The genetics of Dystonias

Dystonia is a neurological movement disorder in which sustained muscle contractions cause twisting and repetitive movements or abnormal postures. The disorder may be inherited (primary forms) or caused by other factors such as birth-related or other physical trauma, infection, poisoning (e.g. lead poisoning) or reaction to drugs, particularly neuroleptics (secondary forms). Primary dystonia is suspected to be caused by a pathology of the central nervous system, likely originating in those parts of the brain concerned with motor function, such as the basal ganglia, and the GABA (gamma-aminobutyric acid) producing Purkinje neurons. The precise cause of primary dystonia is unknown. In many cases it may involve some genetic predisposition towards the disorder combined with environmental conditions.

Dystonia may affect various parts of the body and has multiple causes, making classification and diagnosis challenging. Dystonia can be classified by age of onset, cause, or by distribution of the body parts affected. There are currently at least 16 different genetic dystonia syndromes, although only a few genes have actually been isolated. The two identified genes for primary dystonia are TOR1A (DYT1 form on chromosome 9) and THAP1 (DYT6 form on chromosome 8). Dystonia are complex diseases with incomplete penetrance and large spectrum of clinical severity.

We have developed, since 2004, research projects on focal and generalized primary dystonia. Our aim is to participate in the  identification of the molecular basis of these disorder by two approaches: