Muscular dystrophy

Muscular dystrophies (MD) are a genetically and clinically heterogeneous group of rare neuromuscular diseases that cause progressive weakness and breakdown of skeletal muscles over time.^[1] The disorders differ as to which muscles are primarily affected, the degree of weakness, how fast they worsen, and when symptoms begin.^[1] Some types are also associated with problems in other organs.^[2]

Over 30 different disorders are classified as muscular dystrophies.^[1][2] Of those, Duchenne muscular dystrophy (DMD) accounts for approximately 50% of cases and affects males beginning around the age of four.^[1] Other relatively common muscular dystrophies include Becker muscular dystrophy, facioscapulohumeral muscular dystrophy, and myotonic dystrophy,^[1] whereas limb–girdle muscular dystrophy and congenital muscular dystrophy are themselves groups of several – usually extremely rare – genetic disorders.

Muscular dystrophies are caused by mutations in genes, usually those involved in making muscle proteins.^[2] The muscle protein, dystrophin, is in most muscle cells and works to strengthen the muscle fibers and protect them from injury as muscles contract and relax.^[3] It links the muscle membrane to the thin muscular filaments within the cell. Dystrophin is an integral part of the muscular structure. An absence of dystrophin can cause impairments: healthy muscle tissue can be replaced by fibrous tissue and fat, causing an inability to generate force.^[4] Respiratory and cardiac complications can occur as well. These mutations are either inherited from parents or may occur spontaneously during early development.^[2] Muscular dystrophies may be X-linked recessive, autosomal recessive, or autosomal dominant.^[2] Diagnosis often involves blood tests and genetic testing.^[2]

There is no cure for any disorder from the muscular dystrophy group.^[1] Several drugs designed to address the root cause are currently available including gene therapy (Elevidys), and antisense drugs (Ataluren, Eteplirsen etc.).^[2] Other medications used include glucocorticoids (Deflazacort, Vamorolone); calcium channel blockers (Diltiazem); to slow skeletal and cardiac muscle degeneration, anticonvulsants to control seizures and some muscle activity, and Histone deacetylase inhibitors (Givinostat) to delay damage to dying muscle cells.^[1] Physical therapy, braces, and corrective surgery may help with some symptoms^[1] while assisted ventilation may be required in those with weakness of breathing muscles.^[2]

Outcomes depend on the specific type of disorder.^[1] Many affected people will eventually become unable to walk^[2] and Duchenne muscular dystrophy in particular is associated with shortened life expectancy.

Muscular dystrophy was first described in the 1830s by Charles Bell.^[2] The word "dystrophy" comes from the Greek dys, meaning "no, un-" and troph- meaning "nourish".^[2]