The Genetic Landscape of Complex Childhood-Onset Hyperkinetic Movement Disorders.
The Genetic Landscape of Complex Childhood-Onset Hyperkinetic Movement Disorders.
复制标题
DOI：
10.1002/mds.29182
复制
发表时间：
2022-11
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
这项研究的目的是更好地描述复杂的、早发性的、单基因多动症的遗传图景和关键的临床特征。患者来自14个国际中心。参与研究的临床医生完成了标准化的形式表格，获取了人口统计学、临床和遗传学数据。两位儿科运动障碍专家审查了可用的视频片段，根据公布的标准对多动症进行分类。共检测到140例17个不同基因(ADCY5、ATP1A3、DDC、DHPR、FOXG1、GCH1、GNAO1、KMT2B、MICU1、Nkx2.1、PDE10A、PTPs、SGCE、SLC2A1、SLC6A3、SPR和TH)的致病变异患者。在大多数患者中，多动症运动是全面性的(77%)，大多数患者(69%)表现出合并的运动符号。帕金森病-肌张力障碍是原发性神经递质疾病(DDC、DHPR、PTPS、SLC6A3、SPR、TH)的特征；舞蹈症在ADCY5-、ATP1A3-、FOXG1-、Nkx2.1-、SLC2A1-、GNAO1-和PDE10A相关疾病中占主导地位；刻板印象是FOXG1和GNAO1相关疾病的显著特征。有全身性运动亢进的患者起病早于局灶性/节段性运动者(2.5 ± 0.3比4.7 ± 0.7 年；P=0.0.007)。发育迟缓者也较神经发育正常者更早出现多动运动(1.5 ± 2.9vs.4.7 ± 3.8 ；P <； 0.001)。有效的针对疾病的治疗包括针对神经递质紊乱的多巴胺能药，针对葡萄糖转运体缺乏症的生酮饮食，以及针对SGCE、KMT2B和GNAO1相关的运动亢进的脑深部刺激。这项研究强调了在遗传性多动运动障碍儿童中观察到的复杂表型，这可能导致诊断困难。我们提供了一个全面的运动符号学分析，以指导医生在这些患者的基因调查，以促进早期诊断，精确的药物治疗，和遗传咨询。©2022作者。《运动障碍》由Wiley期刊有限责任公司代表国际帕金森病和运动障碍协会出版
The objective of this study was to better delineate the genetic landscape and key clinical characteristics of complex, early‐onset, monogenic hyperkinetic movement disorders. Patients were recruited from 14 international centers. Participating clinicians completed standardized proformas capturing demographic, clinical, and genetic data. Two pediatric movement disorder experts reviewed available video footage, classifying hyperkinetic movements according to published criteria. One hundred forty patients with pathogenic variants in 17 different genes (ADCY5, ATP1A3, DDC, DHPR, FOXG1, GCH1, GNAO1, KMT2B, MICU1, NKX2.1, PDE10A, PTPS, SGCE, SLC2A1, SLC6A3, SPR, and TH) were identified. In the majority, hyperkinetic movements were generalized (77%), with most patients (69%) manifesting combined motor semiologies. Parkinsonism‐dystonia was characteristic of primary neurotransmitter disorders (DDC, DHPR, PTPS, SLC6A3, SPR, TH); chorea predominated in ADCY5‐, ATP1A3‐, FOXG1‐, NKX2.1‐, SLC2A1‐, GNAO1‐, and PDE10A‐related disorders; and stereotypies were a prominent feature in FOXG1‐ and GNAO1‐related disease. Those with generalized hyperkinetic movements had an earlier disease onset than those with focal/segmental distribution (2.5 ± 0.3 vs. 4.7 ± 0.7 years; P = 0.007). Patients with developmental delay also presented with hyperkinetic movements earlier than those with normal neurodevelopment (1.5 ± 2.9 vs. 4.7 ± 3.8 years; P < 0.001). Effective disease‐specific therapies included dopaminergic agents for neurotransmitters disorders, ketogenic diet for glucose transporter deficiency, and deep brain stimulation for SGCE‐, KMT2B‐, and GNAO1‐related hyperkinesia. This study highlights the complex phenotypes observed in children with genetic hyperkinetic movement disorders that can lead to diagnostic difficulty. We provide a comprehensive analysis of motor semiology to guide physicians in the genetic investigation of these patients, to facilitate early diagnosis, precision medicine treatments, and genetic counseling. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
登录
查看更多内容
影响因子：
5.1
作者：
Gatto, Emilia M.;Walker, Ruth H.;Jinnah, Hyder A.
通讯作者：
Jinnah, Hyder A.
影响因子：
9.9
作者：
Leuzzi, V;Carducci, C;Antonozzi, I
通讯作者：
Antonozzi, I
影响因子：
9.9
作者：
Papandreou A;Schneider RB;Augustine EF;Ng J;Mankad K;Meyer E;McTague A;Ngoh A;Hemingway C;Robinson R;Varadkar SM;Kinali M;Salpietro V;O'Driscoll MC;Basheer SN;Webster RI;Mohammad SS;Pula S;McGowan M;Trump N;Jenkins L;Elmslie F;Scott RH;Hurst JA;Perez-Duenas B;Paciorkowski AR;Kurian MA
通讯作者：
Kurian MA
影响因子：
36.4
作者：
Chien, Yin-Hsiu;Lee, Ni-Chung;Hwu, Wuh-Liang
通讯作者：
Hwu, Wuh-Liang
DOI：
10.1111/j.1469-8749.2012.04287.x
发表时间：
2012-07-01
影响因子：
3.8
作者：
Dale, Russell C.;Grattan-Smith, Padraic;Peters, Greg B.
通讯作者：
Peters, Greg B.