Myoclonus-dystonia

Primary dystonias, particularly DYT1 dystonia, may be associated with brief, myoclonic muscle jerks. However, researchers have described a distinct genetic disorder in which dystonia may be associated with marked, rapid, "lightening-like" myoclonus. Currently known as "myoclonus-dystonia" or "inherited myoclonus-dystonia syndrome," the disorder is characterized by variable combinations of dystonia and myoclonus without other signs or symptoms of neurologic dysfunction (e.g., seizures, dementia, or impaired coordination of voluntary movements [ataxia]). As mentioned earlier, myoclonus refers to sudden, involuntary, "shock-like" muscle contractions, often accompanied by periodic interruptions in voluntary muscle contraction (muscle inhibition). Many researchers suggest that myoclonus-dystonia may represent the same disease entity as so-called "hereditary essential myoclonus," a usually familial disorder in which myoclonus is an isolated or primary finding often occurring in association with dystonia.

In patients with myoclonus-dystonia, associated symptoms usually become apparent during childhood or adolescence, although onset may occur during adulthood. Myoclonus is often the most prominent feature, primarily affecting muscles of the arms, shoulders, neck, and trunk and usually sparing the face and legs. The myoclonic jerks typically occur or worsen with voluntary movement (action myoclonus) and may be exacerbated by stress or fatigue. In addition, in many patients, consumption of alcohol may alleviate myoclonus; however, a "rebound" worsening of symptoms has sometimes been described subsequent to alcohol intake.

In addition to myoclonus, some affected individuals may also develop abnormal dystonic movements and postures. Myoclonic jerks and dystonic spasms may affect the same muscle groups or occur independently of one another. Various forms of dystonia have been reported in affected family members, including upper limb, cranial, cervical, and trunk dystonia. Rarely, dystonia may be the sole finding associated with the disorder.

The course of myoclonus-dystonia is usually relatively benign. In members of some families, the dystonia or myoclonus may appear to spontaneously subside (remission). However, in most patients, symptoms gradually progress for a few years and then tend to stabilize with periodic fluctuations or have mild spontaneous improvement.

Myoclonus-dystonia is transmitted as an autosomal dominant trait that appears to have reduced penetrance and variable expressivity, with males more commonly affected (in contrast to DRD). Genetic analysis of one family with 8 affected members demonstrated mutations of the gene that regulates production of the D2 dopamine receptor (DRD2) protein. The genetic locus (designated DYT11) has been mapped to chromosome 11q23. Further research is needed to determine whether all families with myoclonus-dystonia (and the entity known as hereditary essential myoclonus) are indeed affected by the same genetic disorder.

	Heredodegenerative Dystonia