Facioscapulohumeral muscular dystrophy
Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant form of muscular dystrophy that initially affects muscles of the face (facio), scapula (scapulo) and upper arms (humeral). It is the third most most common genetic disease of skeletal muscle. Symptoms may develop in early childhood and are usually noticeable in the teenage years with 95% of affected individuals manifesting disease by age 20 years. A progressive skeletal muscle weakness usually develops in other areas of the body as well; often the weakness is asymmetrical. Life expectancy is normal, but up to 15% of affected individuals become severely disabled and eventually must use a wheel chair. more...
Non-muscular symptoms frequently associated with FSHD include subclinical sensorineural hearing loss and retinal telangectasias. The pathophysiology of FSHD is not known. Muscle histologic changes are nonspecific for the muscle wasting. There is evidence of early inflammatory changes in the muscle, but reported responses to high dose open labeled corticosteroid treatment have been negative. Animal studies of anabolic effects of beta adrenergic agonists on models of muscle wasting led to an open trial of albuterol (a beta adrenergic agonist) in which limited preliminary results support an improvement of muscle mass and strength in FSHD. Preliminary studies of muscle cultures suggest an increased sensitivity to oxidative stress, but require further exploration.
More than 95% of cases of FSHD are associated with the deletion of integral copies of a tandemly repeated 3.3kb unit (D4Z4 repeat) at the subtelomeric region 4q35. Inheritance is autosomal dominant, though up to one-third of the cases appear to be the result of de novo (new) mutations. The deletion appears to result in global dislocation of gene expression. If the entire region is removed, there are birth defects, but no specific defects on skeletal muscle. Individuals appear to require the existence of 11 or fewer repeat units to be at risk for FSHD. Though the nature of the DNA mutation is known, it has not been possible to identify a gene or mechanism that causes FSHD and a novel position effect has been postulated to explain the disease phenotype. In addition, some cases of FSHD are the result of rearrangements between subtelomeric chromosome 4q and a subtelomeric region of 10q that contains a tandem repeat structure highly homologous (95%) to 4q35. Disease occurs when the translocation results in a critical loss of tandem repeats to the 4q site. Finally, there is a large family with a phenotype indistinguishable from FSHD in which no pathological changes at the 4q site or translocation of 4q-10q are found.
Read more at Wikipedia.org