Muscular Dystrophy with Neurologic Involvement

Several muscular dystrophies extend beyond skeletal muscle to involve the central nervous system creating complex multisystem disorders. Dystrophinopathies including Duchenne and Becker muscular dystrophy result from dystrophin gene mutations and may present with cognitive impairment learning disabilities and autism spectrum features in significant proportion of patients. Brain dystrophin isoforms underlie this neurologic involvement.

Myotonic dystrophy type 1 caused by CTG repeat expansion in the DMPK gene presents with multisystem involvement including muscle weakness myotonia cataracts cardiac conduction abnormalities and prominent central nervous system features. Cognitive dysfunction excessive daytime sleepiness apathy and white matter abnormalities are characteristic. Severity correlates with repeat length particularly in congenital form. FKRP related dystroglycanopathies cause varying brain involvement from severe lissencephaly type cobblestone cortex to milder cognitive impairment.

Evaluation requires multidisciplinary approach including neurology genetics cardiology pulmonology and developmental specialists. Brain MRI identifies structural abnormalities including cortical malformations white matter changes and atrophy. Neuropsychological assessment guides educational and behavioral interventions. Cardiac evaluation including echocardiography and rhythm monitoring is essential as cardiac involvement contributes significantly to morbidity and mortality. Genetic counseling helps families understand inheritance patterns and reproductive options. Emerging therapies including exon skipping for Duchenne and antisense oligonucleotides offer new treatment options requiring specialized centers.