44 results on '"Rutter MM"'
Search Results
2. Growth Hormone Improves Growth in Duchenne Muscular Dystrophy Boys with Steroid-Induced Growth Failure.
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Rutter, MM, primary, Collins, J, additional, Woo, JG, additional, Rose, SR, additional, Sawnani, H, additional, Cripe, LH, additional, Kinnett, KJ, additional, Hor, K, additional, and Wong, BL, additional
- Published
- 2010
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3. Long-term endocrine sequelae of childhood cancer.
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Rutter MM and Rose SR
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- 2007
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4. Defining Success in the Delivery of Fertility-Related Care for Patients with Differences of Sex Development.
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Streich-Tilles T, Morrison A, Schafer-Kalkhoff T, Gardner M, Suorsa-Johnson KI, Baskin A, Weidler EM, van Leeuwen K, Sandberg DE, and Rutter MM
- Abstract
Introduction: Individuals with differences of sex development (DSD) experience complex, often competing, medical and psychosocial challenges surrounding fertility. The study aimed to characterize how "success" in fertility-related care is conceptualized and attained among individuals with a DSD, their parents or caregivers, healthcare providers, and other stakeholders., Methods: As part of a larger study, DSD stakeholders (n = 110) participated in semi-structured interviews covering the clinical care of patients with DSD. Primary questions included: "What is a successful outcome in DSD care?" and "How do you achieve it?" with fertility as either a spontaneous or suggested topic of discussion. Transcripts were analyzed utilizing a phenomenological approach. This analysis focuses on the extracted themes related to fertility., Results: Fertility was discussed by 19/24 individuals with DSD, 12/19 parents or caregivers, 35/37 healthcare providers, and 19/30 other stakeholders. Components of successful fertility-related care included: 1) specific discussions surrounding the relationship between DSD and fertility potential, options for fertility preservation, and options for non-biologic parenthood; 2) early and repeated introduction of these topics; and 3) consideration of age, developmental maturity, and cultural context on decisions around fertility. Challenges include the lack of fertility outcome data in this population and the irreversibility of gonadectomy. Trade-offs identified included anatomic typicality versus function, fertility preservation versus cancer risk reduction, and balancing the different priorities of stakeholders., Discussion/conclusions: A wide range of DSD stakeholders highlighted the importance of addressing fertility concerns in achieving favorable outcomes for individuals with DSD. These stakeholder perspectives should inform fertility-related education, shared decision-making processes, and clinical care., (S. Karger AG, Basel.)
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- 2024
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5. Preferences in Clinical Care of Individuals With Differences of Sex Development.
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Avanceña ALV, Rose AM, Gardner MD, Rutter MM, Schafer-Kalkhoff T, Suorsa-Johnson KI, van Leeuwen KD, Weidler EM, Gebremariam A, Sandberg DE, and Prosser LA
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- Humans, Female, Male, Child, Adolescent, Patient Satisfaction, Adult, Patient Care Team, Child, Preschool, Disorders of Sex Development therapy, Disorders of Sex Development psychology, Patient Preference
- Abstract
Objectives: To identify the most important attributes related to the process of achieving, and outcomes associated with, successful care for differences of sex development (DSD)., Methods: We developed a best-worst scaling survey administered to 520 DSD stakeholders, including individuals or family members of those with DSD, health care specialists, and patient support and advocacy representatives. Fourteen process-related attributes and 16 outcome-related attributes were identified through qualitative research. We estimated relative importance scores and coefficients from regression analysis to understand the relative importance of attributes and conducted latent class analysis to explore heterogeneity in preferences., Results: The 3 most important process attributes were (1) good communication between care team and patient/family, (2) care team educated patient/family about condition, and (3) care team incorporates the values of patient/family. The 3 most important outcome attributes were (1) patient satisfaction, (2) patient mental health, and (3) treatment maintains physical health. Latent class analyses showed that respondents had heterogeneous preferences. For process-related attributes, we identified 3 respondent groups: "Patient autonomy and support" (46% of respondents), "Education and care transitions" (18%), and "Shared decision-making" (36%). For outcome-related attributes, we identified 2 respondent groups: "Preserving function and appearance" (59% of respondents) and "Patient health and satisfaction" (41%)., Conclusions: Outcomes such as patient satisfaction and health were the most important outcome attributes, and good communication and education from the care team were the most important process attributes. Respondents expressed heterogeneous preferences for selected DSD care attributes that providers should consider to improve satisfaction with and quality of DSD care.
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- 2024
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6. Appendicular lean mass index changes in patients with Duchenne muscular dystrophy and Becker muscular dystrophy.
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Wong BL, Summer S, Horn PS, Rutter MM, Rybalsky I, Tian C, Shellenbarger KC, and Kalkwarf HJ
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- Male, Adolescent, Humans, Child, Mutation, Genotype, Phenotype, Biomarkers, Muscular Dystrophy, Duchenne complications, Muscular Dystrophy, Duchenne genetics
- Abstract
Introduction: Mutations in the 79 exons of the dystrophin gene result in muscle wasting and weakness of varying clinical severity, ranging from severe/typical Duchenne muscular dystrophy (DMD) to intermediate DMD and mild Becker muscular dystrophy (BMD), depending on the frameshift of the mutation. We previously reported that males with DMD have progressively declining appendicular lean mass (ALM) and ALM index (ALMI) with age and worsening functional motor ability compared with healthy controls. These indices have not been studied in patients with intermediate DMD and BMD phenotypes and across DMD genotypes. In this study, we compared age-related trajectories of ALM and ALMI of patients who had (1) BMD without functional mobility deficits with patients who had DMD at different stages of disease and healthy controls; (2) a DMD intermediate phenotype with patients who had a typical DMD phenotype; and (3) DMD categorized by genotype., Methods: We conducted a retrospective review of ALM and ALMI data from 499 patients (ages 5-23 years) with DMD (466 typical and 33 intermediate) and 46 patients (ages 5-21 years) with BMD (without functional mobility deficits and functional mobility score of 1). Patients were grouped according to age reflecting disease stage (ages 5 to <7, 7 to <10, 10 to <14, and 14 to <20 years) and genotype (mutations in exons 1-30, 31-44, 45-62, and 63-79)., Results: ALM and ALMI trajectories of patients with BMD paralleled those of healthy controls until adolescence, in contrast to patients with DMD. ALMI Z-scores of patients with BMD remained within ±2 SD without decline while those of patients with DMD fell below -2 SD around age 12 years. Patients with BMD had increasing ALM and ALMI with age, with peak accrual between ages 10 to <14 years. ALMI declined after age 14 years for those with intermediate DMD compared with 10 years for patients with typical DMD. Patients with mutations in exons 63-79 had a greater decline in ALMI as compared with those with other genotypes after age 10 years., Conclusions: Age-related changes in ALMI in patients with BMD and intermediate DMD differ from those with typical DMD, reflecting their clinical phenotypes. ALM and ALMI should be further studied in patients with BMD and DMD subtypes for their potential value as surrogate markers to characterize the severity of BMD and DMD and inform clinical care decisions and clinical trial designs., (© 2023 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)
- Published
- 2023
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7. "It became easier once I knew": Stakeholder perspectives for educating children and teenagers about their difference of sex development.
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Weidler EM, Suorsa-Johnson KI, Baskin AS, Fagerlin A, Gardner MD, Rutter MM, Schafer-Kalkhoff T, van Leeuwen K, and Sandberg DE
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- Adult, Humans, Child, Adolescent, Educational Status, Shame, Sexual Development, Parents psychology, Health Personnel psychology
- Abstract
Objective: Secrecy about a child's difference of sex development (DSD) can lead to internalized shame and stigma. We explored how teenagers and adults with DSD, parents, healthcare providers, and allied professionals value and perceive patient education., Methods: Stakeholders (n = 110) completed qualitative semi-structured interviews. Relevant themes for educational content were queried and organized., Results: Education was consistently identified as essential to successful outcomes. There was less consistency in how to educate patients. Disagreement existed regarding who should champion the education process. Participants believed medically relevant information should be shared gradually with attention to developmental capacity. Details were lacking regarding how much or what information to share. Participants noted that vetted resources were helpful. Benefits of sharing condition-specific information with patients included supporting their psychosocial development. Barriers included parental resistance to sharing information due to shame/stigma, and cultural and/or family dynamics., Conclusions: Stakeholders' different perspectives regarding patient DSD education warrant future research to focus on the design, evaluation, and implementation of education-focused interventions., Practice Implications: Healthcare providers are responsible for supporting the education of children and teenagers with DSD about their condition. When considering barriers, adopting a cultural or family systems framework can reduce parental resistance and promote open dialogue., Competing Interests: Conflict of interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)
- Published
- 2023
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8. Successful Treatment of Hypoglycemia With Alpelisib in Pediatric Patients With PIK3CA -Related Overgrowth Spectrum.
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Nasomyont N, Rutter MM, and Backeljauw PF
- Abstract
Activating mutations in the PIK3CA gene, causing phosphoinositide 3-kinase (PI3K) hyperactivation, are rare causes of hypoglycemia. We report the novel use of alpelisib (a PI3K inhibitor) for the treatment of hypoketotic, hypoinsulinemic hypoglycemia in 2 children with PIK3CA -related overgrowth spectrum (PROS). Patient 1 was a 7-month-old girl who presented with a hypoglycemic seizure. Despite nutritional management including continuous feeds, she continued to have frequent hypoglycemia. At age 2.8 years, alpelisib was started at 50 mg daily and titrated to 100 mg daily. She was weaned off nocturnal continuous feeds by 8 months. She developed colitis when the alpelisib dose was increased to 125 mg, but this resolved with a dose decrease and medical management. At age 5.3 years, she was doing well with rare hypoglycemia. Her accelerated growth stabilized. Patient 2 was a 3-year-old boy who developed hypoglycemia in early infancy. Alpelisib 50 mg daily was started due to recurrent hypoglycemia despite nutritional management. He came off continuous feeds after 4 months, with decreased hypoglycemia frequency. At age 4.5 years, he had not experienced side effects from treatment. In conclusion, alpelisib appears to be effective in decreasing PROS-related hypoglycemia frequency and severity and should be considered for refractory hypoglycemia in this condition., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)
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- 2023
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9. Surgical Decision-Making for Individuals with Differences of Sex Development: Stakeholders' views.
