Duchenne's Muscular Dystrophy

X-linked recessive mutation of the dystrophin gene that affects males almost exclusively. Progressive weakness in hip and shoulder girdle muscles beginning by age 5; by age 12, the majority were nonambulatory in the era prior to the use of glucocorticoids. Survival beyond age 25 is rare. Associated problems include tendon and muscle contractures, progressive kyphoscoliosis, impaired pulmonary function, cardiomyopathy, and intellectual impairment. Palpable enlargement and firmness of some muscles. Becker dystrophy is a less severe form, with a slower course and later age of onset (usually 5-15 years) but similar clinical, laboratory, and genetic features.

Laboratory findings include massive elevations (20-100 × normal) of serum CK, a myopathic pattern on EMG testing, and evidence of groups of necrotic muscle fibers with regeneration, phagocytosis, and fatty replacement of muscle on biopsy. Diagnosis is established by determination of dystrophin deficiency in peripheral blood; muscle biopsy is now rarely needed. Testing is available for detecting carriers and prenatal diagnosis. Dystrophin is part of a large complex of muscle membrane glycoproteins, disruption of which weakens the cell membrane.

Limb-Girdle Dystrophy

A constellation of diseases with proximal weakness involving the pelvic and shoulder girdle musculature. Age of onset, rate of progression, severity of manifestations, inheritance pattern (autosomal dominant or autosomal recessive), and associated complications (e.g., cardiac, respiratory) vary with the specific subtype of disease.

Myotonic Dystrophy

Type 1 is an autosomal dominant disorder with genetic anticipation. Weakness typically becomes obvious in the second to third decade and initially involves the muscles of the face, neck, and distal extremities. This results in a distinctive facial appearance (“hatchet-faced”) with ptosis, temporal wasting, drooping of the lower lip, and sagging of the jaw. Myotonia manifests as an inability to relax muscles rapidly following a strong exertion (e.g., after tight hand grip) usually by the age of 5, and by sustained contraction of muscles following percussion (e.g., of tongue or thenar eminence).

Associated findings can include frontal baldness, posterior subcapsular cataracts, gonadal atrophy, respiratory and cardiac problems, endocrine abnormalities, intellectual impairment, and hypersomnia. Cardiac disturbances, including complete heart block, may be life-threatening. Respiratory function should be carefully followed, as chronic hypoxia may lead to cor pulmonale.

Laboratory studies show normal or mildly elevated CK, characteristic myotonia and myopathic features on EMG, and a typical pattern of muscle fiber injury on biopsy. Myotonic dystrophy type 1 is caused by an unstable expansion of a CTG trinucleotide repeat in a protein kinase gene (named DMPK) on chromosome 19q13.3. Genetic testing for early detection and prenatal diagnosis is possible.

Facioscapulohumeral (Fsh) Dystrophy

An autosomal dominant, slowly progressive disorder with onset in childhood or young adulthood. Weakness involves facial (usually the initial manifestation), shoulder girdle, and proximal arm muscles and can result in atrophy of biceps, triceps, and scapular winging. Facial weakness results in inability to smile, whistle, or fully close the eyes. Foot drop and leg weakness may cause falls and progressive difficulty with ambulation.

Laboratory studies reveal normal or slightly elevated CK and usually myopathic features on EMG and muscle biopsy. Type 1 FSD is caused by deletions at chromosome 4q35 leading to toxic expression of the DUX4 gene. Genetic testing is available for carrier detection and prenatal diagnosis.

Oculopharyngeal Dystrophy

Onset in the fourth to sixth decade of ptosis, limitation of extraocular movements, and facial and cricopharyngeal weakness. One of several disorders characterized by progressive external ophthalmoplegia (CPEO). Dysphagia may be life-threatening. Most pts are of French-Canadian or Spanish-American descent. Mutation in a poly-RNA binding protein responsible.