Prevalence of congenital myopathies in a representative pediatric united states population

Amburgey, Kimberly; McNamara, Nancy; R., Bennett, Lindsey; McCormick, Michael E.; Acsádi, Gyula; Dowling, James J.

doi:10.1002/ana.22510

Cited by 124 publications

(100 citation statements)

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“…Most patients had a genetic diagnosis, with core myopathies and RYR1 mutations, respectively, the most common histopathologic and genetic diagnoses, as reported. 11,13,25 Bearing in mind that the defining features of the CMs (such as FTD, nemaline rods, cores, and central nuclei) are not specific and may occur in other clinical situations, 26 including CNS developmental malformations 27 and recently recognized multisystem disorders with primary autophagy defects, 28,29 we took great care that only patients with clinicopathologic features of a CM without evidence of other underlying conditions were included in this study. The onset of clinical signs was observed predominantly within the first year of life: approximately half of the patients presented in the neonatal period with severe feeding and respiratory complications, as described.…”

Section: Methodsmentioning

confidence: 99%

Congenital myopathies

et al. 2015

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Objective: To assess the natural history of congenital myopathies (CMs) due to different genotypes. Methods:Retrospective cross-sectional study based on case-note review of 125 patients affected by CM, followed at a single pediatric neuromuscular center, between 1984 and 2012.Results: Genetic characterization was achieved in 99 of 125 cases (79.2%), with RYR1 most frequently implicated (44/125). Neonatal/infantile onset was observed in 76%. At birth, 30.4% required respiratory support, and 25.2% nasogastric feeding. Twelve percent died, mainly within the first year, associated with mutations in ACTA1, MTM1, or KLHL40. All RYR1-mutated cases survived and did not require long-term ventilator support including those with severe neonatal onset; however, recessive cases were more likely to require gastrostomy insertion (p 5 0.0028) compared with dominant cases. Independent ambulation was achieved in 74.1% of all patients; 62.9% were late walkers. Among ambulant patients, 9% eventually became wheelchairdependent. Scoliosis of variable severity was reported in 40%, with 1/3 of (both ambulant and nonambulant) patients requiring surgery. Bulbar involvement was present in 46.4% and required gastrostomy placement in 28.8% (at a mean age of 2.7 years). Respiratory impairment of variable severity was a feature in 64.1%; approximately half of these patients required nocturnal noninvasive ventilation due to respiratory failure (at a mean age of 8.5 years). Conclusions:We describe the long-term outcome of a large cohort of patients with CMs. While overall course is stable, we demonstrate a wide clinical spectrum with motor deterioration in a subset of cases. Severity in the neonatal/infantile period is critical for survival, with clear genotype-phenotype correlations that may inform future counseling. Neurology ® 2015;84:28-35 GLOSSARY ACTA1 5 skeletal muscle a-actin; AD 5 autosomal dominant; AR 5 autosomal recessive; CM 5 congenital myopathy; CNM 5 centronuclear myopathy; DNIV 5 daily noninvasive ventilation; DNM2 5 dynamin 2; FTD 5 fiber type disproportion; G/J 5 gastrostomy/jejunostomy; KLHL40 5 kelch-like family member 40; MTM1 5 myotubularin; NEB 5 nebulin; NGT 5 nasogastric tube; NM 5 nemaline myopathy; NNIV 5 nocturnal noninvasive ventilation; NSMC 5 nonspecific myopathic changes; RYR1 5 ryanodine receptor type 1; SEPN1 5 selenoprotein N; TPM2 5 b-tropomyosin; TPM3 5 tropomyosin 3.

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Section: Methodsmentioning

confidence: 99%

Congenital myopathies

et al. 2015

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“…97 Prevalence is estimated to be 1 in 26 000 to 28 000, with mutations in RYR1 (encoding ryanodine receptor 1) being the most prevalent (≈1 in 90 000). 99 Clinically, CMs have been defined recently as "a group of genetic muscle disorders characterized by hypotonia and weakness, usually from birth, and a static or slowly progressive clinical course." 97 Although it can be difficult to distinguish CM from other disorders that present with hypotonia, hyporeflexia, and weakness (eg, DM or congenital muscular dystrophies), the presence of prominent facial weakness with or without ptosis, generalized hypotonic posture with hyporeflexia, poor muscle bulk, proximal muscle weakness, and dysfunction of the respiratory and bulbar muscles are suggestive of CM.…”