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Weidler EM, Gardner M, Suorsa-Johnson KI, Schafer-Kalkhoff T, Rutter MM, Sandberg DE, and van Leeuwen K
- Abstract
Introduction: Advocacy and human rights organizations have called for a moratorium on elective surgical procedures until the patient is able to fully participate in the decision-making process. Due to the controversial nature surrounding surgery in differences of sex development (DSD) care, we aimed to assess the factors that teens and adults with DSD, parents, healthcare providers and other allied professionals consider pertinent to complex surgical decisions in DSD., Methods: Stakeholders (n=110) in DSD care participated in semi-structured interviews exploring features and potential determinants of successful healthcare outcomes. Audio-recordings were transcribed, coded, and analyzed using qualitative data software. Codes for "Process of Decision-Making" and "Successful Outcome-Surgery/Appearance/Function" were further searched using keywords "surgery," "procedure," and "timing.", Results: Several themes were identified: 1) The nature or type of the decision being made; 2) Who should be involved in the decision-making process; 3) Timing of conversations about surgery; 4) Barriers to decision-making surrounding surgery; 5) The elements of surgical decision-making; and 6) The optimal approach to surgical decision-making. Many stakeholders believed children and adolescents with DSD should be involved in the process as developmentally appropriate., Conclusion: DSD include a wide range of diagnoses, some of which may require urogenital reconstruction to relieve obstruction, achieve continence, and/or address other anatomical differences whether cosmetic or functional. Adolescents and adults with DSD desired autonomy and to be part of the decision-making process. Parents were divided in their opinion of who should be involved in making elective surgical decisions: the child or parents as proxy medical decision-makers. Providers and other professionals stressed the importance of process and education around surgical decisions. Ongoing research examines how decision-makers evaluate tradeoffs associated with decision options., Competing Interests: Conflict of Interest Erica M. Weidler is the paid Executive Director of Accord Alliance. No other conflicts to disclose.
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- 2023
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10. Defining successful outcomes and preferences for clinical management in differences/disorders of sex development: Protocol overview and a qualitative phenomenological study of stakeholders' perspectives.
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Suorsa-Johnson KI, Gardner MD, Baskin A, Gruppen LD, Rose A, Rutter MM, Schafer-Kalkhoff T, Stacey D, van Leeuwen KD, Weidler EM, and Sandberg DE
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- Humans, Parents psychology, Qualitative Research, Sexual Development, Disorders of Sex Development diagnosis, Disorders of Sex Development psychology, Disorders of Sex Development therapy
- Abstract
Introduction: Utilizing a qualitative phenomenological design, the Defining Successful Outcomes and Trade-offs study examined stakeholder perspectives regarding optimal healthcare delivery and outcomes for individuals with a difference/disorder of sex development (DSD)., Objective: We describe study methods and provide an overview of themes and subthemes., Study Design: Interviews were conducted with individuals with a DSD (n = 24), parents of those with a DSD (n = 19), healthcare providers (n = 37), and others (n = 30). Primary questions regarding clinical management of patients with DSD were: "What is a successful outcome?" and "How do you achieve it?", Results: Themes included: understanding of DSD diagnosis and self-efficacy in management is necessary but complex; patient and family psychological well-being; support from others versus being stigmatized; affected person experiences physical health and accepts the implications of their condition; complexities in DSD decision making, roles and expectations; and knowledgeable providers and multidisciplinary teams are essential, notwithstanding persisting barriers. Participants recognized competing values potentially forcing trade-offs in decision making., Discussion: Recognition of diverse and sometimes conflicting perspectives regarding optimal pathways of care and outcomes - both within and among those with DSD and their providers -promises to enhance shared decision making., Conclusion: Diverse perspectives and perceptions of trade-offs associated with DSD healthcare emphasize the need to tailor care for patients and families., Competing Interests: Conflicts of interest None to declare., (Copyright © 2021 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)
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- 2022
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11. Creation of an Electronic Resource Repository for Differences of Sex Development (DSD): Collaboration Between Advocates and Clinicians in the DSD-Translational Research Network.
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Rutter MM, Muscarella M, Green J, Indig G, von Klan A, Kennedy K, Weidler EM, Barrett M, and Sandberg DE
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- Humans, Sexual Development, Surveys and Questionnaires, Translational Research, Biomedical, Disorders of Sex Development psychology
- Abstract
Introduction: People with differences of sex development (DSD) and their families need education about these conditions while receiving emotional and peer support to participate in shared decision-making, reduce social isolation, and optimize physical and psychosocial outcomes. Barriers to education and support include limited knowledge and awareness by healthcare providers, tension among patient and medical communities, varied quality of educational resources, and the sensitive nature of DSD. We aimed to create an electronic repository of vetted quality online resources about DSD., Methods: The electronic resource repository (e-RR) was a collaboration between affected individuals and advocates and healthcare providers in the DSD-Translational Research Network (DSD-TRN), an NIH-supported consortium of US teams committed to standardizing and optimizing care in DSD. The e-RR development and ongoing growth involved: (1) identification of resources by the project team (3 advocates and 1 physician), (2) evaluation and feedback by DSD-TRN clinical teams, (3) creation of the e-RR, and (4) review and revision. Twitter-like descriptions accompanied each entry; resources were categorized by target age, audience, and condition., Results: Thirty-seven web-based educational, peer and advocacy support, and clinician-oriented resources were reviewed. Eight of 10 DSD-TRN teams responded to a survey regarding resource inclusion. Awareness of individual resources varied widely. Consensus was achieved when opinions differed; 30 resources were included. The e-RR is available online and as a downloadable booklet at http://www.accordalliance.org/resource-guide/., Conclusion: The e-RR increases awareness of and access to vetted educational and support resources for those with DSD and healthcare providers. It represents important collaboration between advocates and providers., (© 2022 S. Karger AG, Basel.)
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- 2022
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12. The effect of oral bisphosphonate therapy on vertebral morphometry and fractures in patients with Duchenne muscular dystrophy and glucocorticoid-induced osteoporosis.
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Nasomyont N, Tian C, Hornung L, Khoury J, Hochwalt PM, Tilden JC, Wong BL, and Rutter MM
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- Bone Density, Child, Diphosphonates pharmacology, Glucocorticoids adverse effects, Humans, Thoracic Vertebrae diagnostic imaging, Muscular Dystrophy, Duchenne complications, Muscular Dystrophy, Duchenne diagnostic imaging, Muscular Dystrophy, Duchenne drug therapy, Osteoporosis chemically induced, Osteoporosis diagnostic imaging, Osteoporosis drug therapy
- Abstract
Introduction/aims: Glucocorticoid-induced osteoporosis with vertebral fractures is frequent in patients with Duchenne muscular dystrophy (DMD). In this study, we evaluated the effects of oral bisphosphonate (BP) therapy on the prevalence and severity of vertebral fractures by vertebral morphometry assessment., Methods: We reviewed the records and radiographs of patients with DMD who had been treated with oral BP (weekly alendronate) and had undergone routine spine radiographic monitoring for glucocorticoid-induced osteoporosis at Cincinnati Children's Hospital Medical Center between 2010 and 2017. Study outcomes were thoracic and lumbar vertebral fracture prevalence and severity, assessed by Genant semiquantitative grading of vertebral morphometry, for up to 5 years of treatment., Results: Fifty-two patients (median age, 11.8 years; 88% prepubertal; 31% nonambulatory) had been treated with long-term glucocorticoids (median duration, 4.7 years at BP start). Most patients (75%) had mild vertebral height loss or fractures (Genant grade = 0 or 1) at baseline. The prevalence of vertebral fractures at each year of treatment was not statistically different from that at baseline (P = .08-1.00). Serial radiographs showed no longitudinal change in severity by Genant grade in most vertebrae (64%-80%). Improvement in vertebral fracture grade was observed in some patients., Discussion: We observed stable prevalence of vertebral fractures and no change in severity by Genant grade in most vertebrae for up to 5 years of treatment. Oral BP may mitigate development or progression of vertebral fractures and be beneficial for secondary prevention of glucocorticoid-induced osteoporosis in this population., (© 2021 Wiley Periodicals LLC.)
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- 2021
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13. Emergency Planning as Part of Healthcare Transition Preparation for Patients with Duchenne Muscular Dystrophy.
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Chouteau WA, Burrows C, Wittekind SG, Rutter MM, Bange JE, Sabla GE, Rybalsky I, and Tian C
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- Caregivers, Child, Humans, Surveys and Questionnaires, Emergency Medical Services, Muscular Dystrophy, Duchenne therapy, Transition to Adult Care
- Abstract
Background: Emergency care planning is an important component of healthcare transition, particularly for patients with medical complexity. Duchenne muscular dystrophy (DMD) is a complex, progressive pediatric-onset disease affecting multiple organ systems including impairment of cardiac and pulmonary function, high risk for fractures, fat embolism, adrenal crisis and malignant hyperthermia. Appropriate interdisciplinary emergency management is critical for survival for these patients. The purpose of this quality improvement project was to develop a process to reliably share an individualized emergency care plan (ECP) with patients and their families as part of a larger plan to develop an integrated transition program., Methods: An interdisciplinary team of nurses and clinicians used the principles of quality improvement to develop a reliable process to assure patients with DMD received an individualized, multidisciplinary ECP at routine interdisciplinary clinic visits. Additionally, the project used surveys to assess patient and family satisfaction with the letter and whether it improved their knowledge of emergency care., Results: Sixty-two patients were seen during the study timeframe. All received an ECP. Sixty-two surveys were sent and twenty-three surveys were returned. Of those that responded, the majority stated the ECP increased their knowledge of emergency care., Conclusion: ECPs can be developed and disseminated to patients with DMD and their caregivers. This tool can potentially promote timely and appropriate emergency care for these patients with unique and complex medical needs., Competing Interests: Declaration of competing interest All authors have no potential conflicts of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2021
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14. The Effect of Adiposity on Cardiovascular Function and Myocardial Fibrosis in Patients With Duchenne Muscular Dystrophy.
