27th June 2023

Muscular dystrophies

Muscular dystrophies are a group of inherited myopathies, including Duchenne muscular dystrophy, Becker muscular dystrophy and myotonic dystrophy.

Duchenne and Becker muscular dystrophy

Duchenne and Becker muscular dystrophies are caused by mutations in the dystrophin gene. They are inherited in an X-linked recessive manner. Occasionally females can be affected (due to translocation of short arm of chromosome Xp21). The main symptom is progressive weakness, and an elevation of creatinine kinase is noted.

Duchenne’s (DMD) is the more severe form and there is absence of the dystrophin protein. It presents with progressive weakness from ages 3-4. Sufferers also have cardiomyopathy, conduction defects, bone fractures and scoliosis. In some cases, there will be intellectual impairment. On examination, there is the classic pseudohypertrophy of the calf, lumbar lordosis and waddling gait, hypo or areflexia. There is no cure; sufferers are often confined to a wheelchair by age 12-13 and death from cardiorespiratory failure occurs by mid 20s.

Becker’s (BMD) is a milder form as although the dystrophin protein is present, it is dysfunctional and at lower levels than normal. Symptoms usually occur at a later age (usually after the age of 5). They are usually ambulatory well into adult life, requiring wheelchairs at around 50 years of age, although this can vary. Cardiomyopathies can still occur, but intellectual impairment is rare.

Myotonic dystrophy

Myotonic dystrophy (also known as dystrophia myotonica) is inherited in an autosomal dominant manner, and there are two major forms, DM1 and DM2, caused by CTG expansion in dystrophia myotonica protein kinase gene on chromosome 19q, or CCTG expansion in intron 1 of ZNF9 gene on chromosome 3q21.3 respectively.

Myotonic dystrophy has a multisystemic range of symptoms, including skeletal muscle weakness, myotonia (delay in muscle relaxation post contraction), cardiac conduction abnormalities, diabetes mellitus, cataracts, myotonic facies and cognitive impairment. DM1 can present congenitally (which can lead to death in the neonatal period), in childhood, or in ‘classic’ form, where symptoms manifest in the 2nd or 3rd decade of life. DM2 usually begins after the 2nd decade of life and is generally less severe than the classic DM1. Within 10-20 years, severe disability develops, and there is no cure. Symptomatic treatment with phenytoin for myotonia has been used.