Originally described as a risk factor for autism, CHD8 loss-of-function variants have recently been associated with a wider spectrum of neurodevelopmental abnormalities. We further expand the CHD8-related phenotype with the description of two unrelated patients who presented with childhood-onset progressive dystonia. Whole-exome sequencing conducted in two independent laboratories revealed a CHD8 nonsense variant in one patient and a frameshift variant in the second. The patients had strongly overlapping phenotypes characterized by generalized dystonia with mild-to-moderate neurodevelopmental comorbidity. Deep brain stimulation led to clinical improvement in both cases. We suggest that CHD8 should be added to the growing list of neurodevelopmental disorder-associated genes whose mutations can also result in dystonia-dominant phenotypes.

中文翻译：

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与 CHD8 致病性截断变异相关的儿童期进行性肌张力障碍

最初被描述为自闭症的危险因素，CHD8功能丧失变异最近与更广泛的神经发育异常有关。我们进一步扩展了与CHD8相关的表型，描述了两名患有儿童期发病的进行性肌张力障碍的无关患者。在两个独立实验室进行的全外显子组测序揭示了一名患者的CHD8无义变异和第二名患者的移码变异。这些患者具有强烈重叠的表型，其特征是全身性肌张力障碍伴轻度至中度神经发育合并症。在这两种情况下，深部脑刺激导致临床改善。我们建议CHD8应该被添加到不断增长的神经发育障碍相关基因列表中，这些基因的突变也可能导致肌张力障碍为主的表型。