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Henson SE, Lang SM, Khoury PR, Tian C, Rutter MM, Urbina EM, Ryan TD, Taylor MD, and Alsaied T
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- Adiposity, Contrast Media, Fibrosis, Gadolinium, Humans, Magnetic Resonance Imaging, Cine, Myocardium pathology, Retrospective Studies, Stroke Volume, Ventricular Function, Left, Cardiomyopathies diagnostic imaging, Cardiomyopathies epidemiology, Cardiomyopathies etiology, Heart Diseases diagnostic imaging, Heart Diseases epidemiology, Heart Diseases etiology, Muscular Dystrophy, Duchenne complications, Muscular Dystrophy, Duchenne diagnostic imaging, Muscular Dystrophy, Duchenne pathology
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Background Patients with Duchenne muscular dystrophy (DMD) develop cardiomyopathy because of a dystrophin deficiency causing fibrofatty replacement of the myocardium. Corticosteroid use and mobility limitations place these patients at risk for increased adiposity. We sought to determine the association of adiposity with cardiovascular dysfunction in patients with DMD. Methods and Results This was a retrospective review of patients with DMD who underwent both cardiac magnetic resonance imaging and dual-energy x-ray absorptiometry within 1 year. The cardiac magnetic resonance imaging parameters included left ventricular ejection fraction and the presence of late gadolinium enhancement (LGE positive [LGE+]). The adiposity indices, measured by dual-energy x-ray absorptiometry, included percentage of body fat, whole body fat mass indexed to height, and body mass index. A total of 324 patients were identified. Fifty-two percent had LGE+, and 36% had cardiac dysfunction (left ventricular ejection fraction <55%). Patients with cardiac dysfunction had higher whole body fat mass indexed to height and body mass index on univariate analysis (mean difference between patients with and without cardiac dysfunction: +2.9 kg/m, P =0.001; and +1.5 kg/m
2 , P =0.03, respectively). whole body fat mass indexed to height remained independently associated with cardiac dysfunction on multivariable analysis after adjusting for age, LGE+, and corticosteroid duration. High whole body fat mass indexed to height and percentage of body fat were associated with LGE+ on univariate analysis (mean difference between patients with and without LGE+: +2.0 kg/m, P =0.02; and +2.4%, P =0.02, respectively). Using multivariable analysis, including age and cardiac dysfunction, high percentage of body fat remained independently associated with LGE+. Conclusions This study demonstrates an independent association of adiposity with cardiac dysfunction and LGE+ in patients with DMD. Preventing adiposity may mitigate the later development of ventricular dysfunction in DMD.- Published
- 2021
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15. Age-related changes in appendicular lean mass in males with Duchenne muscular dystrophy: A retrospective review.
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Summer SS, Wong BL, Rutter MM, Horn PS, Tian C, Rybalsky I, Shellenbarger KC, and Kalkwarf HJ
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- Absorptiometry, Photon, Adolescent, Age Factors, Case-Control Studies, Child, Child, Preschool, Disease Progression, Functional Status, Glucocorticoids therapeutic use, Humans, Linear Models, Male, Mobility Limitation, Muscle, Skeletal pathology, Muscular Dystrophy, Duchenne drug therapy, Muscular Dystrophy, Duchenne pathology, Muscular Dystrophy, Duchenne physiopathology, Organ Size, Retrospective Studies, Young Adult, Body Composition, Extremities diagnostic imaging, Muscle, Skeletal diagnostic imaging, Muscular Dystrophy, Duchenne diagnostic imaging
- Abstract
Background: Appendicular lean mass (ALM) trajectory in males with Duchenne muscular dystrophy (DMD) has potential applicability for treatment and research and has not been characterized., Methods: This chart review included longitudinal data on 499 males with DMD receiving glucocorticoids and 693 controls, ages 5 to 22.9 y. ALM (kg) was measured by dual energy x-ray absorptiometry (DXA). Appendicular lean mass index (ALMI, kg/m
2 ) was calculated for height adjustment. Reference centiles were generated using data from healthy controls, and ALM and ALMI Z-scores were calculated for patients with DMD. Generalized linear models were used to estimate median Z-scores by age and functional mobility status (FMS) score. ALM velocity by age was modeled using superimposition, translation and rotation (SITAR)., Results: Compared to controls, males with DMD had lower ALM from an early age. ALMI Z-scores dropped below 0 at age 8 y or FMS of 2, and below -2.0 at age 13 y or FMS of 3 (P < .05). Age at peak ALM velocity was similar in both groups, but the magnitude was higher in controls (3.5 vs. 0.7 kg/y, P < .0001). Patients with DMD had a transient loss of ALM around age 12 y, an increase at age 14 y, then a further decline at age 16 y, remaining low thereafter., Conclusions: Males with DMD have progressive decline in lean mass with age and worsening functional mobility. DXA measurement of ALM may be useful for monitoring lean mass status in patients with DMD, providing valuable information for individual treatment plans and research endeavors., (© 2020 Wiley Periodicals LLC.)- Published
- 2021
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16. Safety and efficacy of teriparatide treatment for severe osteoporosis in patients with Duchenne muscular dystrophy.
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Nasomyont N, Keefe C, Tian C, Hornung L, Khoury J, Tilden JC, Hochwalt P, Jackson E, Rybalsky I, Wong BL, and Rutter MM
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- Adolescent, Adult, Bone Density, Humans, Teriparatide therapeutic use, Young Adult, Bone Density Conservation Agents adverse effects, Muscular Dystrophy, Duchenne complications, Muscular Dystrophy, Duchenne drug therapy, Osteoporosis drug therapy
- Abstract
Osteoporosis is a major concern in patients with Duchenne muscular dystrophy. In this novel study of teriparatide treatment in 6 patients with severe osteoporosis, bone health (fractures, vertebral morphometry, and DXA) remained stable, with no adverse events. These findings will help inform future osteoporosis research in this challenging population., Introduction: Despite standard therapy with vitamin D and bisphosphonates (BP), many patients with Duchenne muscular dystrophy (DMD) continue to sustain fragility fractures due to long-term glucocorticoid treatment and limited mobility. We aimed to evaluate the safety and efficacy of teriparatide for the treatment of severe osteoporosis in adolescent and young adult patients with DMD., Methods: We prospectively treated 6 patients with DMD who had severe osteoporosis with teriparatide 20 mcg subcutaneously daily for 1-2 years. Inclusion criteria were long-term glucocorticoid therapy, and severe osteoporosis despite treatment with BP, or intolerance to BP. We examined long bone and vertebral fracture outcomes, including vertebral morphometry measures, bone mineral density and content, bone formation markers, safety indices, and adverse events., Results: The mean age at teriparatide start was 17.9 years (range 13.9-22.1 years). All 6 patients were on daily glucocorticoids (mean ± SD; duration 10.9 ± 2.5 years) and 5 were non-ambulatory. Five patients had been treated with BP for 7.9 ± 4.2 years. All had vertebral and a history of long bone fragility fractures at baseline. Vertebral heights and Genant fracture grading remained stable. Long bone fracture rate appeared to decrease (from 0.84/year to 0.09/year); one patient sustained a long bone fracture at 6 months of treatment. Trajectories for change in bone mineral density and content were not different post- vs. pre-teriparatide. Procollagen type 1 amino-terminal propeptide (P1NP) increased, while laboratory safety indices remained stable and non-concerning. No adverse events were observed., Conclusion: In six patients with DMD treated with teriparatide for severe osteoporosis, we observed stable bone health and modest increases in P1NP, without safety concerns. Further studies are needed to better understand teriparatide efficacy for treatment of osteoporosis in patients with DMD.
- Published
- 2020
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17. XY Gonadal Dysgenesis in a Phenotypic Female Identified by Direct-to-Consumer Genetic Testing.
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Kim A, Abell K, Johnson J, Cizek S, Breech L, Ernst MM, Hopkin RJ, Kennedy K, Stanek J, Strine AC, and Rutter MM
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- Adolescent, Biomarkers, Tumor blood, Dysgerminoma blood, Dysgerminoma diagnostic imaging, Dysgerminoma genetics, Female, Gender Identity, Genes, sry genetics, Gonadal Dysgenesis, 46,XY blood, Gonadoblastoma blood, Gonadoblastoma diagnostic imaging, Gonadoblastoma genetics, Humans, Lung Neoplasms diagnostic imaging, Lung Neoplasms secondary, Ovarian Neoplasms diagnostic imaging, Phenotype, Direct-to-Consumer Advertising, Dysgerminoma secondary, Genetic Testing methods, Gonadal Dysgenesis, 46,XY diagnosis, Gonadoblastoma secondary, Ovarian Neoplasms pathology
- Abstract
We report a 16-year-old phenotypic female with 46,XY complete gonadal dysgenesis and metastatic dysgerminoma, unexpectedly discovered through direct-to-consumer (DTC) commercial genetic testing. This case underscores the importance of timely interdisciplinary care, including psychosocial intervention and consideration of gonadectomy, to optimize outcomes for individuals with differences of sex development. Her unique presentation highlights the implications of DTC genetic testing in a new diagnostic era and informs general pediatricians as well as specialists of nongenetic services about the value, capabilities, and limitations of DTC testing., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2020 by the American Academy of Pediatrics.)
- Published
- 2020
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18. Oral bisphosphonate treatment in patients with Duchenne muscular dystrophy on long term glucocorticoid therapy.
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Tian C, Wong BL, Hornung L, Khoury JC, Rybalsky I, Shellenbarger KC, and Rutter MM
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- Absorptiometry, Photon, Adolescent, Alendronate therapeutic use, Bone Density, Child, Child, Preschool, Humans, Lumbar Vertebrae diagnostic imaging, Male, Osteoporosis complications, Osteoporosis drug therapy, Retrospective Studies, Bone Density Conservation Agents therapeutic use, Diphosphonates therapeutic use, Glucocorticoids adverse effects, Muscular Dystrophy, Duchenne complications
- Abstract
Osteoporosis is a major problem in patients with Duchenne muscular dystrophy (DMD), due to glucocorticoid therapy and muscle weakness. Evidence on which to base optimal prevention and treatment strategies, including bisphosphonate use, in DMD are limited. Our objective was to describe bone health outcomes of oral alendronate treatment in patients with DMD and glucocorticoid-induced osteoporosis. We retrospectively studied 54 patients treated between 2005 and 2017, and assessed changes in dual-energy x-ray absorptiometry (DXA) whole body and lumbar spine bone mineral density and content, and lateral distal femur bone mineral density. We also examined vertebral fracture development in a subset with serial spine radiographs. Pre-alendronate DXA Z-score trajectories decreased progressively. Over three years post-alendronate initiation, Z-score trajectories improved (p<0.01) at most sites compared with pre-alendronate trajectories. Height-adjusted Z-score trajectories for lumbar spine bone mineral density (p = 0.01) and whole body bone mineral content (p = 0.0004) also improved. The positive trajectories did not seem to be sustained long term in those treated up to 6 years. Radiographic vertebral findings in 43 patients appeared stable. In conclusion, oral bisphosphonate therapy using alendronate was associated with improvement of DXA bone health indices during the first three years of treatment, and may help mitigate progression of osteoporosis in glucocorticoid-treated patients with DMD., (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Published
- 2020
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19. Poorly differentiated thyroid carcinoma of childhood and adolescence: a distinct entity characterized by DICER1 mutations.