Section: Congenital Myopathymentioning

confidence: 99%

Management of Cardiac Involvement Associated With Neuromuscular Diseases: A Scientific Statement From the American Heart Association

Feingold¹,

Mahle²,

Auerbach³

et al. 2017

Circulation

204

188

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For many neuromuscular diseases (NMDs), cardiac disease represents a major cause of morbidity and mortality. The management of cardiac disease in NMDs is made challenging by the broad clinical heterogeneity that exists among many NMDs and by limited knowledge about disease-specific cardiovascular pathogenesis and course-modifying interventions. The overlay of compromise in peripheral muscle function and other organ systems, such as the lungs, also makes the simple application of endorsed adult or pediatric heart failure guidelines to the NMD population problematic. In this statement, we provide background on several NMDs in which there is cardiac involvement, highlighting unique features of NMD-associated myocardial disease that require clinicians to tailor their approach to prevention and treatment of heart failure. Undoubtedly, further investigations are required to best inform future guidelines on NMD-specific cardiovascular health risks, treatments, and outcomes. N euromuscular diseases (NMDs) encompass a broad spectrum of diagnoses with overlapping but distinct phenotypes. Common to many NMDs is cardiac involvement. Although the past 3 decades have seen marked advances in our understanding of many NMDs, significant gaps in knowledge remain on how best to approach cardiac care in these patients. For example, survival in Duchenne muscular dystrophy (DMD) has been extended through the use of glucocorticoid use and respiratory support, yet cardiac complications remain a significant cause of morbidity and mortality.1-3 To achieve further gains in care, we will need to improve our understanding of the pathophysiologies driving cardiac involvement in NMDs and advance treatments aimed at preventing the progression of heart failure (HF) and sudden death in NMDs. The recently published findings of an expert working group on cardiac involvement in DMD, which outlined key gaps in knowledge and made specific recommendations aimed at improving diagnosis and management, are a step toward this goal. 4 In this statement, we include a comprehensive overview of the major categories of NMDs with cardiac involvement. For each, a brief background of the gene defect(s), common clinical manifestations (particularly cardiac findings), and current therapies is summarized. Gaps in knowledge are highlighted, and where possible, clinical treatment suggestions are made by the expert writing group appointed by the American Heart Association to review the available literature. Selection of the writing group was performed in accordance with the American Heart Association's conflict-of-interest management policy. Participants volunteered to write sections relevant to their expertise and experience. CLINICAL STATEMENTS AND GUIDELINESconducted a general search of the literature, restricted to human subjects research published between 1980 and 2016. Drafts of each section were written and sent to the chair of the writing group for incorporation into a single document, which was then edited. The edited document was discussed electron...

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“…It is now clear that RYR1-related myopathies are the most common nondystrophic muscle conditions of childhood and that the clinical spectrum for the disorders is vast [36,37]. One important issue to emerge is how to interpret identified sequence variants in RYR1 that are of uncertain pathogenicity [11,16].…”

Section: What Are Key Current Issues Related To the Disease?mentioning

confidence: 99%

Triadopathies: An Emerging Class of Skeletal Muscle Diseases

2014

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The triad is a skeletal muscle substructure responsible for the regulation of excitation-contraction coupling. It is formed by the close apposition of the T-tubule and the terminal sarcoplasmic reticulum. A rapidly growing list of skeletal myopathies, here referred to as triadopathies, are caused by gene mutations in components of the triad. These disorders, at their root, are caused by defects in excitation contraction coupling and intracellular calcium homeostasis. Secondary abnormalities in triad structure and/or function are also reported in several muscle diseases, most notably certain muscular dystrophies. This review highlights the current understanding of both primary and secondary triadopathies, and identifies important concepts yet to be fully addressed in the field. The emphasis of the review is both on the pathogenesis of triadopathies and their potential treatment.

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Prevalence of congenital myopathies in a representative pediatric united states population

Cited by 124 publications

References 8 publications

Congenital myopathies

Congenital myopathies

Management of Cardiac Involvement Associated With Neuromuscular Diseases: A Scientific Statement From the American Heart Association

Triadopathies: An Emerging Class of Skeletal Muscle Diseases

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