more accurate and complete set of diagnoses. © 2016 Wiley Periodicals, Inc.

Highly conserved TREX-mediated mRNA export is emerging as a key pathway in neuronal development and differentiation. TREX subunit variants cause neurodevelopmental disorders (NDDs) by interfering with mRNA export from the cell nucleus to the cytoplasm. Previously we implicated four missense variants in the X-linked THOC2 gene in intellectual disability (ID). We now report an additional six affected individuals from five unrelated families with two de novo and three maternally inherited pathogenic or likely pathogenic variants in THOC2 extending the genotypic and phenotypic spectrum. These comprise three rare missense THOC2 variants that affect evolutionarily conserved amino acid residues and reduce protein stability and two with canonical splice-site THOC2 variants that result in C-terminally truncated THOC2 proteins. We present detailed clinical assessment and functional studies on a de novo variant in a female with an epileptic encephalopathy and discuss an additional four families with rare variants in THOC2 with supportive evidence for pathogenicity. Severe neurocognitive features, including movement and seizure disorders, were observed in this cohort. Taken together our data show that even subtle alterations to the canonical molecular pathways such as mRNA export, otherwise essential for cellular life, can be compatible with life, but lead to NDDs in humans. Refereed/Peer-reviewed

Children with disabilities (CWD) are victims of abuse more frequently than children in the general population. The features of their underlying conditions make it more difficult to detect abuse and on occasion can be mistaken for abuse. Thus, the expertise of the clinical geneticist is often vital to properly identifying maltreatment in this vulnerable population. The purpose of this article is to review the magnitude of abuse in the population of CWD, to identify the aggravating factors, and to suggest practice changes in order to both diagnose and reduce the likelihood of abuse in CWD.

In front of external otitis in spite of a well-conducted treatment, especially in immunodeficient patient, it is always necessary to look for an osteomyelitis of the skull base that requires an urgent parenteral antibiotic treatment of several weeks. Acute otitis media (AOM) is the most common bacterial infection of the child. In children under 2 years with purulent AOM, antibiotic therapy with amoxicilline is systematic for a period of 8-10 days. After 2 years of age and with mild symptoms of AOM, symptomatic treatment may be justified as first-line treatment. Chronic otitis media is frequent after an episode of AOM and becomes chronic only after 3 months of evolution. Grommets reduce the frequency of AOM episodes. All AOM complicated with meningitis requires monitoring by audiogram and MRI of the ear.

Context: Heterozygous mutations in the aggrecan gene (ACAN) cause autosomal dominant short stature with accelerated skeletal maturation. Objective: We sought to characterize the phenotypic spectrum and response to growth-promoting therapies. Patients and Methods: One hundred three individuals (57 females, 46 males) from 20 families with autosomal dominant short stature and heterozygous ACAN mutations were identified and confirmed using whole-exome sequencing, targeted next-generation sequencing, and/or Sanger sequencing. Clinical information was collected from the medical records. Results: Identified ACAN variants showed perfect cosegregation with phenotype. Adult individuals had mildly disproportionate short stature [median height, −2.8 standard deviation score (SDS); range, −5.9 to −0.9] and a history of early growth cessation. The condition was frequently associated with early-onset osteoarthritis (12 families) and intervertebral disc disease (9 families). No apparent genotype–phenotype correlation was found between the type of ACAN mutation and the presence of joint complaints. Childhood height was less affected (median height, −2.0 SDS; range, −4.2 to −0.6). Most children with ACAN mutations had advanced bone age (bone age − chronologic age; median, +1.3 years; range, +0.0 to +3.7 years). Nineteen individuals had received growth hormone therapy with some evidence of increased growth velocity. Conclusions: Heterozygous ACAN mutations result in a phenotypic spectrum ranging from mild and proportionate short stature to a mild skeletal dysplasia with disproportionate short stature and brachydactyly. Many affected individuals developed early-onset osteoarthritis and degenerative disc disease, suggesting dysfunction of the articular cartilage and intervertebral disc cartilage. Additional studies are needed to determine the optimal treatment strategy for these patients.