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Chernock RD, Rivera B, Borrelli N, Hill DA, Fahiminiya S, Shah T, Chong AS, Aqil B, Mehrad M, Giordano TJ, Sheridan R, Rutter MM, Dehner LP, Foulkes WD, and Nikiforov YE
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- Adolescent, Female, Humans, Male, Mutation, Young Adult, Adenocarcinoma genetics, Adenocarcinoma pathology, DEAD-box RNA Helicases genetics, Ribonuclease III genetics, Thyroid Neoplasms genetics, Thyroid Neoplasms pathology
- Abstract
Poorly differentiated thyroid carcinomas (PDTC) in young individuals are rare and their clinical and histopathologic features, genetic mechanisms, and outcomes remain largely unknown. Here, we report a detailed characterization of a series of six PDTC in patients ≤21 years old defined by Turin diagnostic criteria studied for mutations and gene fusions characteristic of thyroid cancer using targeted next-generation sequencing (NGS) and whole-exome sequencing (WES). All tumors had solid, insular, or trabecular growth pattern and high mitotic rate, and five out of six tumors showed tumor necrosis. Targeted NGS assay identified somatic mutations in the DICER1 gene in five of six (83%) tumors, all of which were "hotspot" mutations encoding the metal-ion binding sites of the RNase IIIb domain of DICER1. WES was performed in five cases which confirmed all hotspot mutations and detected two tumors with additional inactivating DICER1 alterations. Of these two, one was a germline pathogenic DICER1 variant and the other had loss of heterozygosity for DICER1. No other mutations or gene fusions characteristic of adult well-differentiated thyroid cancer and PDTC (BRAF, RAS, TERT, RET/PTC, and other) were detected. On follow-up, available for five patients, three patients died of disease 8-24 months after diagnosis, whereas two were alive with no disease. The results of our study demonstrate that childhood- and adolescent-onset PDTC are genetically distinct from adult-onset PDTC in that they are strongly associated with DICER1 mutations and may herald DICER1 syndrome in a minority. As such, all young persons with PDTC may benefit from genetic counseling. Furthermore, their clinically aggressive behavior contrasts sharply with the indolent nature of the great majority of thyroid tumors with DICER1 mutations reported to date.
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- 2020
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20. Newborn Screening Protocols and Positive Predictive Value for Congenital Adrenal Hyperplasia Vary across the United States.
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Speiser PW, Chawla R, Chen M, Diaz-Thomas A, Finlayson C, Rutter MM, Sandberg DE, Shimy K, Talib R, Cerise J, Vilain E, and Délot EC
- Abstract
Newborn screening for congenital adrenal hyperplasia (CAH) caused by 21-hydroxylase deficiency is mandated throughout the US. Filter paper blood specimens are assayed for 17-hydroxyprogesterone (17OHP). Prematurity, low birth weight, or critical illness cause falsely elevated results. The purpose of this report is to highlight differences in protocols among US state laboratories. We circulated a survey to state laboratory directors requesting qualitative and quantitative information about individual screening programs. Qualitative and quantitative information provided by 17 state programs were available for analysis. Disease prevalence ranged from 1:9941 to 1:28,661 live births. Four state laboratories mandated a second screen regardless of the initial screening results; most others did so for infants in intensive care units. All but one program utilized birthweight cut-points, but cutoffs varied widely: 17OHP values of 25 to 75 ng/mL for birthweights >2250-2500 g. The positive predictive values for normal birthweight infants varied from 0.7% to 50%, with the highest predictive values based in two of the states with a mandatory second screen. Data were unavailable for negative predictive values. These data imply differences in sensitivity and specificity in CAH screening in the US. Standardization of newborn screening protocols could improve the positive predictive value., Competing Interests: Conflicts of Interest: The authors declare no conflict of interest.
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- 2020
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21. Recombinant human insulin-like growth factor-1 therapy for 6 months improves growth but not motor function in boys with Duchenne muscular dystrophy.
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Rutter MM, Wong BL, Collins JJ, Sawnani H, Taylor MD, Horn PS, and Backeljauw PF
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- Absorptiometry, Photon, Blood Glucose metabolism, Blood Glucose Self-Monitoring, Body Composition, Child, Drug Therapy, Combination, Glucocorticoids therapeutic use, Humans, Magnetic Resonance Imaging, Male, Muscular Dystrophy, Duchenne metabolism, Muscular Dystrophy, Duchenne physiopathology, Quality of Life, Treatment Outcome, Walk Test, Body Height, Growth Substances therapeutic use, Insulin Resistance, Insulin-Like Growth Factor I therapeutic use, Muscle Strength, Muscular Dystrophy, Duchenne drug therapy, Recombinant Proteins therapeutic use
- Abstract
Introduction: Recombinant human insulin-like growth factor-1 (rhIGF-1) is a growth factor and has anabolic effects on muscle. We investigated whether rhIGF-1 therapy: 1) improves or preserves muscle function; and 2) improves growth in boys with Duchenne muscular dystrophy (DMD)., Methods: In this study we compared prepubescent, ambulatory, glucocorticoid-treated boys with DMD (n = 17) vs controls (glucocorticoid therapy only, n = 21) in a 6-month-long, prospective, randomized, controlled trial of subcutaneous rhIGF-1 therapy. The primary outcome was 6-minute walk distance (6MWD). Secondary outcomes included height velocity (HV), change in height standard deviation score (ΔHtSDS), motor function, cardiopulmonary function, body composition, insulin sensitivity, quality of life, and safety., Results: Change in 6MWD was similar between groups (rhIGF-1 vs controls [mean ± SD]: 3.4 ± 32.4 vs -5.1 ± 50.2 meters, P = .53). Treated subjects grew more than controls (HV: 6.5 ± 1.7 vs 3.3 ± 1.3 cm/year, P < .0001; 6-month ΔHtSDS: 0.25, P < .0001). Lean mass and insulin sensitivity increased in treated subjects., Discussion: In boys with DMD, 6 months of rhIGF-1 therapy did not change motor function, but it improved linear growth., (© 2020 Wiley Periodicals, Inc.)
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- 2020
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22. Loss-of-Function Variants in PPP1R12A: From Isolated Sex Reversal to Holoprosencephaly Spectrum and Urogenital Malformations.
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Hughes JJ, Alkhunaizi E, Kruszka P, Pyle LC, Grange DK, Berger SI, Payne KK, Masser-Frye D, Hu T, Christie MR, Clegg NJ, Everson JL, Martinez AF, Walsh LE, Bedoukian E, Jones MC, Harris CJ, Riedhammer KM, Choukair D, Fechner PY, Rutter MM, Hufnagel SB, Roifman M, Kletter GB, Delot E, Vilain E, Lipinski RJ, Vezina CM, Muenke M, and Chitayat D
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- Abnormalities, Multiple genetics, Adolescent, Child, Child, Preschool, Disorders of Sex Development genetics, Female, Gestational Age, Holoprosencephaly genetics, Humans, Male, Phenotype, Pregnancy, Urogenital Abnormalities genetics, Abnormalities, Multiple pathology, Disorders of Sex Development pathology, Holoprosencephaly pathology, Mutation, Myosin-Light-Chain Phosphatase genetics, Urogenital Abnormalities pathology
- Abstract
In two independent ongoing next-generation sequencing projects for individuals with holoprosencephaly and individuals with disorders of sex development, and through international research collaboration, we identified twelve individuals with de novo loss-of-function (LoF) variants in protein phosphatase 1, regulatory subunit 12a (PPP1R12A), an important developmental gene involved in cell migration, adhesion, and morphogenesis. This gene has not been previously reported in association with human disease, and it has intolerance to LoF as illustrated by a very low observed-to-expected ratio of LoF variants in gnomAD. Of the twelve individuals, midline brain malformations were found in five, urogenital anomalies in nine, and a combination of both phenotypes in two. Other congenital anomalies identified included omphalocele, jejunal, and ileal atresia with aberrant mesenteric blood supply, and syndactyly. Six individuals had stop gain variants, five had a deletion or duplication resulting in a frameshift, and one had a canonical splice acceptor site loss. Murine and human in situ hybridization and immunostaining revealed PPP1R12A expression in the prosencephalic neural folds and protein localization in the lower urinary tract at critical periods for forebrain division and urogenital development. Based on these clinical and molecular findings, we propose the association of PPP1R12A pathogenic variants with a congenital malformations syndrome affecting the embryogenesis of the brain and genitourinary systems and including disorders of sex development., (Published by Elsevier Inc.)
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- 2020
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23. Differentiated Thyroid Cancer in the Pediatric/Adolescent Population: Evolution of Treatment.
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Remiker AS, Chuang J, Corathers S, Rutter MM, Rutter MJ, Myer CM 4th, Gelfand MJ, Trout AT, and Geller JI
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- Adolescent, Child, Child, Preschool, Female, Humans, Iodine Radioisotopes therapeutic use, Male, Retrospective Studies, Thyroid Neoplasms genetics, Thyroid Neoplasms pathology, Thyroidectomy, Treatment Outcome, Young Adult, Antineoplastic Agents therapeutic use, Thyroid Neoplasms therapy
- Abstract
Differentiated thyroid cancer (DTC) is the most common cancer in adolescents and young adults. In 2015, the American Thyroid Association published guidelines for management of pediatric DTC. We report our institutional experience and highlight changing practices and new opportunities. A retrospective analysis of all patients diagnosed with DTC from 2001 to 2016 was performed. Among 59 eligible patients, 31 (53%), 15 (25%), and 13 (22%) had low-risk, intermediate-risk, and high-risk disease, respectively. Half (15/31) of low-risk and all intermediate-risk/high-risk patients received radioactive iodine (I-131) ablation. For low-risk patients, average I-131 dose decreased from 80 to 42.05 mCi, and the percentage of patients who received I-131 decreased over time. Eleven of 16 patients with tumor genomic data were found to have somatic targetable (n=6) or germline (n=5) mutations. Persistent/recurrent disease was only present in high-risk (n=8) and intermediate-risk (n=1) patients. Two patients with iodine-refractory disease received trametinib to enhance radioiodine uptake. All patients were alive at follow-up (median, 5 y; range, 1 to 15 y). Coincident with the recent American Thyroid Association guidelines, the use of I-131 in low-risk patients has decreased over time in our practice. Tumor sequencing and cancer genetic evaluation may help redefine opportunities for treatment of high-risk patients and family counseling.
