Division of Pediatric Neurology, Department of Pediatrics, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, Seoul, Korea.
Rare Disease Center, Seoul National University Hospital, Seoul, Korea.
Orphanet J Rare Dis. 2020 Dec 9;15(1):343. doi: 10.1186/s13023-020-01594-3.
GNAO1 encephalopathy is a rare neurodevelopmental disorder characterized by distinct movement presentations and early onset epileptic encephalopathy. Here, we report the in-depth phenotyping of genetically confirmed patients with GNAO1 encephalopathy, focusing on movement presentations.
Six patients who participated in Korean Undiagnosed Disease Program were diagnosed to have pathogenic or likely pathogenic variants in GNAO1 using whole exome sequencing. All medical records and personal video clips were analyzed with a literature review. Three of the 6 patients were male. Median follow-up duration was 41 months (range 7-78 months) and age at last examination was 7.4 years (range 3.3-16.9 years). Initial complaints were hypotonia or developmental delay in 5 and right-hand clumsiness in 1 patient, which were noticed at median age of 3 months (range 0-75 months). All patients showed global developmental delay and 4 had severely retarded development. Five patients (5/6, 83.3%) had many different movement symptoms with various onset and progression. The symptoms included stereotyped hands movement, non-epileptic myoclonus, dyskinesia, dystonia and choreoathetosis. Whole exome sequencing identified 6 different variants in GNAO1. Three were novel de novo variants and atypical presentation was noted in a patient. One variant turned out to be inherited from patient's mother who had mosaic variant. Distinct and characteristics movement phenotypes in patients with variant p.Glu246Lys and p.Arg209His were elucidated by in-depth phenotyping and literature review.
We reported 6 patients with GNAO1 encephalopathy showing an extremely diverse clinical spectrum on video. Some characteristic movement features identified by careful inspection may also provide important diagnostic insight and practice guidelines.
GNAO1 脑病是一种罕见的神经发育障碍，其特征为独特的运动表现和早期起病的癫痫性脑病。在此，我们报告了经基因证实的 GNAO1 脑病患者的深入表型分析，重点关注运动表现。
通过全外显子组测序，有 6 名参加韩国未确诊疾病计划的患者被诊断为 GNAO1 中存在致病性或可能致病性变异。对所有病历和个人视频片段进行了分析，并进行了文献复习。这 6 名患者中有 3 名是男性。中位随访时间为 41 个月（7-78 个月），最后一次检查时的年龄为 7.4 岁（3.3-16.9 岁）。5 名患者的初始症状为低张力或发育迟缓，1 名患者的右手笨拙，中位发病年龄为 3 个月（0-75 个月）。所有患者均表现为全面发育迟缓，4 例发育严重迟缓。5 名患者（5/6，83.3%）出现多种不同的运动症状，且发病和进展各异。这些症状包括刻板的手部运动、非癫痫性肌阵挛、运动障碍、肌张力障碍和舞蹈手足徐动症。全外显子组测序在 GNAO1 中发现了 6 种不同的变异。其中 3 种为新的从头变异，1 种患者的表现不典型。其中 1 种变异来自患者的母亲，其为镶嵌型变异。通过深入的表型分析和文献复习，阐明了携带变异 p.Glu246Lys 和 p.Arg209His 的患者的独特和特征性运动表型。
我们报告了 6 名 GNAO1 脑病患者的视频，他们表现出极其多样化的临床谱。通过仔细观察，一些特征性的运动特征也可能提供重要的诊断见解和实践指南。
