Congenital Muscular Dystrophy Overview – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY

NOTE: THIS PUBLICATION HAS BEEN RETIRED. THIS ARCHIVAL VERSION IS FOR HISTORICAL REFERENCE ONLY, AND THE INFORMATION MAY BE OUT OF DATE.

Clinical characteristics: 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 allelic variants occur, are laminin alpha-2 (merosin) deficiency (MDC1A), collagen VI-deficient CMD, the dystroglycanopathies (caused by mutation of POMT1, POMT2, FKTN, FKRP, LARGE1, POMGNT1, and ISPD), SELENON (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.

Diagnosis/testing: 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.

Genetic counseling: The congenital muscular dystrophies are inherited in an autosomal recessive manner with the following exceptions: collagen VI-deficient CMD, which may be inherited in an autosomal recessive or an autosomal dominant manner; LMNA-related CMD (L-CMD), which is inherited in an autosomal dominant manner with all cases to date caused by a de novo pathogenic variant.

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 pathogenic variants 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 apparent de novo pathogenic variant 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 pathogenic variant has been identified.

Management: Treatment of manifestations: Treatment tailored to an individual’s needs is best managed by a multidisciplinary team. Speech therapy and swallowing studies are used to evaluate those with feeding difficulties and/or possible aspiration. Interventions may be needed for inadequate weight gain and poor feeding. Aspiration pneumonia and/or respiratory insufficiency may require assisted cough devices, supplemental oxygen, noninvasive ventilation, and/or mechanical ventilation via tracheostomy. Physical therapy focuses on stretching exercises of the spine and limbs and to prevent contractures, and positive pressure devices or ventilation to promote mobility of the thoracic cage. Splints, braces and surgical intervention are used to prevent and treat spinal and limb contractures and deformities; these and other assistive devices may help posture, ambulation, and mobility. Epilepsy, behavior problems, and/or intellectual disability require specific treatment and interventions. Vaccinations, early treatment of pulmonary infections, and attention to oral hygiene and care are important aspects of routine care. With support for their physical disabilities the vast majority of children with CMD who have normal cognitive development benefit socially and educationally from mainstreaming into regular educational facilities. The multidisciplinary team can provide social and emotional support for patients and caregivers.

Surveillance: Routine monitoring of feeding and weight gain, respiratory function, strength, and mobility; annual or biannual monitoring for orthopedic and pulmonary complications; cardiac monitoring for those with CMD subtypes involving a risk for cardiomyopathy. Those with CMD subtypes with central nervous system involvement require surveillance for possible seizures and/or behavioral problems.