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- 2019
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24. Central Diabetes Insipidus in a Patient With NFKB2 Mutation: Expanding the Endocrine Phenotype in DAVID Syndrome.
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Nasomyont N, Lindsley AW, Assa'ad A, Dawson DB, Neilson DE, Brady CC, and Rutter MM
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Context: Deficient anterior pituitary with variable immune deficiency (DAVID) syndrome is a recently described, rare disorder characterized by anterior pituitary hormone deficiencies and common variable immunodeficiency associated with NFKB2 mutations. Posterior pituitary hormone deficiencies have not been reported in patients with DAVID syndrome., Case Description: We report a pediatric patient who initially presented with hypogammaglobulinemia and alopecia totalis, who was identified to have a de novo NFKB2 mutation at one year of age. He developed central diabetes insipidus and central adrenal insufficiency at three and four years of age, respectively. At seven years of age, he had not developed GH or TSH deficiencies. Whole exome sequencing ruled out known genetic causes of central diabetes insipidus, adrenal insufficiency, and hypopituitarism., Conclusion: This is a report of central diabetes insipidus in a patient with DAVID syndrome caused by an NFKB2 mutation. This case report expands the evolving endocrine phenotype associated with NFKB2 mutations beyond anterior pituitary deficiencies., (Copyright © 2019 Endocrine Society.)
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- 2019
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25. Comparison of Pulmonary Function Decline in Steroid-Treated and Steroid-Naïve Patients with Duchenne Muscular Dystrophy.
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Sawnani H, Horn PS, Wong B, Darmahkasih A, Rybalsky I, Shellenbarger KC, Tian C, Rutter MM, Simakajornboon N, Amin R, Gurbani N, Pascoe J, Burrows C, Khirani S, Amaddeo A, and Fauroux B
- Subjects
- Adolescent, Child, Disease Progression, Glucocorticoids therapeutic use, Humans, Male, Muscular Dystrophy, Duchenne physiopathology, Prednisone therapeutic use, Pregnenediones therapeutic use, Retrospective Studies, Muscular Dystrophy, Duchenne drug therapy, Respiratory Function Tests
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Objective: To describe and compare the lung function decline in patients with Duchenne muscular dystrophy on glucocorticoid therapy in contrast with glucocorticoid-naïve patients, and to define the deciles of pulmonary decline in glucocorticoid-treated patients., Study Design: This retrospective study examined lung function of patients with Duchenne muscular dystrophy over 6 years of age followed between 2001 and 2015 at 2 centers-glucocorticoid-treated patients in Cincinnati, Ohio, and glucocorticoid-naïve patients in Paris, France. Forced vital capacity (FVC, FVC%), forced expiratory volume in 1 second, maximal inspiratory pressure, maximal expiratory pressure, and peak expiratory flow data were analyzed. Only FVC data were available for the French cohort., Results: There were 170 glucocorticoid-treated patients (92%), 5 patients (2.7%) with past glucocorticoid use, and 50 French glucocorticoid-naïve patients. The peak absolute FVC was higher and was achieved at earlier ages in glucocorticoid-treated compared with glucocorticoid-naïve patients (peak FVC, 2.4 ± 0.6 L vs 1.9 ± 0.7 L; P < .0001; ages 13.5 ± 3.0 years vs 14.3 ± 2.8 years; P = .03). The peak FVC% was also higher and was achieved at earlier ages in glucocorticoid-treated patients (peak FVC%, 105.1 ± 25.1% vs 56 ± 20.9%; P < .0001; ages 11.9 ± 2.9 years vs 13.6 ± 3.2 years; P = .002). Rates of decline for both groups varied with age. Maximal rates of decline were 5.0 ± 0.26% per year (12-20 years) for glucocorticoid-treated and 5.1 ± 0.39% per year for glucocorticoid-naïve patients (11-20 years; P = .2). Deciles of FVC% decline in glucocorticoid-treated patients show that patients experience accelerated decline at variable ages., Conclusions: These data describe nonlinear rates of decline of pulmonary function in patients with Duchenne muscular dystrophy, with improved function in glucocorticoid-treated patients. FVC% deciles may be a useful tool for clinical and research use., (Copyright © 2019 Elsevier Inc. All rights reserved.)
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- 2019
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26. Homozygous Calcium-Sensing Receptor Polymorphism R544Q Presents as Hypocalcemic Hypoparathyroidism.
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Cavaco BM, Canaff L, Nolin-Lapalme A, Vieira M, Silva TN, Saramago A, Domingues R, Rutter MM, Hudon J, Gleason JL, Leite V, and Hendy GN
- Subjects
- Amino Acid Substitution, Arginine genetics, Female, Glutamic Acid genetics, Homozygote, Humans, Hypocalcemia complications, Hypoparathyroidism complications, Young Adult, Hypocalcemia genetics, Hypoparathyroidism genetics, Polymorphism, Single Nucleotide, Receptors, Calcium-Sensing genetics
- Abstract
Context: Autosomal dominant hypocalcemia type 1 (ADH1) is caused by heterozygous activating mutations in the calcium-sensing receptor gene (CASR). Whether polymorphisms that are benign in the heterozygous state pathologically alter receptor function in the homozygous state is unknown., Objective: To identify the genetic defect in an adolescent female with a history of surgery for bilateral cataracts and seizures. The patient has hypocalcemia, hyperphosphatemia, and low serum PTH level. The parents of the proband are healthy., Methods: Mutation testing of PTH, GNA11, GCM2, and CASR was done on leukocyte DNA of the proband. Functional analysis in transfected cells was conducted on the gene variant identified. Public single nucleotide polymorphism (SNP) databases were searched for the presence of the variant allele., Results: No mutations were identified in PTH, GNA11, and GCM2 in the proband. However, a germline homozygous variant (c.1631G>A; p.R544Q) in exon 6 of the CASR was identified. Both parents are heterozygous for the variant. The variant allele frequency was near 0.1% in SNP databases. By in vitro functional analysis, the variant was significantly more potent in stimulating both the Ca2+i and MAPK signaling pathways than wild type when transfected alone (P < 0.05) but not when transfected together with wild type. The overactivity of the mutant CaSR is due to loss of a critical structural cation-π interaction., Conclusions: The patient's hypoparathyroidism is due to homozygosity of a variant in the CASR that normally has weak or no phenotypic expression in heterozygosity. Although rare, this has important implications for genetic counseling and clinical management.
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- 2018
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27. Psychosocial Screening in Disorders/Differences of Sex Development: Psychometric Evaluation of the Psychosocial Assessment Tool.
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Ernst MM, Gardner M, Mara CA, Délot EC, Fechner PY, Fox M, Rutter MM, Speiser PW, Vilain E, Weidler EM, and Sandberg DE
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- Child, Disorders of Sex Development pathology, Disorders of Sex Development physiopathology, Female, Humans, Male, Psychometrics, Reproducibility of Results, Risk Assessment, Disorders of Sex Development psychology, Registries, Sexual Development
- Abstract
Background/aims: Utilization of a psychosocial screener to identify families affected by a disorder/difference of sex development (DSD) and at risk for adjustment challenges may facilitate efficient use of team resources to optimize care. The Psychosocial Assessment Tool (PAT) has been used in other pediatric conditions. The current study explored the reliability and validity of the PAT (modified for use within the DSD population; PAT-DSD)., Methods: Participants were 197 families enrolled in the DSD-Translational Research Network (DSD-TRN) who completed a PAT-DSD during a DSD clinic visit. Psychosocial data were extracted from the DSD-TRN clinical registry. Internal reliability of the PAT-DSD was tested using the Kuder-Richardson-20 coefficient. Validity was examined by exploring the correlation of the PAT-DSD with other measures of caregiver distress and child emotional-behavioral functioning., Results: One-third of families demonstrated psychosocial risk (27.9% "Targeted" and 6.1% "Clinical" level of risk). Internal reliability of the PAT-DSD Total score was high (α = 0.86); 4 of 8 subscales met acceptable internal reliability. A priori predicted relationships between the PAT-DSD and other psychosocial measures were supported. The PAT-DSD Total score related to measures of caregiver distress (r = 0.40, p < 0.001) and to both caregiver-reported and patient self-reported behavioral problems (r = 0.61, p < 0.00; r = 0.37, p < 0.05)., Conclusions: This study provides evidence for the reliability and validity of the PAT-DSD. Given variability in the internal reliability across subscales, this measure is best used to screen for overall family risk, rather than to assess specific psychosocial concerns., (© 2019 S. Karger AG, Basel.)
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- 2018
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28. Low bone mineral density and fractures are highly prevalent in pediatric patients with spinal muscular atrophy regardless of disease severity.
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Wasserman HM, Hornung LN, Stenger PJ, Rutter MM, Wong BL, Rybalsky I, Khoury JC, and Kalkwarf HJ
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- Absorptiometry, Photon, Adolescent, Child, Child, Preschool, Female, Fractures, Bone epidemiology, Humans, Infant, Male, Muscular Atrophy, Spinal complications, Muscular Atrophy, Spinal epidemiology, Osteoporosis diagnostic imaging, Osteoporosis epidemiology, Prevalence, Severity of Illness Index, Bone Density physiology, Fractures, Bone etiology, Muscular Atrophy, Spinal physiopathology, Osteoporosis etiology
- Abstract
Patients with Spinal Muscular Atrophy (SMA) are at risk for poor bone health. The prevalence of fractures, low areal bone mineral density (aBMD; Z-score ≤-2.0) of the lateral distal femur and of osteoporosis by SMA subtype is not known. We aimed to describe the natural history of bone health in patients with SMA prior to bisphosphonate treatment. We reviewed data from 85 eligible patients with SMA ages 12 months to 18 years, seen at a single institution between January 2005 and July 2016. Fracture history was reported at annual clinic visits. aBMD was obtained from dual energy x-ray absorptiometry scans of the lumbar spine, total body, and lateral distal femur. 85% of patients had aBMD Z-scores ≤-2.0 SD and were progressively lower with worsening SMA severity. Longitudinal aBMD Z-scores of the lateral distal femur decreased with age. Fractures occurred in 38% (32/85) of patients with the femur being the most common location (25 of 57 fractures). Thirteen percent of patients fulfilled criteria for osteoporosis. Low aBMD and femur fractures are highly prevalent in all SMA subtypes from a young age; however, few patients met the criteria for osteoporosis. Poor bone health may be an under-recognized comorbidity of SMA., (Copyright © 2017. Published by Elsevier B.V.)
