Xiaoli Liu1, Huiyi Ke2,3, Xiaohang Qian4, Shige Wang4, Feixia Zhan2, Ziyi Li2,3, Wotu Tian2, Xiaojun Huang4, Bin Zhang5, Li Cao6. 1. Department of Neurology, Shanghai Fengxian District Central Hospital, Shanghai Jiao Tong University Affiliated Sixth People's Hospital South Campus, Shanghai, 201406, China. 2. Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yi Shan Road, Shanghai, 200233, China. 3. Department of Clinical Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. 4. Department of Neurology and Institute of Neurology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. 5. Department of Neurology, Shanghai Fengxian District Central Hospital, Shanghai Jiao Tong University Affiliated Sixth People's Hospital South Campus, Shanghai, 201406, China. zhangbin0807@126.com. 6. Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yi Shan Road, Shanghai, 200233, China. caoli2000@yeah.net.
Abstract
BACKGROUND: Mutations in PRRT2 and 16p11.2 microdeletion including PRRT2 have been identified as the pathogenic cause of paroxysmal kinesigenic dyskinesia (PKD). OBJECTIVE: The objective was to investigate the clinical and genetic features of PKD and to analyze the genotype-phenotype correlation. METHODS: We recruited PKD patients, recorded clinical manifestations, and performed PRRT2 screening in 150 PKD patients by unified PKD registration forms. Genotype-phenotype correlation analyses were conducted in probands. High-knee-exercise (HKE) tests were applied in one hundred and six patients. RESULTS: Eight PRRT2 mutations were detected, accounting for 22.76% of the probands. Three mutations (c.649dupC, c.649delC, and c.510_513delTCTG) were already reported, while four mutations (c.252_264delCACAGACCTCAGC, c.503_504delCT, c.679C > T, and c.804C > A) were first reported. One heterozygous microdeletion of 606 kb in 16p11.2 was detected in one patient. 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. 57.01% of patients could effectively induce movement disorders through the HKE test. A good response was shown in 81.93% of the patients prescribed with antiepileptic drugs. 13.54% (13/96) had abnormal EEG results. 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. Patients with microdeletion of 16p11.2 may have more severe manifestations. The HKE test could contribute to the diagnosis of PKD. Carbamazepine is still the first choice for PKD patients, but individualized treatment should be formulated.
BACKGROUND: Mutations in PRRT2 and 16p11.2 microdeletion including PRRT2 have been identified as the pathogenic cause of paroxysmal kinesigenic dyskinesia (PKD). OBJECTIVE: The objective was to investigate the clinical and genetic features of PKD and to analyze the genotype-phenotype correlation. METHODS: We recruited PKD patients, recorded clinical manifestations, and performed PRRT2 screening in 150 PKD patients by unified PKD registration forms. Genotype-phenotype correlation analyses were conducted in probands. High-knee-exercise (HKE) tests were applied in one hundred and six patients. RESULTS: Eight PRRT2 mutations were detected, accounting for 22.76% of the probands. Three mutations (c.649dupC, c.649delC, and c.510_513delTCTG) were already reported, while four mutations (c.252_264delCACAGACCTCAGC, c.503_504delCT, c.679C > T, and c.804C > A) were first reported. One heterozygous microdeletion of 606 kb in 16p11.2 was detected in one patient. 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. 57.01% of patients could effectively induce movement disorders through the HKE test. A good response was shown in 81.93% of the patients prescribed with antiepileptic drugs. 13.54% (13/96) had abnormal EEG results. 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. Patients with microdeletion of 16p11.2 may have more severe manifestations. The HKE test could contribute to the diagnosis of PKD. Carbamazepine is still the first choice for PKD patients, but individualized treatment should be formulated.
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