Paroxysmal kinesigenic dyskinesia Clinical and genetic analyses of 110 patients

Objective:We aimed to investigate the clinical and genetic features of paroxysmal kinesigenic dyskinesia (PKD) in a large population and to analyze the genotype-phenotype correlation of PKD. Methods:We analyzed clinical manifestations and conducted PRRT2 screening in 110 patients with PKD. Clinical data were compared between 91 probands with and without PRRT2 mutations. Results:Among the enrolled participants (45 from 26 families, 65 sporadic cases), 8 PRRT2 mutations were detected in 20 PKD families (76.9%) and 14 sporadic cases (21.5%), accounting for 37.4% (34/91) of the study population. Five mutations (c.649dupC, c.649delC, c.487C>T, c.573dupT, c.796C>T) were already reported, while 3 mutations (c.787C>T, c.797G>A, c.931C>T) were undocumented. A patient harboring a homozygous c.931C>T mutation was shown to have inherited the mutation via uniparental disomy. Compared with non-PRRT2 mutation carriers, the PRRT2 mutation carriers were younger at onset, experienced longer attacks, and tended to present with complicated PKD, combined phenotypes of dystonia and chorea, and a positive family history. A good response was shown in 98.4% of the patients prescribed with carbamazepine. Conclusions:PRRT2 mutations are common in patients with PKD and are significantly associated with an earlier age at onset, longer duration of attacks, a complicated form of PKD, combined phenotypes of dystonia and chorea, and a tendency for a family history of PKD. A patient with uniparental disomy resulting in a homozygous c.931C>T mutation is identified in the present study. Carbamazepine is the first-choice drug for patients with PKD, but an individualized treatment regimen should be developed.