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Muscular
dystrophies are inherited, progressive muscle disorders resulting
from defects in one or more genes needed for normal muscle function.
They are distinguished by the selective distribution of weakness
and the specific nature of the genetic abnormality involved.
Duchenne dystrophy is the most common and severe form of muscular dystrophy. Becker dystrophy, although closely related, has a later onset and causes milder symptoms. Other forms include Emery-Dreifuss dystrophy, myotonic dystrophy, limb-girdle dystrophy, facioscapulohumeral dystrophy, and congenital dystrophies.
Duchenne
Muscular Dystrophy and Becker Muscular Dystrophy
Duchenne
muscular dystrophy and Becker muscular dystrophy are X-linked recessive
disorders characterized by progressive proximal muscle weakness
caused by muscle fiber degeneration. Becker dystrophy has later
onset and produces milder symptoms. Diagnosis is suggested clinically
and is confirmed by analysis of the protein product (dystrophin)
of the mutated gene. Treatment focuses on maintaining function through
physical therapy and the use of braces and orthotics; prednisone
is given to some patients with severe functional decline.
Duchenne dystrophy and Becker dystrophy are caused by mutations at the Xp21 locus. In Duchenne dystrophy, this mutation results in the severe absence (< 5%) of dystrophin, a protein in the muscle cell membrane. In Becker dystrophy, the mutation results in production of abnormal dystrophin or less dystrophin. Duchenne dystrophy affects 1/3000 live male births. Becker dystrophy affects 1/30,000 live male births. Female carriers may have asymptomatic elevated CK levels and possibly calf hypertrophy.
Symptoms and Signs
Duchenne dystrophy:
This disorder manifests typically between ages 2 and 3 yr. Weakness affects proximal muscles, typically in the lower limbs initially. Children frequently toe walk and have a waddling gait and lordosis. They fall frequently and have difficulty running, jumping, climbing stairs, and rising from the floor. Progression of weakness is steady, and limb flexion contractures and scoliosis develop. Firm pseudohypertrophy (fatty and fibrous replacement of certain enlarged muscle groups, notably the calves) develops. Most children are confined to a wheelchair by age 12 and die of respiratory complications by age 20. Cardiac involvement is usually asymptomatic, although 90% of patients have ECG abnormalities. One third have mild, nonprogressive intellectual impairment that affects verbal ability more than performance.
Becker dystrophy:
This disorder typically becomes symptomatic much later and is milder. Ambulation is usually preserved until at least age 15, and many children remain ambulatory into adulthood. Most affected children survive into their 30s and 40s.
Diagnosis
Diagnosis is suspected by characteristic clinical findings, age at onset, and family history suggestive of X-linked recessive inheritance. Myopathic changes are noted on electromyography (rapidly recruited, short duration, low-amplitude motor unit potentials) and muscle biopsy (necrosis and marked variation in muscle fiber size not segregated by motor unit). CK levels are elevated to up to 100 times normal.
Diagnosis is confirmed by analysis of dystrophin with immunostaining of biopsy samples. Dystrophin is undetectable in patients with Duchenne dystrophy. In patients with Becker dystrophy, dystrophin is typically abnormal (lower molecular weight) or present in low concentration. Mutation analysis of DNA from peripheral blood leukocytes can also confirm the diagnosis by identifying abnormalities in the dystrophin gene (deletions or duplications in about 65% and point mutations in about 25% of patients).
Carrier detection and prenatal diagnosis are possible by using conventional studies (eg, pedigree analysis, CK determinations, fetal sex determination) combined with recombinant DNA analysis and dystrophin immunostaining of muscle tissue.
Treatment
No specific treatment exists. Moderate exercise is encouraged for as long as possible. Passive exercises may extend the period of ambulation. Ankle-foot orthoses help prevent flexion during sleep. Leg braces may temporarily help preserve ambulation or standing. Obesity should be avoided; caloric requirements are likely to be less than normal. Genetic counseling is indicated (see Prenatal Genetic Counseling and Evaluation).