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- 2017
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29. Long-Term Outcome of Interdisciplinary Management of Patients with Duchenne Muscular Dystrophy Receiving Daily Glucocorticoid Treatment.
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Wong BL, Rybalsky I, Shellenbarger KC, Tian C, McMahon MA, Rutter MM, Sawnani H, and Jefferies JL
- Subjects
- Adolescent, Age Factors, Child, Cohort Studies, Dose-Response Relationship, Drug, Drug Administration Schedule, Exercise Therapy methods, Follow-Up Studies, Fractures, Bone chemically induced, Fractures, Bone physiopathology, Humans, Insulin Resistance, Long-Term Care, Male, Muscular Dystrophy, Duchenne diagnosis, Muscular Dystrophy, Duchenne rehabilitation, Osteoporosis chemically induced, Osteoporosis physiopathology, Prednisone administration & dosage, Prednisone adverse effects, Pregnenediones administration & dosage, Pregnenediones adverse effects, Retrospective Studies, Risk Assessment, Severity of Illness Index, Treatment Outcome, Weight Gain, Glucocorticoids administration & dosage, Glucocorticoids adverse effects, Muscular Dystrophy, Duchenne drug therapy, Patient Care Team organization & administration
- Abstract
Objective: To evaluate clinical outcomes and steroid side effects in a cohort of patients with Duchenne muscular dystrophy (DMD) treated with long-term daily glucocorticoid therapy. Although daily glucocorticoid therapy has been shown to extend ambulatory function in DMD, less frequent dosing is often used because of side effect concerns., Study Design: Retrospective study of 97 patients with DMD aged 10 to <16 years treated with daily glucocorticoid (89% on deflazacort) for a mean of 8.5 years. Outcome measures were motor, pulmonary, and cardiac function, and scoliosis. Side effects were growth failure and weight gain, facial fullness, blood pressure, bone health, cataracts, gastrointestinal symptoms, behavior, hypertrichosis, and need for medication interventions., Results: For 13- to 16-year-old patients, 40% could rise from the floor and 50% could perform the 30-foot run test. Forced vital capacity for the entire cohort was well preserved. Thirteen percent of younger (10- to <13-year-old) and 21% of older patients had findings of left ventricle systolic dysfunction. Six percent (all aged 16 years) developed scoliosis (Cobb angle >20 degrees). Eighty-six percent had normal weight velocities; 30% had no increased facial fullness; 72% had short stature; and 19% had asymptomatic cataracts. Asymptomatic spine compression deformities were noted in 76% and long bone fractures in 30%. One patient stopped glucocorticoid because of behavioral concerns., Conclusions: With evidence for improved outcomes and manageable side effects, we recommend use of daily glucocorticoid therapy for patients with DMD with anticipatory management of side effects and a coordinated interdisciplinary care approach., (Copyright © 2016 Elsevier Inc. All rights reserved.)
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- 2017
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30. Global Application of the Assessment of Communication Skills of Paediatric Endocrinology Fellows in the Management of Differences in Sex Development Using the ESPE E-Learning.Org Portal.
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Kranenburg LJC, Reerds STH, Cools M, Alderson J, Muscarella M, Magrite E, Kuiper M, Abdelgaffar S, Balsamo A, Brauner R, Chanoine JP, Deeb A, Fechner P, German A, Holterhus PM, Juul A, Mendonca BB, Neville K, Nordenstrom A, Oostdijk W, Rey RA, Rutter MM, Shah N, Luo X, Grijpink K, and Drop SLS
- Subjects
- Humans, Infant, Newborn, Truth Disclosure, Communication, Disorders of Sex Development diagnosis, Empathy, Endocrinology, Parents psychology, Professional-Family Relations
- Abstract
Background: Information sharing in chronic conditions such as disorders of/differences in sex development (DSD) is essential for a comprehensive understanding by parents and patients. We report on a qualitative analysis of communication skills of fellows undergoing training in paediatric endocrinology. Guidelines are created for the assessment of communication between health professionals and individuals with DSD and their parents., Methods: Paediatric endocrinology fellows worldwide were invited to study two interactive online cases (www.espe-elearning.org) and to describe a best practice communication with (i) the parents of a newborn with congenital adrenal hyperplasia and (ii) a young woman with 46,XY gonadal dysgenesis. The replies were analysed regarding completeness, quality, and evidence of empathy. Guidelines for structured assessment of responses were developed by 22 senior paediatric endocrinologists worldwide who assessed 10 selected replies. Consensus of assessors was established and the evaluation guidelines were created., Results: The replies of the fellows showed considerable variation in completeness, quality of wording, and evidence of empathy. Many relevant aspects of competent clinical communication were not mentioned; 15% (case 1) and 17% (case 2) of the replies were considered poor/insufficient. There was also marked variation between 17 senior experts in the application of the guidelines to assess communication skills. The guidelines were then adjusted to a 3-level assessment with empathy as a separate key item to better reflect the qualitative differences in the replies and for simplicity of use by evaluators., Conclusions: E-learning can play an important role in assessing communication skills. A practical tool is provided to assess how information is shared with patients with DSD and their families and should be refined by all stakeholders, notably interdisciplinary health professionals and patient representatives., (© 2017 S. Karger AG, Basel.)
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- 2017
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31. Bone health measures in glucocorticoid-treated ambulatory boys with Duchenne muscular dystrophy.
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Tian C, Wong BL, Hornung L, Khoury JC, Miller L, Bange J, Rybalsky I, and Rutter MM
- Subjects
- Absorptiometry, Photon, Adolescent, Bone Density, Bone and Bones diagnostic imaging, Bone and Bones drug effects, Child, Child, Preschool, Disability Evaluation, Disease Progression, Fractures, Bone complications, Fractures, Bone diagnostic imaging, Fractures, Bone physiopathology, Glucocorticoids adverse effects, Humans, Male, Muscular Dystrophy, Duchenne complications, Muscular Dystrophy, Duchenne diagnostic imaging, Neuromuscular Agents adverse effects, Osteoporosis complications, Osteoporosis diagnostic imaging, Osteoporosis physiopathology, Retrospective Studies, Walking, Bone and Bones physiopathology, Glucocorticoids therapeutic use, Muscular Dystrophy, Duchenne drug therapy, Muscular Dystrophy, Duchenne physiopathology, Neuromuscular Agents therapeutic use
- Abstract
Osteoporosis is a major problem in boys with Duchenne Muscular Dystrophy (DMD), attributable to muscle weakness and glucocorticoid therapy. Consensus regarding bone health assessment and management is lacking. Lumbar spine areal bone mineral density (defined as bone mass per area of bone) by dual-energy X-ray absorptiometry (DXA) is frequently the primary measure used, but has limitations for boys with DMD. We retrospectively studied 292 ambulant glucocorticoid-treated boys with DMD categorized by functional mobility score, FMS 1, 2 or 3. We assessed DXA whole body and lumbar spine areal bone mineral density and content Z-scores adjusted for age and height, lateral distal femur areal bone mineral density Z-scores, frequency of fractures, and osteoporosis by International Society for Clinical Densitometry 2013 criteria. Whole body and femoral DXA indices decreased, while spine fractures increased, with declining motor function. Lumbar spine areal bone mineral density Z-scores appeared to improve with declining motor function. Bone mineral content Z-scores were consistently lower than corresponding bone mineral density Z-scores. Our findings highlight the complexity of assessing bone health in boys with DMD. Bone health indices worsened with declining motor function in ambulant boys, but interpretation was affected by measure and skeletal site examined. Whole body bone mineral content may be a valuable measure in boys with DMD. Lumbar spine areal bone mineral density Z-score as an isolated measure could be misleading. Comprehensive management of osteoporosis in boys with DMD should include vertebral fracture assessment., (Copyright © 2016 Elsevier B.V. All rights reserved.)
- Published
- 2016
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32. Late endocrine effects of childhood cancer.
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Rose SR, Horne VE, Howell J, Lawson SA, Rutter MM, Trotman GE, and Corathers SD
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- Adrenocorticotropic Hormone deficiency, Adult, Bone Diseases, Metabolic etiology, Child, Cranial Irradiation adverse effects, Diabetes Insipidus etiology, Female, Growth Disorders etiology, Humans, Hyperprolactinemia etiology, Hypogonadism etiology, Hypothyroidism etiology, Infertility etiology, Male, Metabolic Syndrome etiology, Obesity etiology, Puberty, Delayed etiology, Puberty, Precocious etiology, Sexual Dysfunction, Physiological etiology, Antineoplastic Agents adverse effects, Endocrine System Diseases etiology, Neoplasms therapy, Radiotherapy adverse effects, Survivors
- Abstract
The cure rate for paediatric malignancies is increasing, and most patients who have cancer during childhood survive and enter adulthood. Surveillance for late endocrine effects after childhood cancer is required to ensure early diagnosis and treatment and to optimize physical, cognitive and psychosocial health. The degree of risk of endocrine deficiency is related to the child's sex and their age at the time the tumour is diagnosed, as well as to tumour location and characteristics and the therapies used (surgery, chemotherapy or radiation therapy). Potential endocrine problems can include growth hormone deficiency, hypothyroidism (primary or central), adrenocorticotropin deficiency, hyperprolactinaemia, precocious puberty, hypogonadism (primary or central), altered fertility and/or sexual function, low BMD, the metabolic syndrome and hypothalamic obesity. Optimal endocrine care for survivors of childhood cancer should be delivered in a multidisciplinary setting, providing continuity from acute cancer treatment to long-term follow-up of late endocrine effects throughout the lifespan. Endocrine therapies are important to improve long-term quality of life for survivors of childhood cancer.
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- 2016
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33. DICER1 Mutations and Differentiated Thyroid Carcinoma: Evidence of a Direct Association.
