Familial paroxysmal dystonic choreoathetosis - Clinical findings in a large Japanese family and genetic linkage to 2q

Background: Paroxysmal dystonic choreoathetosis (PDC) is a rare familial mo vement disorder that has been mapped to chromosome 2q31-36. Objective: To study the first Japanese family with PDC clinically and genet ically. Patients and Methods: We studied a large Japanese family in which at least 17 members in 6 generations have been affected by PDC. We interviewed and e xamined 26 family members, 8 of whom revealed choreoathetosis-like and dyst onialike involuntary movement and 1 of whom revealed no involuntary movemen t but only muscle stiffness such as the aura of paroxysmal dystonic choreoa thetosis (PDC). Genetic linkage studies of this family were carried out wit h polymorphic DNA markers. Results: The attacks of involuntary movement or muscle stiffness were preci pitated by ovulation, menstruation, emotional stress, or caffeine or alcoho l ingestion. Magnetic resonance imaging of the brain revealed no abnormalit ies. Clonazepam therapy was effective for reducing the attacks, and ingesti on of garlic was believed by patients to be effective for softening the att acks. An affected woman with only muscle stiffness showed remission after h ysterectomy for hysteromyoma. This woman also had the disease haplotype and transferred it to her typical PDC-affected daughter. Maximal pairwise loga rithm of odds scores exceeding 2.00 were obtained at D2S2250, D2S1242, D2S3 77, D2S2148, and D2S126. The PDC gene was demonstrated by linkage analyses to be located in a 15.3-centimorgan interval lying between D2S371 and D2S33 9 based on pairwise and multipoint logarithm of odds scores and obligate re combination events in affected individuals. Conclusions: Linkage of PDC to chromosome 2q32-36 was confirmed in a Japane se family. The clinical characterizations of this family with PDC include t hat ovulation seems also to be a precipitating factor of the attacks and th at hysterectomy seems to be effective for softening the attacks. Although l ow-dose clonazepam treatment was most effective, garlic use was believed by affected members to be effective for softening the attacks. Furthermore, b ased on the results of clinical and genetic analyses, we suggest that muscl e stiffness without involuntary movement may represent a forme fruste of PD C.