The Genetics of Segawa Disease

Abstract

Segawa disease is a dopa-responsive generalized dystonia, caused by abnormalities of the gene GCH-1 located on chromosomes 14q22.1–q22.2. Clinically, there are two types, postural type and action type, depending on the family. Cases of action type show focal or segmental dystonia after adolescence. In families of action type, there are cases starting with focal or segmental dystonia in adulthood or parkinsonism in older age. Both types show symptoms of dopamine decrement due to the deficiency of tyrosine hydroxylase in the terminal of the nigrostriatal dopamine neuron, which is caused by GCH-1 deficiency. With an onset in childhood, stagnation of body length develops. For these symptoms, L-dopa demonstrates dramatic effects. In early-onset cases, tryptophan hydroxylase is also affected and patients show symptoms of serotonine deficiency. More than 100 mutations of the GCH-1 gene are detected; they are particular for each family. However, there is no particular mutation for postural and action type.