Daily prednisone does not cause significant long-term clinical improvement, but it possibly slows the course of the disease. No consensus on long-term effectiveness exists. Gene therapy is not yet available. Corrective surgery is sometimes needed. Respiratory insufficiency may be treated with noninvasive ventilatory support (eg, nasal mask—see Respiratory Failure and Mechanical Ventilation: Status asthmaticus (SA)). Elective tracheotomy is gaining acceptance, allowing children with Duchenne dystrophy to live into their 20s.
Other Forms
of Muscular Dystrophy
Emery-Dreifuss
dystrophy:
This disorder can be inherited as an autosomal dominant, autosomal recessive (the rarest), or X-linked recessive disorder. The overall incidence is unknown. Females can be carriers, but only males are affected clinically by X-linked inheritance. Genes associated with Emery-Dreifuss dystrophy encode for the nuclear membrane proteins lamin A/C (autosomal) and emerin (X-linked).
Muscle weakness and wasting can begin any time before age 20 and commonly affect the biceps and triceps and, less often, distal leg muscles. The heart is frequently involved, with atrial paralysis, conduction abnormalities (atrioventricular block), cardiomyopathy, and a high likelihood of sudden death.
Diagnosis is indicated by clinical findings, age at onset, and family history. The diagnosis is supported by mildly increased serum CK levels and myopathic features on electromyography and muscle biopsy and is confirmed by DNA testing.
Treatment involves therapy to prevent contractures. Cardiac pacemakers are sometimes lifesaving in patients with abnormal conduction.
Myotonic
dystrophy:
Myotonic dystrophy, the most common form of muscular dystrophy among whites, affects about 30/100,000 live male and female births. Inheritance is autosomal dominant with variable penetrance. Two genetic loci—DM 1 and DM 2—cause the abnormality. Symptoms and signs begin during adolescence or young adulthood and include myotonia (delayed relaxation after muscle contraction), weakness and wasting of distal limb muscles (especially in the hand) and facial muscles (ptosis is especially common), and cardiomyopathy. Intellectual disability, cataracts, and endocrine disorders can also occur.
Diagnosis is indicated by characteristic clinical findings, age at onset, and family history and is confirmed by DNA testing. Treatment includes braces for foot drop and drug therapy for myotonia (eg, mexiletine 75 to 150 mg po bid or tid).
Limb-girdle
dystrophy:
Limb-girdle dystrophy currently has 21 known subtypes, 15 autosomal recessive and 6 autosomal dominant. The overall incidence is unknown. Males and females are affected equally. Several chromosomal loci have been identified for autosomal dominant (5q [no known gene product]) and recessive (2q, 4q [beta-sarcoglycan], 13q [gamma-sarcoglycan], 15q [calpain, a Ca-activated protease], and 17q [alpha-sarcoglycan or adhalin]) forms. Structural (eg, dystrophin-associated glycoproteins) or nonstructural (eg, proteases) proteins can be affected.
Symptoms involve weakness in a limb girdle and proximal limb distribution. Onset of symptoms ranges from early childhood to adulthood; autosomal recessive cases tend to have childhood onset and primarily have a pelvic girdle distribution.
Diagnosis is indicated by characteristic clinical findings, age at onset, and family history and requires muscle histology, immunocytochemistry, Western blot analysis, and genetic testing for specific proteins.
Treatment focuses on prevention of contractures.
Facioscapulohumeral
dystrophy:
Facioscapulohumeral dystrophy is an autosomal dominant disorder characterized by weakness of the facial muscles and shoulder girdle, usually beginning at age 7 to 20. Onset is during adolescence or young adulthood and is characterized by slow progression and difficulty whistling, closing the eyes, and raising the arms (due to weakness of the scapular stabilizer muscles). Life expectancy is normal. An infantile variety, characterized by facial, shoulder, and hip girdle weakness, is rapidly progressive.
Diagnosis is indicated by characteristic clinical findings, age at onset, and family history and is confirmed by DNA testing.
Treatment consists of physical therapy.
Congenital
muscular dystrophy:
Congenital muscular dystrophy is not a single disorder but instead refers to muscular dystrophy evident at birth, occurring from any of several rare forms of muscular dystrophy. The diagnosis is suspected in any floppy neonate but must be distinguished from congenital myopathy by muscle biopsy.
Treatment consists of physical therapy, which may help preserve function.
Last full review/revision August 2009 by Michael Rubin, MD
Content last modified August 2009
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