- Author
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Rutter MM, Jha P, Schultz KA, Sheil A, Harris AK, Bauer AJ, Field AL, Geller J, and Hill DA
- Subjects
- Adenocarcinoma genetics, Adenocarcinoma pathology, Adolescent, Carcinoma pathology, Carcinoma, Papillary, Child, Exons genetics, Female, Focal Nodular Hyperplasia genetics, Focal Nodular Hyperplasia pathology, Humans, Male, Mutation genetics, Mutation, Missense genetics, Pedigree, Thyroid Cancer, Papillary, Thyroid Neoplasms pathology, Thyroidectomy, Carcinoma genetics, DEAD-box RNA Helicases genetics, Ribonuclease III genetics, Thyroid Neoplasms genetics
- Abstract
Context: DICER1 germline mutation carriers have an increased predisposition to cancer, such as pleuropulmonary blastoma (PPB) and Sertoli-Leydig cell tumor (SLCT), and a high prevalence of multinodular goiter (MNG). Although differentiated thyroid carcinoma (DTC) has been reported in some DICER1 mutation carriers with PPB treated with chemotherapy, the association of DTC with DICER1 mutations is not well established., Case Description: We report a family with DICER1 mutation and familial DTC without a history of chemotherapy. A 12-year-old female (patient A) and her 14-year-old sister (patient B) presented with MNG. Family history was notable for a maternal history of DTC and bilateral ovarian SLCT. Both sisters underwent total thyroidectomy. Pathological examination showed nodular hyperplasia and focal papillary thyroid carcinoma within hyperplastic nodules. Subsequently, patient A developed virilization secondary to a unilateral ovarian SLCT. During her evaluation, an incidental cystic nephroma was also found. Three other siblings had MNG on surveillance ultrasound examination; two had thyroidectomies, and one had two microscopic foci of papillary carcinoma. Patient A, her mother, and four affected siblings had a germline heterozygous pathogenic DICER1 mutation c.5441C>T in exon 25, resulting in an amino acid change from p.Ser1814Leu of DICER1. Somatic DICER1 RNase IIIb missense mutations were identified in thyroid nodules from three of the four siblings., Conclusions: This family provides novel insight into an emerging phenotype for DICER1 syndrome, with evidence that germline DICER1 mutations are associated with an increased risk of developing familial DTC, even in the absence of prior treatment with chemotherapy.
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- 2016
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34. Endocrine disorders in Fanconi anemia: recommendations for screening and treatment.
- Author
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Petryk A, Kanakatti Shankar R, Giri N, Hollenberg AN, Rutter MM, Nathan B, Lodish M, Alter BP, Stratakis CA, and Rose SR
- Subjects
- Adult, Child, Endocrine System Diseases etiology, Fanconi Anemia complications, Glucose Metabolism Disorders diagnosis, Glucose Metabolism Disorders etiology, Glucose Metabolism Disorders therapy, Growth Disorders diagnosis, Growth Disorders etiology, Growth Disorders therapy, Human Growth Hormone deficiency, Human Growth Hormone therapeutic use, Humans, Malnutrition diagnosis, Malnutrition etiology, Malnutrition therapy, Mass Screening methods, Thinness diagnosis, Thinness etiology, Thinness therapy, Endocrine System Diseases diagnosis, Endocrine System Diseases therapy, Fanconi Anemia diagnosis, Fanconi Anemia therapy, Mass Screening standards, Practice Guidelines as Topic
- Abstract
Context: Endocrine problems are common in patients with Fanconi anemia (FA). About 80% of children and adults with FA have at least one endocrine abnormality, including short stature, GH deficiency, abnormal glucose or insulin metabolism, dyslipidemia, hypothyroidism, pubertal delay, hypogonadism, or impaired fertility. The goal of this report is to provide an overview of endocrine abnormalities and guidelines for routine screening and treatment to allow early diagnosis and timely intervention., Evidence Acquisition: This work is based on a comprehensive literature review, including relevant articles published between 1971 and 2014, and proceedings of a Consensus Conference held by the Fanconi Anemia Research Fund in 2013., Evidence Synthesis: The panel of experts collected published evidence and discussed its relevance to reflect current information about the endocrine care of children and adults with FA before the Consensus Conference and through subsequent deliberations that led to the consensus., Conclusions: Individuals with FA should be routinely screened for endocrine abnormalities, including evaluation of growth; glucose, insulin, and lipid metabolism; thyroid function; puberty; gonadal function; and bone mineral metabolism. Inclusion of an endocrinologist as part of the multidisciplinary patient care team is key to providing comprehensive care for patients with FA.
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- 2015
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35. Complexities of gender assignment in 17β-hydroxysteroid dehydrogenase type 3 deficiency: is there a role for early orchiectomy?
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Chuang J, Vallerie A, Breech L, Saal HM, Alam S, Crawford P, and Rutter MM
- Abstract
Background: 17β-Hydroxysteroid dehydrogenase type-3 (17βHSD-3) deficiency is a rare cause of 46,XY disorders of sex development. The enzyme converts androstenedione to testosterone, necessary for masculinization of male genitalia in utero. 17βHSD-3 deficiency is frequently diagnosed late, at puberty, following virilization, with consequent female-to-male gender reassignment in 39-64%. The decision for sex of rearing is difficult, especially if diagnosed in early childhood. Consensus guidelines are equivocal or support male gender assignment. Long-term outcomes data to guide decisions are also lacking; however, in the few cases of early diagnosis and orchiectomy, female gender retention appears more likely.We report two patients with 17βHSD-3 deficiency, who presented at unusual ages, in whom female gender was chosen. We performed a focused literature review and summary of gender outcomes in 17βHSD-3 deficiency following early orchiectomy., Cases: Patient A was a phenotypic female who presented at one year of age with bilateral inguinal hernias and external female genitalia. Testes were identified at surgery. The karyotype was 46,XY. She was initially diagnosed with complete androgen insensitivity syndrome; however, androgen receptor mutation analysis was negative. Human chorionic gonadotropin stimulation yielded a low testosterone: androstenedione ratio (0.6, normal >0.8). Genetic testing demonstrated compound heterozygosity for two known mutations of the HSD17B3 gene. She underwent bilateral orchiectomy at two years of age.Patient B was born with female genitalia and virilized at 13 years of age. She did not seek evaluation until 22 years of age. Her karyotype was 46,XY. She had bilateral inguinal testes and low testosterone: androstenedione ratio (0.3). HSD17B3 gene sequencing showed her to be a compound heterozygote for two known mutations. She identified herself as female and underwent bilateral orchiectomy and estrogen replacement therapy., Conclusions: These two patients highlight the complexities of diagnosis and management in 17βHSD-3 deficiency. Although existing data are limited, early orchiectomy is likely to result in retention of female gender identity, avoiding the complications related to virilization in adolescence. As such, it is important to pursue a definitive diagnosis to guide clinical decisions, and to have the support and long term follow up with an inter-disciplinary disorders of sex development team.
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- 2013
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36. Endocrine evaluation of children with and without Shwachman-Bodian-Diamond syndrome gene mutations and Shwachman-Diamond syndrome.
- Author
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Myers KC, Rose SR, Rutter MM, Mehta PA, Khoury JC, Cole T, and Harris RE
- Subjects
- Adolescent, Bone Marrow Diseases metabolism, Child, Child, Preschool, Dwarfism metabolism, Exocrine Pancreatic Insufficiency metabolism, Female, Humans, Infant, Lipomatosis metabolism, Male, Mutation, Phenotype, Retrospective Studies, Shwachman-Diamond Syndrome, Young Adult, Bone Marrow Diseases genetics, Dwarfism genetics, Endocrine System metabolism, Exocrine Pancreatic Insufficiency genetics, Lipomatosis genetics
- Abstract
Objective: To characterize the endocrine phenotype of patients with Shwachman-Diamond syndrome (SDS)., Study Design: Clinically indicated endocrine screening data from 43 patients with SDS or SDS-like presentation were analyzed according to sex, age, and genetic testing. In addition to 25 patients with biallelic Shwachman-Bodian-Diamond syndrome (SBDS) gene mutations, we evaluated 18 patients with cytopenias who were receiving pancreatic enzyme replacement but were without SBDS mutation. We performed a retrospective review of growth records and clinically indicated endocrine evaluations., Results: Of patients with SBDS mutations, 2 had low stimulated growth hormone levels, 2 had mildly elevated thyrotropin levels, 5 had abnormal glucose levels, and 1 had an elevated follicle-stimulating hormone level (post transplantation). In contrast, 1 patient without SBDS mutations had postprandial hyperglycemia and 3 had mildly low free thyroxine levels without short stature. Endocrine abnormalities were identified in 19% of short patients and 26% of the whole group. Of patients with SBDS mutations, 56% had a height expressed in SD units from the mean for age and sex of <-1.8, in contrast to only 12% of patients without SBDS mutations (38% of the whole group). Body mass index z score was significantly greater in the group with SBDS mutations (P<.001)., Conclusion: Although short stature was more common in patients with SBDS mutations, no consistent endocrine phenotype was observed in patients with SDS regardless of genetic testing., (Copyright © 2013 Mosby, Inc. All rights reserved.)
- Published
- 2013
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37. Growth hormone treatment in boys with Duchenne muscular dystrophy and glucocorticoid-induced growth failure.
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Rutter MM, Collins J, Rose SR, Woo JG, Sucharew H, Sawnani H, Hor KN, Cripe LH, and Wong BL
- Subjects
- Body Height drug effects, Body Weight drug effects, Child, Glucocorticoids therapeutic use, Human Growth Hormone adverse effects, Humans, Male, Muscular Dystrophy, Duchenne physiopathology, Prednisone adverse effects, Prednisone therapeutic use, Pregnenediones therapeutic use, Treatment Outcome, Glucocorticoids adverse effects, Growth Disorders chemically induced, Human Growth Hormone therapeutic use, Muscular Dystrophy, Duchenne drug therapy, Pregnenediones adverse effects
- Abstract
This study evaluated efficacy and safety of growth hormone treatment in Duchenne muscular dystrophy boys with glucocorticoid-induced growth failure. We reviewed 39 consecutive boys (average age 11.5 years; 32 ambulatory) treated with growth hormone for 1 year during a four-year period. Boys were on long-term daily deflazacort or prednisone (mean duration 5 ± 2.2 years; dosing regimen prednisone 0.75 mg/kg/day equivalent). Primary outcomes were growth velocity and height-for-age z-scores (height SD) at 1 year. Height velocity increased from 1.3 ± 0.2 to 5.2 ± 0.4 cm/year on growth hormone (p<0.0001). Pre-growth hormone decline in height SD (-0.5 ± 0.2SD/year) stabilized at height SD -2.9 ± 0.2 on growth hormone (p<0.0001). The rate of weight gain was unchanged, at 2.8 ± 0.6 kg/year pre-growth hormone and 2.6 ± 0.7 kg/year at 1 year. Motor function decline was similar pre-growth hormone and at 1 year. Cardiopulmonary function was unchanged. Three experienced side effects. In this first comprehensive report of growth hormone in Duchenne muscular dystrophy, growth hormone improved growth at 1 year, without detrimental effects observed on neuromuscular and cardiopulmonary function., (Copyright © 2012 Elsevier B.V. All rights reserved.)
