Myotonic dystrophy: Encyclopedia II - Myotonic dystrophy - Overview

Myotonic dystrophy - Overview

Myotonic dystrophy (DM) is the most common muscular dystrophy in adults, and is the second most common muscular dystrophy after Duchenne muscular dystrophy. It is an autosomal dominant genetic disorder affecting one in 8,000 individuals. Onset is usually in the second or third decade and the life span of affected individuals is typically six decades. A congenital form of DM can occur in second or third generations, however, and can be fatal for affected infants. Characteristics of DM include myotonia, as well as progressive weakening and wasting of the voluntary muscles of the eyes, face, neck, arms and legs. Muscles related to involuntary activities such as swallowing and breathing, as well as those surrounding the internal organs such as the upper and lower digestive tracts may also be affected. The gall bladder, and the uterus may also be affected as the disease progresses in an individual. Other characteristics include cataracts, cardiac conduction abnormalities, cognitive deficits, and frontal balding.

The genetic causes of three forms of DM have been identified:

• DM1, also known as Steinert's disease
• DM2, also known as proximal myotonic myopathy (PROMM)
• Congenital myotonic dystrophy (CMyD)

DM1 and DM2 have similar clinical presentations, however, DM2 may present with milder symptoms. Both DM1 and DM2 are equally prevalent. CMyD is the most serious form of DM. Affected infants typically have severe muscle weakness, hypotonia and difficulties with breathing, sucking and swallowing. Intensive clinical intervention is necessary to improve the chance of survival of such children. CMyD and early onset DM1 are attributable to the phenomenon of anticipation. The abnormal nucleotide repeat expansion that has been identified as the cause of DM1 can lengthen in successive generations, which lowers the age of onset and increases symptom severity.

All three forms of DM are caused by an abnormal nucleotide repeat expansion. In DM1 and CMyD, the expansion is in a non-coding region of the DMPK (Dystrophia-myotonica protein kinase) gene on chromosome 19. In DM2, the expansion is in a non-coding region of the ZNF9 (zinc finger protein 9) gene on chromosome 3. The fact that both repeat expansions occur in non-coding regions of these genes, yet result in very similar multi-systemic symptoms, has led researchers to hypothesize that mutant RNA is a contributing factor to DM.

Adapted from the Wikipedia article "Overview", under the G.N U Free Docmentation License. Please also see http://en.wikipedia.org/wiki