Frequency of the DYT1 mutation in primary torsion dystonia without family history

Background: Idiopathic torsion dystonia is a clinically and genetically het erogeneous movement disorder. A GAG deletion at position 946 of the DYT1 ge ne 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 rea ction and enzyme restriction analysis for the 946 GAG deletion, and genotyp e-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 a nd 12 years as in typical early-onset dystonia. All 4 patients had cranial muscle involvement, which is atypical for DYT1 mutation carriers. One had s egmental dystonia. Molecular analysis of relatives in 2 families demonstrat ed that the lack of family history was due to reduced penetrance. Conclusions: For accurate diagnosis and genetic counseling, screening for t he DYT1 deletion is of great interest in cases with generalized dystonia wi thout a family history. In other cases, positive results are rare.