Genetics and Pathophysiology of Primary Dystonia with Special Emphasis on DYT1 and DYT5

Abstract

DYT1 and DYT5 are early-onset dominant inherited dystonias. DYT1 is caused by mutations of the TOR1A gene, located on 9q34, which causes dysfunction of the D₁ direct pathway or the indirect pathway. Dysfunction of the former causes postural-type and segmental dystonia; the latter causes action-type dystonia. In families with action-type dystonia, there are cases with focal and segmental dystonia. Ages of onset of postural-type dystonia are around 6 years, and 8 to 10 years in cases of action-type dystonia. Focal and segmental dystonia develops in the teens. Mental and psychological functions are preserved. DYT5 is caused by heterozygous mutations of the GCH1 gene, located on 14q22.1-q22.2. Again, mental and psychological functions are preserved. Clinically, there are two types: postural and action. Postural-type dystonia occurs around 6 years of age, with postural dystonia of one leg, and all extremities and trunk muscles are involved by the late teens. Action-type dystonia shows dystonic movements from around 8 to 10 years of age. In both types, all symptoms show diurnal fluctuations that diminish with age and are no longer apparent in the late teens. L-dopa produces dramatic effects, which continue throughout the course of the illness. In both postural and action types, each family or sporadic case has a particular mutation. It remains unclear why specific mutations cause certain age- and gender-specific symptoms.

Keywords

DYT1 - DYT5 - Dopa-Responsive dystonia - Segawa disease - postural-type dystonia - action-type dystonia

• References

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