Department of Neurosciences, IRCCS Bambino Gesù Children Hospital, Rome, Italy; Department of System Medicine, University of Roma Tor Vergata, Rome, Italy.
Department of Neurosciences, IRCCS Bambino Gesù Children Hospital, Rome, Italy; University Hospital Pediatric Department, Bambino Gesù Children's Hospital, University of Rome Tor Vergata, Rome, Italy.
Parkinsonism Relat Disord. 2019 Apr;61:19-25. doi: 10.1016/j.parkreldis.2018.11.019. Epub 2018 Nov 16.
GNAO1 variants were recently discovered as causes of epileptic encephalopathies and heterogeneous syndromes presenting with movement disorders (MDs), whose phenomenology and clinical course are yet undefined. We herein focused on GNAO1-related MD, providing an analytical review of existing data to outline the main MD phenomenology and management, clinical evolution and genotype-phenotype correlations. Reviewing 41 previously published patients and assessing 5 novel cases, a comprehensive cohort of 46 patients was analyzed, reassuming knowledge about genotypes, phenotypes, disease course and treatment of this condition. GNAO1-related MD consisted of a severe early-onset hyperkinetic syndrome, with prominent chorea, dystonia and orofacial dyskinesia. Symptoms are poorly responsive to medical therapy and fluctuate, with critical and life-threatening exacerbations, such as status dystonicus. The presence of a choreiform MD appears to be predictive of a higher risk of movement disorder emergency. Surgical treatments are sometimes effective, although severe disabilities persist. Differently from the early infantile epileptic encephalopathy phenotype (associated with loss of function variants), no clear correlation between genotype and MD phenotype emerged, although some variants recurred more frequently, mainly affecting exons 6 and 7.
GNAO1 变异体最近被发现是癫痫性脑病和表现为运动障碍 (MD) 的异质性综合征的病因，其表型和临床过程尚未确定。我们在此重点关注与 GNAO1 相关的 MD，对现有数据进行分析性综述，以概述主要 MD 的表型和管理、临床演变和基因型-表型相关性。我们回顾了 41 例先前发表的患者，并评估了 5 例新病例，对 46 例患者进行了全面分析，重新评估了这种疾病的基因型、表型、病程和治疗的知识。GNAO1 相关的 MD 由严重的早发性多动综合征组成，表现为舞蹈症、肌张力障碍和口面运动障碍。症状对药物治疗反应不佳且波动，存在危及生命的恶化，如肌张力障碍状态。存在舞蹈 MD 似乎预示着运动障碍急症的风险更高。手术治疗有时有效，但严重残疾持续存在。与早发性婴儿癫痫性脑病表型（与功能丧失变异体相关）不同，基因型和 MD 表型之间似乎没有明确的相关性，尽管某些变异体更频繁地出现，主要影响外显子 6 和 7。