To analyze the difference between the endolymphatic sac tumors (ELSTs) in sporadic cases and in von Hippel-Lindau (VHL) disease.Retrospective case review in a tertiary referral center.Fourteen cases of ELST, occurring since 1998, were reviewed. We analyzed the initial symptoms, characteristics of the tumor, treatment, sequelae, and follow-up for each group.The ELSTs were sporadic in 6 cases and associated with VHL disease in 8 cases. The mean age at the time of the first surgery was 26 years (range, 12-41). All except two of the patients presented with a unilateral tumor. The initial symptoms were hearing loss (n = 9), tinnitus (n = 7), and/or vertigo (n = 5). Hearing loss was more prevalent in the sporadic cases. Preoperative arteriography was performed for 4 patients, with embolization performed for 1 patient. The size of the tumor was significantly larger in the sporadic cases (31.7 mm) than in the cases of VHL disease (19.3 mm). The surgical approach was more extensive in the sporadic cases. The surgeons found 2 types of tumors. Cystic tumors with massive bleeding invading the surrounding structures (the dura mater or jugular bulb) were more common in the sporadic cases. Fibrous tumors that infiltrate the bone and have moderate bleeding were more common in the cases associated with VHL disease.Two patients with small lesions were not operated on but were followed for 6 years without tumor growth. They died of metastasis from gastric and kidney cancer. Four recurrences occurred during the 14 years of follow-up. Four facial palsies and 8 cases of profound deafness were encountered postoperatively.Sporadic tumors are more aggressive than those associated with VHL disease. Complete surgical resection should be the goal of treatment. Preoperative angiography with embolization is recommended. In some cases, embolization may be impossible, and preoperative or postoperative radiotherapy should be discussed.

International audience; Early-onset epileptic encephalopathy (EOEE) represents a heterogeneous group of severe disorders characterized by seizures, interictal epileptiform activity with a disorganized electroencephalography background, developmental regression or retardation, and onset before 1 year of age. Among a cohort of 57 individuals with epileptic encephalopathy, we ascertained two unrelated affected individuals with EOEE associated with developmental impairment and autosomal-recessive variants in AP3B2 by means of whole-exome sequencing. The targeted sequencing of AP3B2 in 86 unrelated individuals with EOEE led to the identification of an additional family. We gathered five additional families with eight affected individuals through the Matchmaker Exchange initiative by matching autosomal- recessive mutations in AP3B2. Reverse phenotyping of 12 affected individuals from eight families revealed a homogeneous EOEE phenotype characterized by severe developmental delay, poor visual contact with optic atrophy, and postnatal microcephaly. No spasticity, albinism, or hematological symptoms were reported. AP3B2 encodes the neuron-specific subunit of the AP-3 complex. Autosomal-recessive variations of AP3B1, the ubiquitous isoform, cause Hermansky-Pudlak syndrome type 2. The only isoform for the delta subunit of the AP-3 complex is encoded by AP3D1. Autosomal-recessive mutations in AP3D1 cause a severe disorder cumulating the symptoms of the AP3B1 and AP3B2 defects.

We identified five unrelated individuals with significant global developmental delay and intellectual disability (ID), dysmorphic facial features and frequent microcephaly, and de novo predicted loss-of-function variants in chromosome alignment maintaining phosphoprotein 1 (CHAMP1). Our findings are consistent with recently reported de novo mutations in CHAMP1 in five other individuals with similar features. CHAMP1 is a zinc finger protein involved in kinetochore–microtubule attachment and is required for regulating the proper alignment of chromosomes during metaphase in mitosis. Mutations in CHAMP1 may affect cell division and hence brain development and function, resulting in developmental delay and ID.

Cardiovascular abnormalities, especially structural congenital heart defects, commonly occur in malformation syndromes and genetic disorders. Individuals with syndromes comprise a significant proportion of those affected with selected congenital heart defects such as complete atrioventricular canal, interrupted arch type B, supravalvar aortic stenosis, and pulmonary stenosis. As these individuals age, they contribute to the growing population of adults with special health care needs. Although most will require longterm cardiology follow-up, primary care providers, geneticists, and other specialists should be aware of (1) the type and frequency of cardiovascular abnormalities, (2) the range of clinical outcomes, and (3) guidelines for prospective management and treatment of potential complications. This article reviews fundamental genetic, cardiac, medical, and reproductive issues associated with common genetic syndromes that are frequently associated with a cardiovascular abnormality. New data are also provided about the cardiac status of adults with a 22q11.2 deletion and with Down syndrome.

Stickler syndrome is an autosomal dominant multisystem disease. The four most affected systems are craniofacial, skeletal, ocular, and auditory. The manifestations of Stickler syndrome vary considerably among affected individuals. Audiologists and speech-language pathologists should be familiar with the characteristics associated with Stickler syndrome to facilitate early identification and appropriate management.

