Congenital muscular dystrophy (CMD) is a clinically and genetically heterogeneous group of inherited muscle disorders. Muscle weakness typically presents from birth to early infancy. Affected infants typically appear "floppy" with low muscle tone and poor spontaneous movements. Affected children may present with delay or arrest of gross motor development together with joint and/or spinal rigidity. Muscle weakness may improve, worsen, or stabilize in the short term; however, with time progressive weakness and joint contractures, spinal deformities, and respiratory compromise may affect quality of life and life span. The main CMD subtypes, grouped by involved protein function and gene in which causative mutations occur, are laminin alpha-2 (merosin) deficiency (MDC1A), collagen VI-deficient CMD, the dystroglycanopathies (caused by mutations in POMT1, POMT2, FKTN, FKRP, LARGE, POMGNT1, and ISPD), SEPN1-related CMD (previously known as rigid spine syndrome, RSMD1) and LMNA-related CMD (L-CMD). Several less known CMD subtypes have been reported in a limited number of individuals. Cognitive impairment ranging from intellectual disability to mild cognitive delay, structural brain and/or eye abnormalities, and seizures are found almost exclusively in the dystroglycanopathies while white matter abnormalities without major cognitive involvement tend to be seen in the laminin alpha-2-deficient subtype.
The diagnosis of congenital muscular dystrophy relies on clinical findings, brain and muscle imaging, muscle biopsy histology (dystrophic features without the hallmarks of the structural changes seen in the congenital myopathies), muscle and/or skin immunohistochemical staining, and molecular genetic testing.
The congenital muscular dystrophies are inherited in an autosomal recessive manner with the exception of collagen VI-deficient CMD which may be inherited in an autosomal recessive or an autosomal dominant manner and LMNA-related CMD (L-CMD) which is inherited in an autosomal dominant manner with all cases to date caused by de novo mutation. In autosomal recessive subtypes, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carriers are asymptomatic. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if the disease-causing mutations in the family are known. In autosomal dominant subtypes, the offspring of affected individuals have a 50% chance of being affected. The risk to sibs of an individual with an apparently de novo mutation is low, but not zero because of the possibility of germline mosaicism in one of the parents. Prenatal testing for pregnancies at increased risk is possible for families in which the disease-causing mutation has been identified.