Frequency of the DYT1 Mutation in Primary Torsion Dystonia Without Family History

Background Idiopathic torsion dystonia is a clinically and genetically heterogeneous movement disorder. A GAG deletion at position 946 of the DYT1 gene was the first mutation found, in early-onset dystonia, with an autosomal dominant transmission and reduced penetrance. Objective To evaluate the frequency of the DYT1 mutation in patients with idiopathic torsion dystonia but without a family history. Design Prospective cohort study. Setting Four botulinum toxin clinics in the Paris, France, area. Patients A French population of 100 patients with dystonia. Main Outcome Frequency of the DYT1 mutation tested by polymerase chain reaction and enzyme restriction analysis for the 946 GAG deletion, and genotype-to-phenotype correlation. Results Only 5 mutation carriers were identified, 4 of whom were part of a group of 10 patients with generalized dystonia. Onset was between ages 5 and 12 years as in typical early-onset dystonia. All 4 patients had cranial muscle involvement, which is atypical for DYT1 mutation carriers. One had segmental dystonia. Molecular analysis of relatives in 2 families demonstrated that the lack of family history was due to reduced penetrance. Conclusions For accurate diagnosis and genetic counseling, screening for the DYT1 deletion is of great interest in cases with generalized dystonia without a family history. In other cases, positive results are rare.