Clinical and genetic analyses of 150 patients with paroxysmal kinesigenic dyskinesia
Clinical and genetic analyses of 150 patients with paroxysmal kinesigenic dyskinesia
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150例阵发性运动源性运动障碍患者的临床及遗传学分析
DOI：
10.1007/s00415-022-11103-0
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发表时间：
2022-04-15
影响因子：
6
通讯作者：
Cao, Li
中科院分区：
文献类型：
--
作者：
Liu, Xiaoli;Ke, Huiyi;Cao, Li
背景PRRT 2突变和包括PRRT 2在内的16 p11.2微缺失已被确定为阵发性运动诱发性运动障碍（PKD）的致病原因。目的探讨PKD的临床和遗传学特征，分析基因型与表型的相关性。方法招募PKD患者，记录临床表现，并使用统一的PKD登记表对150例PKD患者进行PRRT 2筛查。先证者进行基因型-表型相关分析。对106例患者进行了高膝运动（HKE）试验。结果共检测到8个PRRT 2突变，占先证者的22.76%。已经报道了三个突变（c.649dupC、c.649delC和c.510_513delTCTG），而四个突变（c.252_264delCACAGACCTCAGC、c.503_504delCT、c.679C > T和c.804C > A）是首次报道的。在1例患者中检测到16p11.2的606 kb杂合微缺失。与非PRRT 2突变携带者相比，PRRT 2突变携带者发病年龄更小，发作时间更长，倾向于表现为复杂的PKD，肌张力障碍和舞蹈病的联合表型。57.01%的患者能通过HKE试验有效诱发运动障碍。81.93%的患者服用抗癫痫药物后有良好反应。13.54%（13/96）脑电图异常。结论PRRT 2基因突变在PKD患者中较为常见，且与PKD发病年龄早、病程长、病情复杂、肌张力障碍和舞蹈病的合并表型密切相关。16p11.2微缺失的患者可能有更严重的表现。HKE试验有助于PKD的诊断。卡马西平仍是PKD患者的首选药物，但应制定个体化治疗方案。
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.