A Canadian family of European descent with paroxysmal nonkinesigenic dyskinesia (PNKD), and a gene locus that links to a distinct region on chromosome 2q31, is reported by researchers at University of British Columbia, Canada. The age at onset in 10 affected members of the 14-member family was childhood in 2, teens in 2, and 30 to 50s in the remainder. They presented with episodes of dystonia, primarily affecting hands and feet symmetrically, and not triggered by movement, exercise, alcohol, caffeine or excitement. Attacks lasted 2-5 minutes and occurred daily. Treatment with various anticonvulsants, including acetazolamide, in one patient was ineffective. Mutation analysis of the MR-1 and GAD67 genes showed no linkage in affected family members. A genome-wide screen generated positive LOD scores at chromosome 2q31. [1]
COMMENT. This family is distinguished from 10 previously reported PNKD families in not having a linkage to the myofibrillogenesis regulator 1 gene (MR-1), on chromosome 2q32-36, but instead, having a novel gene locus at chromosome 2q31. Also, caffeine and alcohol, which act as consistent triggers in other PNKD pedigrees with MR-1 gene mutations, failed to stimulate attacks. Two different genes appear to be responsible for PNKD, indicative of genetic heterogeneity.