- Published
- 2012
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38. Endocrine phenotype of children and adults with Fanconi anemia.
- Author
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Rose SR, Myers KC, Rutter MM, Mueller R, Khoury JC, Mehta PA, Harris RE, and Davies SM
- Subjects
- Adolescent, Adult, Body Height, Body Mass Index, Child, Child, Preschool, Fanconi Anemia blood, Fanconi Anemia therapy, Female, Glucose Intolerance complications, Hematopoietic Stem Cells, Hormones blood, Humans, Hypogonadism complications, Hypothyroidism complications, Male, Phenotype, Young Adult, Fanconi Anemia complications
- Abstract
Background: Features of Fanconi anemia (FA) are well known, including bone marrow failure, congenital anomalies such as radial anomalies, renal and ear anomalies, tracheo-esophageal fistula, imperforate anus, and elevated risk for cancer. We sought to further characterize the endocrine phenotype in children and adults with FA., Procedure: Clinically indicated endocrine evaluation data from 120 persons with FA, including 78 children (43 female) and 42 young adults (who had achieved adult height, 19 female), were entered in an institutional review board-approved database. Data were analyzed according to gender, birth weight, FA complementation group, and whether or not the patient had completed linear growth or had undergone hematopoietic cell transplant, using Wilcoxon Rank Sum or Chi-square, as appropriate., Results: Overall, 60% of children and 58% of adults with FA had short stature, 68% of children and 30% of adults had glucose intolerance, 61% of children and 37% of adults had mild hypothyroidism, and 40% of adults had evidence of hypogonadism (not possible to fully assess in children). In general, bone mineral density (BMD) was normal in adults, while BMD in children was normal when results were adjusted for bone size/thickness using height age., Conclusions: We have evaluated in detail children and adults with FA for their growth and endocrine function. Overall, 79% of children and adults with FA had one or more endocrine abnormality., (Copyright © 2012 Wiley Periodicals, Inc.)
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- 2012
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39. Medullary thyroid cancer in a 9-week-old infant with familial MEN 2B: Implications for timing of prophylactic thyroidectomy.
- Author
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Shankar RK, Rutter MJ, Chernausek SD, Samuels PJ, Mo JQ, and Rutter MM
- Abstract
Background: Patients with Multiple Endocrine Neoplasia type 2 (MEN 2) are at high risk of developing aggressive medullary thyroid carcinoma (MTC) in childhood, with the highest risk in those with MEN type 2B (of whom >95% have an M918T RET proto-oncogene mutation). Metastatic MTC has been reported as young as 3 months of age. Current guidelines recommend prophylactic thyroidectomy within the first year of life for MEN 2B., Patient Findings: We report a 9-week-old infant with MTC due to familial MEN 2B. A full-term male infant, born to a mother with known MEN 2B and metastatic MTC, had an M918T RET proto-oncogene mutation confirmed at 4 weeks of age. He underwent prophylactic total thyroidectomy at 9 weeks of age. Pathology showed a focal calcitonin-positive nodule (2.5 mm), consistent with microscopic MTC., Summary: This case highlights the importance of early prophylactic thyroidectomy in MEN 2B. Although current guidelines recommend surgery up to a year of life, MTC may occur in the first few weeks of life, raising the question of how early we should intervene. In this report, we discuss the risks, benefits and barriers to performing earlier thyroidectomy, soon after the first month of life, and make suggestions to facilitate timely intervention. Prenatal anticipatory surgical scheduling could be considered in familial MEN 2B. Multidisciplinary collaboration between adult and pediatric specialists is key to the optimal management of the infant at risk.
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- 2012
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40. Bone mineral density is normal in children with Fanconi anemia.
- Author
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Rose SR, Rutter MM, Mueller R, Harris M, Hamon B, Bulluck AF, and Smith FO
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Female, Humans, Male, Young Adult, Bone Density, Fanconi Anemia metabolism
- Abstract
Background: Conflicting data exist regarding whether low bone mineral density (BMD) is associated with Fanconi anemia (FA). The current study identified the frequency of low BMD in FA, expecting low BMD even in childhood and before HCT., Procedure: Thirty-seven FA patients (18 prior HCT, 19 no prior HCT), participating in an IRB-approved database, had clinical assessment of DXA of lumbar spine BMD. Four had used androgens, one later underwent HCT. Most had used glucocorticoids after HCT (prolonged in five), and one more with no HCT. BMD [in standard deviation units from mean for age (SD), gender, and ethnicity (BMD Z-score)] was then adjusted for height age, and separately for bone maturation (BA). Data were collected for height SD, pubertal stage, and duration since HCT., Results: BMD Z-score (without adjustment) was <-1 SD in half of FA children. BA-adjusted BMD Z-score was similar. (BA was not usually delayed, although most patients were short.) In contrast, height age-adjusted BMD Z-score was normal in most with FA (only below -2.0 in one child after prolonged glucocorticoids). Mean duration after HCT until DXA test was 6.2 years (median 4.2 years, range 1-18 years)., Conclusions: Children and adolescents with FA have normal BMD prior to and after HCT, when DXA results are adjusted for bone size/height age. In contrast, BA-adjustment of BMD was not useful in this population. Individual BMD results may be influenced by gonadal function, transplantation status, and prolonged glucocorticoid therapy., (Copyright © 2011 Wiley-Liss, Inc.)
- Published
- 2011
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41. Endocrine aspects of Duchenne muscular dystrophy.
- Author
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Bianchi ML, Biggar D, Bushby K, Rogol AD, Rutter MM, and Tseng B
- Subjects
- Adrenal Cortex Hormones physiology, Bone and Bones physiopathology, Female, Growth physiology, Humans, Male, Muscular Dystrophy, Duchenne pathology, Puberty physiology, Weight Gain physiology, Endocrine Glands physiopathology, Muscular Dystrophy, Duchenne physiopathology
- Published
- 2011
- Full Text
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42. Osteoblast-specific expression of insulin-like growth factor-1 in bone of transgenic mice induces insulin-like growth factor binding protein-5.
- Author
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Rutter MM, Markoff E, Clayton L, Akeno N, Zhao G, Clemens TL, and Chernausek SD
- Subjects
- Age Factors, Animals, Animals, Newborn, Gene Expression Regulation physiology, Insulin-Like Growth Factor Binding Protein 5 genetics, Insulin-Like Growth Factor I genetics, Male, Mice, Mice, Transgenic, Osteogenesis physiology, RNA, Messenger biosynthesis, RNA, Messenger genetics, Insulin-Like Growth Factor Binding Protein 5 biosynthesis, Insulin-Like Growth Factor I biosynthesis, Osteoblasts metabolism
- Abstract
The activities of insulin-like growth factors (IGFs) in bone are modulated by a family of binding proteins (IGFBPs) whose physiological roles remain poorly understood. We have previously shown that targeted overexpression of IGF-I in osteoblasts of transgenic (OC-IGF-I) mice stimulates bone formation. In this model, bone formation is markedly but transiently increased in an age-dependent manner, raising the possibility that IGF-I may be influencing IGFBPs to in turn modulate its paracrine actions within bone. We sought to characterize the IGFBPs in normal mouse bone during development and to determine whether osteoblast-targeted overexpression of IGF-I influenced bone IGFBP abundance in vivo. Femoral bone IGFBP content was assessed in control nontransgenic and OC-IGF-I mice by I125-IGF-I ligand and immunoblotting. Bone IGFBP-5 and IGF-I mRNA abundance was determined using real-time reverse transcription (RT)-PCR. Ligand blot of bone extract showed a 30-kDa band, identified as IGFBP-5 by immunoblot, predominated. The abundance of IGFBP-5 declined with age in both control and transgenic bone. Ligand and immunoblot analysis revealed a 5-fold increase in IGFBP-5 protein levels at 3 weeks in transgenic bone (P<0.0001). The elevated IGFBP-5 protein levels were associated with a similar increase in IGF-I mRNA abundance (4-fold, P<0.01) and a significant increase in IGFBP-5 mRNA abundance (1.5-fold). Despite the age-related decline at 6 weeks, IGFBP-5 remained significantly (P<0.01) more abundant in transgenic bone compared to controls. In contrast, bone IGFBP-4 abundance was relatively unchanged by either age or IGF-I overexpression. These studies demonstrate a distinctive developmental pattern of IGFBP-5 content in mouse bone and show that osteoblast-derived IGF-I determines skeletal IGFBP-5 abundance, at least in part by inducing its synthesis. In that IGFBP-5 is thought to stimulate bone formation, directly or via IGF-I action, such changes in bone IGFBP-5 may be important to ensure robust bone acquisition in the early postnatal period.
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- 2005
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43. Idiopathic hypercalcemia and eosinophilic fasciitis: a novel association.
- Author
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Rutter MM, Prahalad S, Passo M, and Backeljauw PF
- Subjects
- Adolescent, Blood Chemical Analysis, Eosinophilia complications, Fasciitis complications, Follow-Up Studies, Humans, Hypercalcemia complications, Male, Risk Assessment, Severity of Illness Index, Treatment Outcome, Eosinophilia diagnosis, Fasciitis diagnosis, Glucocorticoids therapeutic use, Hypercalcemia diagnosis, Hypercalcemia drug therapy
- Abstract
A 15 year-old boy presented with moderate hypercalcemia (serum calcium 3.35 mmol/l) and eosinophilic fasciitis. An extensive search for a cause of hypercalcemia or underlying malignancy proved negative. Glucocorticoid treatment resulted in significant clinical improvement and resolution of the hypercalcemia. This report describes the novel association of hypercalcemia with eosinophilic fasciitis, with potential implications for the role of inflammatory mediators.
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- 2004
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44. Pseudohypoparathyroidism type Ia: late presentation with intact mental development.
- Author
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Rutter MM and Smith EP
- Subjects
- Calcitriol therapeutic use, Calcium blood, Calcium, Dietary therapeutic use, Child, Female, Humans, Mental Status Schedule, Phosphates blood, Pseudohypoparathyroidism blood, Pseudohypoparathyroidism drug therapy, Radiography, Metacarpophalangeal Joint diagnostic imaging, Pseudohypoparathyroidism diagnostic imaging
- Published
- 1998
- Full Text
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