A childhood-onset rapid-onset dystonia Parkinsonism patient with ATP1A3 gene mutation and literature review

doi:10.3969/j.issn.1672-6731.2021.04.012

Abstract

Abstract:

Objective To study the clinical characteristics, diagnosis, treatment and prognosis of a patient with childhood-onset rapid-onset dystonia Parkinsonism (RDP) caused by ATP1A3 gene mutation, and review the related literature. Methods The patient with RDP caused by ATP1A3 gene mutation was admitted to Hunan Children's Hospital in March 2019. The clinical and genetic data of this patient had been analyzed retrospectively, and related literature from PubMed, Wanfang databases and CNKI to date (up to December 2019) with "Rapid-onset dystonia-parkinsonism", "RDP", "DYT12" as key words were reviewed. Results The patient was 4 years and 9 months (March 2019) old when she had the attack of the disease. After a febricity, she suddenly acquired acute aphasia, dysphagia, and movement disorder with a clear asthenic (face > arm > leg) gradient of involvement. Rehabilitation therapy and supportive treatment made his movement disorder gradually recovered but aphasia and dysphagia. Gene analysis showed that the ATP1A3 gene c. 2267G > A (p. R756H) site heterozygosity missense mutation existed in the patient. The mutation site was a pathogenic mutation of RDP, which had been reported in literature at home and abroad. The patient was treated with benzodiazepine and the effect was significant. At present, a total of 61 patients have been reported to date, and a total of 17 different mutations in ATP1A3 gene with RDP have been reported to date. The typical clinical phenotypes of RDP include the abrupt onset of dysarthria, dysphagia, limb dystonia with bradykinesia, among which bulbar paralysis was obvious and dystonia had an anatomical distribution clearly following a asthenic gradient (face > arm > leg). Conclusions The clinical characteristics of RDP are distinct, and ATP1A3 gene is its pathogenic gene. The analysis of the clinical characteristics and genetic characteristics of RDP will be conducive to the early diagnosis and treatment of RDP as well as the eugenics.

Key words: Dystonic disorders, Mutation, ATP1A3 gene (not in MeSH), Child

摘要：

目的总结1例ATP1A3基因突变所致儿童快发病性肌张力障碍-帕金森综合征（RDP）患儿的临床特点及诊疗经验。方法回顾分析1例RDP患儿临床资料，以“Rapid-onset dystonia parkinsonism”、“RDP”、“DYT12”及“快发病性肌张力障碍-帕金森综合征”等词组为关键词检索美国国立医学图书馆生物医学文献数据库（PubMed）、万方数据知识服务平台和中国知网中国知识基础设施工程（CNKI）等数据库相关文献并进行复习。结果患儿为4岁9个月女性，发热为首发症状，然后迅速出现失语、吞咽困难、竖头不稳、全身无力（无力症状面部 > 上肢 > 下肢），经营养神经、康复训练肢体无力症状逐渐改善，但仍遗留竖头不稳、构音及吞咽障碍。基因检测提示存在ATP1A3基因c.2267G > A（p.R756H）位点杂合错义突变，苯二氮类药物治疗后病情明显缓解。截至2019年12月，全球共报道61例RDP病例、17个致病性ATP1A3基因突变位点；典型表现为发病急骤、特征性头腿梯度差性肌张力障碍、构音障碍、吞咽困难、姿势不稳、运动迟缓，以及明显的延髓麻痹症状。结论 RDP由致病性ATP1A3基因突变所致，临床特征鲜明，苯二氮类药物治疗反应良好。提高对RDP临床特征及遗传学特点的认识，有利于早期诊断、及时治疗和优生优育。

关键词: 张力障碍, 突变, ATP1A3基因(非MeSH词), 儿童

KANG Qing-yun, LIAO Cai-shi, LIAO Hong-mei, CHEN Bo, YANG Li-ming. A childhood-onset rapid-onset dystonia Parkinsonism patient with ATP1A3 gene mutation and literature review[J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2021, 21(4): 304-309.

康庆云, 廖彩时, 廖红梅, 陈波, 杨理明. ATP1A3基因突变致儿童快发病性肌张力障碍-帕金森综合征一例并文献复习[J]. 中国现代神经疾病杂志, 2021, 21(4): 304-309.

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