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Muscular dystrophy 

Muscular dystrophy

Muscular dystrophy

K. Bushby



Limb girdle muscular dystrophy—description of LGMD2L.

Updated on 28 Nov 2012. The previous version of this content can be found here.
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date: 23 April 2017

Muscular dystrophies are primary, genetically determined, disorders of muscle. All cause muscle weakness, which is usually progressive. They are challenging to classify, but clinical characteristics can be combined with genetic and molecular information to obtain a useful operational nomenclature for prognosis and family counselling. In general, diagnosis is guided by the age at which clinical manifestations appear and the rate at which muscle function is lost, but unusual features such as muscle pain and rhabdomyolysis may also contribute to the identification of a particular hereditary muscle disorder.

Congenital muscular dystrophies

These are defined by their very early childhood onset. Molecularly based subclassification allows the recognition of various subgroups including those associated with mutations in/causing: (1) laminin A2, (2) abnormal glycosylation of α‎-dystroglycan; (3) collagen VI—Ullrich congenital muscular dystrophy, (4) selenoprotein 1 gene, (5) other genes with variable presentation, including CMD such as mutations in lamin A/C.

Dystrophin deficiency

Duchenne and Becker muscular dystrophy are X-linked diseases that are both caused by mutations (mostly deletions) in the dystrophin gene.

Clinical features—(1) Duchenne muscular dystrophy—all affected boys are symptomatic within the first 3 years of life, although diagnosis is frequently delayed beyond this; motor milestones and speech are frequently delayed; there is a pronounced waddling gait on attempting to run. Hypertrophy of the calf muscles is almost universal. (2) Becker muscular dystrophy—mean age at onset is 11 years; typically manifests with difficulty with high steps and climbing hills; may suffer muscle pain after exercise; frequently have hypertrophy involving the same muscle groups as seen in Duchenne muscular dystrophy.

Investigation, diagnosis and prevention—serum creatine kinase is always massively elevated, but the level does not distinguish the severity of the disease. Molecular confirmation of the diagnosis is essential to assist in defining prognosis and allow provision of appropriate genetic counselling.

Prognosis and complications—the prognosis of ‘dystrophinopathies’ is highly variable. Untreated patients with Duchenne muscular dystrophy lose the ability to walk by the age of 12, but corticosteroids can delay deterioration. Scoliosis, respiratory failure and cardiomyopathy develop during the teenage years. With appropriate multidisciplinary supportive care, survival into or beyond the late twenties and thirties is becoming more common. Novel therapeutics directed to the mutations in the dystrohpin gene are a prospect for treatments in the future.

Other muscular dystrophies

Facioscapulohumeral muscular dystrophy is an autosomal dominant disease sometimes arising as the result of a new dominant mutation, affected individuals manifest early symptoms, typically including facial weakness, shoulder girdle weakness and foot drop, by their teens or twenties. Serum creatine kinase may be normal or mildly elevated. Diagnosis can be confirmed in 95% of cases by demonstration of a deletion close to the telomere of chromosome 4q: more complex analysis is required for the other cases. The condition is slowly progressive; complications rarely include scoliosis and respiratory failure.

Emery–Dreifuss muscular dystrophy—caused by mutation of any one of several genes encoding components of the nuclear envelope (e.g. emerin, lamin A/C). May present at any age, with contractures of the ankles and elbows and rigidity of the spine often predating any clear weakness. Prognosis is determined by ability to manage life-threatening cardiac arrhythmias.

Limb girdle muscular dystrophies—these comprise a range of disorders that cause weakness of the proximal musculature. Important considerations in any case are (1) could it be a dominant disease?—e.g. limb girdle muscular dystrophy 1B (allelic with autosomal dominant Emery–Dreifuss muscular dystrophy), Bethlem myopathy; (2) age of presentation and of rate of progression—these give important clues to likely diagnosis; (3) investigations—creatine kinase is greatly elevated in all forms of autosomal recessive limb girdle muscular dystrophy; EMG confirms a primary myopathic process; muscle biopsy shows dystrophic changes on standard analysis, with more specialized testing for diagnosis of e.g. sarcoglycanopathies, calpainopathy, dysferlinopathy.

Oculopharyngeal muscular dystrophy—typically presents in the sixth decade with ptosis, dysphagia to solids, and dysphonia. Associated with an expanded triplet repeat in the gene for poly(A) binding protein 2.

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