ABSTRACT: Purpose of Review: This article uses a case-based approach to highlight the clinical features as well as recent advances in molecular genetics, muscle imaging, and pathophysiology of the congenital myopathies.
Recent Findings: Congenital myopathies refer to a heterogeneous group of genetic neuromuscular disorders characterized by early-onset muscle weakness, hypotonia, and developmental delay. Congenital myopathies are further classified into core myopathies, centronuclear myopathies, nemaline myopathies, and congenital fiber-type disproportion based on the key pathologic features found in muscle biopsies. Genotype and phenotype correlations are hampered by the diverse clinical variability of the genes responsible for congenital myopathies, ranging from a severe neonatal course with early death to mildly affected adults with late-onset disease. An increasing number of genes have been identified, which, in turn, are associated with overlapping morphologic changes in the myofibers. Precise genetic diagnosis has important implications for disease management, including family counseling; avoidance of anesthetic-related muscle injury for at-risk individuals; monitoring for potential cardiac, respiratory, or orthopedic complications; as well as for participation in clinical trials or potential genetic therapies.
Summary: Collaboration with neuromuscular experts, geneticists, neuroradiologists, neuropathologists, and other specialists is needed to ensure accurate and timely diagnosis based on clinical and pathologic features. An integrated multidisciplinary model of care based on expert-guided standards will improve quality of care and optimize outcomes for patients and families with congenital myopathies.
Address correspondence to Dr Jean K. Mah, Alberta Children’s Hospital, Division of Pediatric Neurology, 2888 Shaganappi Trail NW, Calgary, AB T3B 6A8, Canada, firstname.lastname@example.org.
Relationship Disclosure: Dr Mah has received personal compensation as a consultant for aTyr Pharma and PTC Therapeutics and has received research/grant support as study and site investigator for Alberta Children’s Hospital, Bristol-Myers Squibb, Children’s Hospital of Eastern Ontario, Cooperative International Neuromuscular Research Group, Eli Lilly and Company, FSHD Global Research Foundation, FSH Society, the Hospital for Sick Children, Muscular Dystrophy Canada, Novartis AG, Pfizer Inc, PTC Therapeutics, and Sanofi Genzyme. Dr Joseph has received research/grant support from the Endowed Chair of the University of Calgary to create the brain tissue bank and receives publishing royalties from UpToDate, Inc and Wolters Kluwer. Dr Joseph also gave expert testimony for Alberta Justice, for which he did not receive compensation.
Unlabeled Use of Products/Investigational Use Disclosure: Drs Mah and Joseph report no disclosures.