Secondary dystonia and the DYTI gene

Early-onset (< 28 years) primary dystonia in most Ashkenazi Jews is due to a single founder mutation in the DYT1 gene on chromosome 9q34, as determined by very strong linkage disequilibrium with a haplotype of 9q34 alleles at surrounding marker loci. The role of this mutation in individuals with secondary causes for dystonia has never been tested, although environmental insults, such as neuroleptic exposure or perinatal asphyxia, are proposed to precipitate dystonia in genetically predisposed individuals. We assessed 9q34 haplotypes in 40 Ashkenazi patients with secondary dystonia; 25 had early onset of symptoms, including 15 with exposure to neuroleptic medication or perinatal asphyxia. Of the 25 patients with early onset, 9 were considered phenocopies of DYT1 having normal examinations except for dystonia, normal radiographic and other laboratory studies, and onset in a limb or the neck. Only one individual whose dystonia developed in the setting of a measles infection carried the associated haplotype. Our findings indicate that clinical diagnostic criteria that include historical information to detect tardive dystonia and perinatal asphyxia discriminate primary dystonia due to the DYT1 founder mutation. We found no evidence that the DYT1 founder mutation contributes to secondary dystonia.