Chapter 51 Muscular Dystrophy
PATHOPHYSIOLOGY
The muscular dystrophies constitute a group of muscle diseases characterized by severe muscle weakness and atrophy, elevation of serum muscle enzyme levels, and destructive changes of muscle fibers. Affected muscles pseudohypertrophy, and the muscle tissue is replaced by connective tissue and fatty deposits. The traditional classification into Duchenne’s muscular dystrophy (DMD), Becker’s muscular dystrophy, limb-girdle dystrophies, and congenital dystrophies has become more precise with advances in genetics and the ability to identify specific defective proteins.
The most common form of muscular dystrophy (MD), Duchenne’s, is a sex-linked recessive disorder, with mutation of the dystrophin gene and deficiency or absence of dystrophin in skeletal muscle. Onset of symptoms is between 3 to 5 years of age. It is characterized by progressive involvement of voluntary muscles: clumsy gait, lordotic posture, calf hypertrophy, and toe walking are early manifestations. Children with DMD rarely live beyond 20 years of age without mechanical ventilatory support.
Becker’s MD is a sex-linked recessive disorder that involves a reduction in dystrophin, and it is the second most common form. Onset is between 5 and 15 years of age, with survival into the fourth or fifth decade.
Emery-Dreifuss muscular dystrophy (EDMD) has two genetic forms, an X-linked recessive form and a less common autosomal dominant one. EDMD is associated with mutations in emerin, a nuclear membrane protein. Symptoms begin within the first 2 decades of life. Muscle wasting of the biceps and triceps occurs and progresses to include pectoral and pelvic muscles. Typically early development of contractures and cardiac conducton defects occurs.
Limb-girdle muscular dystrophies may be autosomal dominant, autosomal recessive, or congenital. Diagnosis is made by identifying the missing protein with muscle biopsy. Symptoms are a slow onset of progressive muscle weakness; the age of onset varies.
Fascioscapulohumeral muscular dystrophy is the third most common type of MD; it usually begins in the second decade of life. It is an autosomal dominant disease. Muscle biopsy results vary. Clinical symptoms include the classic scapular winging as a result of early weakness of the scapular muscles.
INCIDENCE
1. DMD affects 1 of every 3000 boys (X-linked recessive). Rarely, girls can be affected.
2. DMD accounts for approximately 50% of all cases of muscular dystrophy.
3. Becker’s MD affects boys and occurs in approximately 1 in 30,000 to 40,000 male births. Limb-girdle MD has approximately the same incidence.
4. Fascioscapulohumeral MD affects both sexes.
5. Approximately 30% of the sisters of boys with muscular dystrophy will be carriers, and one half of their male offspring will inherit the disease.
6. Learning disabilities and mild mental retardation are not uncommon in MD.
7. Female carriers of DMD are at risk of developing cardiomyopathy and require periodic cardiovascular screening.
CLINICAL MANIFESTATIONS
Symptoms are related to the voluntary muscles that are affected. The most frequently occurring symptoms are the following:
3. Waddling gait or toe walking
4. Gowers’ sign (hands “climbing” up legs when arising from sitting position)
5. Difficulty running, clumsiness
6. Difficulty lifting arms above head owing to involvement of shoulder girdle muscles
7. Often, loss of ambulation by age 8 to 12 years (Duchenne’s) or 40 years (Becker’s)
8. Pseudohypertrophy, particularly of calf muscles, giving a hard, “woody” appearance
9. Occurrence of scoliosis after child becomes wheelchair dependent
