A decade ago, we described novel de novo submicroscopic deletions of chromosome 14q11.2 in three children with developmental delay, cognitive impairment, and similar dysmorphic features, including widely-spaced eyes, short nose with flat nasal bridge, long philtrum, prominent Cupid’s bow of the upper lip, full lower lip, and auricular anomalies. We suggested that this constituted a new multiple congenital anomaly—intellectual disability syndrome due to defects in CHD8 and/or SUPT16H. The three patients in our original cohort were between 2 years and 3 years of age at the time. Here we present a fourth patient and clinical updates on our previous patients. To document the longitudinal course more fully, we integrate published reports of other patients and describe genotype–phenotype correlations among them. Children with the disorder present with developmental delay, intellectual disability, and/or autism spectrum disorder in addition to characteristic facies. Gastrointestinal and sleep problems are notable. The identification of multiple patients with the same genetic defect and characteristic clinical phenotype, confirms our suggestion that this is a syndromic disorder caused by haploinsufficiency or heterozygous loss of function of CHD8.

十年前，我们描述了三个发育迟缓，认知障碍和类似畸形特征的儿童的从头新发现的14q11.2号染色体亚显微缺失，包括宽眼，鼻梁短，鼻梁扁平，长phil骨，丘比特突出上唇，下唇饱满和耳廓异常。我们建议这构成了一种新的多发性先天性异常-由于CHD8和/或SUPT16H的缺陷而导致的智力残疾综合征。我们最初队列中的三名患者当时在2岁至3岁之间。在这里，我们介绍了第四位患者以及先前患者的临床更新。为了更充分地记录纵向病程，我们整合了其他患者的已发表报告，并描述了他们之间的基因型与表型相关性。除特征相外，患有该疾病的儿童还会出现发育迟缓，智力障碍和/或自闭症谱系障碍。胃肠道和睡眠问题很明显。对具有相同遗传缺陷和特征性临床表型的多例患者的鉴定，证实了我们的建议，即这是由CHD8的单倍剂量不足或杂合性丧失引起的综合症。