CHD8 has been reported as an autism susceptibility/intellectual disability gene but emerging evidence suggests that it additionally causes an overgrowth phenotype. This study reports 27 unrelated patients with pathogenic or likely pathogenic CHD8 variants (25 null variants, two missense variants) and a male:female ratio of 21:6 (3.5:1, p < .01). All patients presented with intellectual disability, with 85% in the mild or moderate range, and 85% had a height and/or head circumference ≥2 standard deviations above the mean, meeting our clinical criteria for overgrowth. Behavioral problems were reported in the majority of patients (78%), with over half (56%) either formally diagnosed with an autistic spectrum disorder or described as having autistic traits. Additional clinical features included neonatal hypotonia (33%), and less frequently seizures, pes planus, scoliosis, fifth finger clinodactyly, umbilical hernia, and glabellar hemangioma (≤15% each). These results suggest that, in addition to its established link with autism and intellectual disability, CHD8 causes an overgrowth phenotype, and should be considered in the differential diagnosis of patients presenting with increased height and/or head circumference in association with intellectual disability.

中文翻译：

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CHD8 过度生长综合征：对 27 名患者出现的过度生长表型的详细评估。

CHD8 已被报道为自闭症易感性/智力残疾基因，但新出现的证据表明它还导致过度生长表型。本研究报告了 27 名不相关的患者患有致病性或可能致病性 CHD8 变异（25 个无效变异，2 个错义变异），男性：女性比例为 21:6 (3.5:1, p < .01)。所有患者都出现智力障碍，85% 处于轻度或中度范围，85% 的身高和/或头围高于平均值 ≥2 个标准差，符合我们的过度生长临床标准。大多数患者 (78%) 报告了行为问题，超过一半 (56%) 被正式诊断为患有自闭症谱系障碍或被描述为具有自闭症特征。其他临床特征包括新生儿肌张力减退 (33%) 和较少的癫痫发作，pes planus、脊柱侧弯、第五指弯曲、脐疝和眉间血管瘤（各≤15%）。这些结果表明，除了与自闭症和智力障碍建立联系外，CHD8 还会导致过度生长表型，在与智力障碍相关的身高和/或头围增加的患者的鉴别诊断中应予以考虑。