Xiao-Jun Huang1, Tian Wang1, Jun-Ling Wang1, Xiao-Li Liu1, Xiang-Qian Che1, Jin Li1, Xiao Mao1, Mei Zhang1, Guang-Hui Bi1, Li Wu1, Yu Zhang1, Jing-Yi Wang1, Jun-Yi Shen1, Bei-Sha Tang2, Li Cao2, Sheng-Di Chen2. 1. From the Department of Neurology and Institute of Neurology (X.-J.H., T.W., X.-L.L., L.W., Y.Z., J.-Y.W., J.-Y.S., L.C., S.-D.C.), Rui Jin Hospital & Rui Jin Hospital North, Shanghai Jiao Tong University School of Medicine; Department of Neurology (J.-L.W., X.-Q.C., J.L., X.M., B.-S.T.), Xiangya Hospital, Central South University, Changsha, Hunan Province; Department of Neurology (M.Z.), Huainan First People's Hospital affiliated to Bengbu Medical College, Huainan, Anhui Province; and Department of Neurology (G.-H.B.), Dongying People's Hospital, Dongying, Shandong Province, China. 2. From the Department of Neurology and Institute of Neurology (X.-J.H., T.W., X.-L.L., L.W., Y.Z., J.-Y.W., J.-Y.S., L.C., S.-D.C.), Rui Jin Hospital & Rui Jin Hospital North, Shanghai Jiao Tong University School of Medicine; Department of Neurology (J.-L.W., X.-Q.C., J.L., X.M., B.-S.T.), Xiangya Hospital, Central South University, Changsha, Hunan Province; Department of Neurology (M.Z.), Huainan First People's Hospital affiliated to Bengbu Medical College, Huainan, Anhui Province; and Department of Neurology (G.-H.B.), Dongying People's Hospital, Dongying, Shandong Province, China. chen_sd@medmail.com.cn caoli2000@yeah.net bstang7398@163.com.
Abstract
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.
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.