Contains fulltext : 88561.pdf (Publisher’s version ) (Closed access) BACKGROUND: Chromosome 17p13.3 contains extensive repetitive sequences and is a recognised region of genomic instability. Haploinsufficiency of PAFAH1B1 (encoding LIS1) causes either isolated lissencephaly sequence or Miller-Dieker syndrome, depending on the size of the deletion. More recently, both microdeletions and microduplications mapping to the Miller-Dieker syndrome telomeric critical region have been identified and associated with distinct but overlapping phenotypes. METHODS: Genome-wide microarray screening was performed on 7678 patients referred with unexplained learning difficulties and/or autism, with or without other congenital abnormalities. Eight and five unrelated individuals, respectively, were identified with microdeletions and microduplications in 17p13.3. RESULTS: Comparisons with six previously reported microdeletion cases identified a 258 kb critical region, encompassing six genes including CRK (encoding Crk) and YWHAE (encoding 14-3-3epsilon). Clinical features included growth retardation, facial dysmorphism and developmental delay. Notably, one individual with only subtle facial features and an interstitial deletion involving CRK but not YWHAE suggested that a genomic region spanning 109 kb, encompassing two genes (TUSC5 and YWHAE), is responsible for the main facial dysmorphism phenotype. Only the microduplication phenotype included autism. The microduplication minimal region of overlap for the new and previously reported cases spans 72 kb encompassing a single gene, YWHAE. These genomic rearrangements were not associated with low-copy repeats and are probably due to diverse molecular mechanisms. CONCLUSIONS: The authors further characterise the 17p13.3 microdeletion and microduplication phenotypic spectrum and describe a smaller critical genomic region allowing identification of candidate genes for the distinctive facial dysmorphism (microdeletions) and autism (microduplications) manifestations. 01 mei 2010

The phakomatoses of particular interest to neurologists including Sturge-Weber syndrome, neurofibromatosis type 1, neurofibromatosis type 2, Bannayan-Riley-Ruvalcaba syndrome, and Proteus syndrome are presented. The physical manifestations required for clinical diagnosis, the neurologic features, and recommendations for management are given. The molecular etiology and genetic aspects of these disorders are briefly discussed as well as future implications of on-going research.

To study the incidence, location, pre- and postoperative symptoms (hearing loss, tinnitus, vertigo, facial palsy), preoperative diagnostic imaging, and surgical treatment of labyrinthine fistulae (LF).Retrospective case review.Twenty-two cases of LF over 382 mastoid operations performed in a 168-month period.Clinical, imaging, and surgical correlation of extensive fistulae and bone fistulae.LF prevalence was 5.8%. The main primary symptoms were otorrhea and hypoacusis. Only four patients presented vertigo as their main complaint. All patients underwent preoperative computed tomographic (CT) scans and preoperative audiometry. LF diagnosis was made before surgery for 100% of patients on the basis of CT scan. A second fistula was, however, misdiagnosed by imaging in two patients. With respect to surgical technique, a canal wall down procedure was performed in 77% and a conservative procedure was performed in 23%. Fistula was located in the horizontal semicircular canal in 100% of cases, and in 9%, a second fistula was operatively diagnosed. In 91% of cases, the matrix was removed, whereas it was left in the course of a canal down procedure in 9%. With a follow-up of 5.7 years, hearing remained unchanged in 80% of patients.Surgery with removal of the cholesteatoma matrix and sealing of the fistula with temporalis fascia is a safe procedure that can help preserve cochlear function. The choice of a canal down procedure would be influenced by cholesteatoma characteristics rather than by the finding of an LF.

Objective To study the incidence, location, pre- and postoperative symptoms (hearing loss, tinnitus, vertigo, facial palsy), preoperative diagnostic imaging, and surgical treatment of labyrinthine fistulae (LF). Design Retrospective case review. Patients Twenty-two cases of LF over 382 mastoid operations performed in a 168-month period. Main outcome measures Clinical, imaging, and surgical correlation of extensive fistulae and bone fistulae. Results LF prevalence was 5.8%. The main primary symptoms were otorrhea and hypoacusis. Only four patients presented vertigo as their main complaint. All patients underwent preoperative computed tomographic (CT) scans and preoperative audiometry. LF diagnosis was made before surgery for 100% of patients on the basis of CT scan. A second fistula was, however, misdiagnosed by imaging in two patients. With respect to surgical technique, a canal wall down procedure was performed in 77% and a conservative procedure was performed in 23%. Fistula was located in the horizontal semicircular canal in 100% of cases, and in 9%, a second fistula was operatively diagnosed. In 91% of cases, the matrix was removed, whereas it was left in the course of a canal down procedure in 9%. With a follow-up of 5.7 years, hearing remained unchanged in 80% of patients. Conclusions Surgery with removal of the cholesteatoma matrix and sealing of the fistula with temporalis fascia is a safe procedure that can help preserve cochlear function. The choice of a canal down procedure would be influenced by cholesteatoma characteristics rather than by the finding of an LF.

La dissection sur os temporal (OT) cadavérique est actuellement considérée comme la référence pour la formation des internes en chirurgie otologique. L'accès aux laboratoires d’anatomie et la disponibilité des OT cadavériques peuvent être difficiles. L'objectif de cette étude prospective était d'évaluer l'intérêt de la simulation en réalité virtuelle pour l’apprentissage de la mastoïdectomie chez des internes d’Oto-Rhino- Laryngologie (ORL) novices.Matériel et MéthodesVingt internes d’ORL en troisième semestre, provenant de six villes d’internat différentes, étaient répartis en deux groupes. Les dix internes du groupe « sans simulation » ont réalisé directement une mastoïdectomie sur OT cadavérique, tandis que les dix internes du groupe « simulation » ont bénéficié de deux séances d’entrainement sur le simulateur en réalité virtuelle Voxel-Man Tempo® avant de réaliser la mastoïdectomie sur cadavre. La performance et la technique de dissection ont été évaluées sur OT cadavérique par deux évaluateurs à l’aide d’échelles d’évaluation validées, respectivement Welling Scale et Task-Based Checklist.RésultatsLes deux groupes étaient comparables concernant l’expérience et les connaissances anatomiques en chirurgie otologique. L’évaluation de la performance lors de la dissection sur OT cadavérique mettait en évidence une supériorité significative pour le groupe « simulation » (p = 0.02) avec un score moyen de performance de 14.3 [10-17] sur 20, comparativement à 11.4 [7-15] pour le groupe « sans simulation ». L’évaluation de la technique montrait également une supériorité significative pour le groupe « simulation » (p = 0.002) avec un score moyen de technique de 16.7 [14-19] sur 21, comparativement à 13.1 [9-16] pour le groupe « sans simulation ».ConclusionL’entrainement sur simulateur en réalité virtuelle semblait améliorer la performance et les compétences techniques pour la réalisation d’une mastoïdectomie sur cadavre chez des internes d’ORL novices. L’apprentissage de la chirurgie par simulation en réalité virtuelle peut donc être envisagé pour optimiser la formation des internes, et pour pallier au manque de disponibilité des OT cadavériques.

En France, le développement de la chirurgie ambulatoire est aujourd'hui favorisé par des incitations financières, avec pour objectif d'atteindre 66,2% d'activité ambulatoire à l'horizon 2020.Une étude rétrospective de l'activité ambulatoire au sein du service d'ORL de l'hôpital de Bicêtre de 2000 à 2014 et une étude prospective de l'activité de programmation chirurgicale de mars à décembre 2016 a permis d'analyser l' évolution des pratiques chirurgicales dont le potentiel d' activité transférable dans l'unité de chirurgie ambulatoire (UCA) et les problèmes organisationnels liés à cette pratique.4715 actes ont été programmés entre 2000 et 2014 à l'UCA, avec un taux d'ambulatoire de 30,8% en 2014, 13,1% d'actes annulés entre J-5 et J0, et un taux de repli moyen faible de 1,8%. Les actes rhinologiques et otologiques, surtout développés en ambulatoire à partie de 2009, représentent respectivement 16,7% et 8,8% de l'activité ambulatoire en 2014.147 actes pratiqués au bloc commun pouvaient être réalisés en UCA, soit 15,5% de l'activité globale. Les deux principales raisons de cette pratique sont un délai d'accès trop long à l'UCA et un matériel chirurgical inadapté à l'UCA.En cas de transfert complet, le taux de pratique ambulatoire passerait de 64,2% à 65,7% pour les actes amygdalectomie, adénoïdectomie et pose/dépose d'aérateurs trans-tympaniques de 38,8% à 50,7% pour les actes rhinologiques et de 10,0% à 46,6 % pour les actes otologiques.Au vu des règles tarifaires incitatives actuelles et de la tarification ambulatoire attendue à la baisse, il est important de réaliser aujourd'hui les investissements nécessaires au développement de l'activité chirurgicale ambulatoire.