[A case of intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures caused by PHF21A gene variation and review of literature].

Objective: To discuss the clinical and genetic features of intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures (IDDBCS). Methods: The clinical and genetic records of a patient who was diagnosed with IDDBCS caused by PHF21A gene variation at Children's Hospital Capital Institute of Pediatrics in 2021 were collected retrospectively. Using " PHF21A gene" as the keyword, relevant articles were searched at CNKI, Wanfang Data and PubMed from establishment of databases to February 2023. Clinical and genetic features of IDDBCS were summarized in the combination of this case. Results: An 8 months of age boy showed overgrowth (height, weight and head circumference were all higher than the 97th percentile of children of the same age and sex) and language and motor developmental delay after birth, and gradually showed autism-like symptoms like stereotyped behavior and poor eye contact. At 8 months of age, he began to show epileptic seizures, which were in the form of a series of spastic seizures with no reaction to adrenocorticotropic hormone but a good response to vigabatrin. Physical examination showed special craniofacial appearances including a prominent high forehead, sparse eyebrows, broad nasal bridge, and downturned mouth with a tent-shaped upper lip. The patient also manifested hypotonia. Whole exome sequencing showed a de novo heterogeneous variant, PHF21A (NM_001101802.1): c.54+1G>A, and IDDBCS was diagnosed. A total of 6 articles (all English articles) were collected, involving this case and other 14 patients of IDDBCS caused by PHF21A gene variation. Clinical manifestations were intellectual disability or developmental delay (15 patients), craniofacial anomalies (15 patients), behavioral abnormalities (12 patients), seizures (9 patients), and overgrowth (8 patients). The main pathogenic variations were frameshift variations (8 patients). Conclusions: IDDBCS should be considered when patients show nervous developmental abnormalities, craniofacial anomalies, seizures and overgrowth. PHF21A gene variation detection helps to make a definite diagnosis.目的： 探讨PHF21A基因相关智力发育障碍、行为异常并颅面畸形伴或不伴癫痫发作（IDDBCS）的临床和遗传学特点。 方法： 回顾性分析2021年首都儿科研究所附属儿童医院诊治的1例PHF21A基因相关IDDBCS患儿的临床资料和遗传学检测结果，以“PHF21A基因”或“PHF21A gene”为检索词分别查阅中国知网、万方及PubMed数据库建库至2023年2月的相关文献，结合本例资料总结IDDBCS的临床和遗传学特征。 结果： 患儿，男，8月龄，自幼即出现身材过度生长（身长、体重及头围均大于同龄同性别儿童P97）及语言、运动发育落后，并渐出现刻板行为、眼神交流不良等孤独症谱系障碍样表现。8月龄出现痉挛发作，成簇出现，促肾上腺皮质激素治疗无效，氨己烯酸效果良好。体格检查示特殊面容（额头突出、眉毛稀疏、鼻梁宽、口角下垂、上唇呈帐篷状），肌张力低下。全外显子二代测序分析示PHF21A基因（NM_001101802.1）新生杂合变异：c.54+1G>A，确诊为IDDBCS。检索到PHF21A基因相关IDDBCS文献6篇（均为英文），包括本例患儿共15例患者，主要临床表现为智力障碍或发育迟缓（15例）、颅面畸形（15例）、行为异常（12例）、癫痫（9例）、过度生长（8例），致病性变异以移码变异为主（8例）。 结论： 当患儿存在神经发育异常、颅面畸形、癫痫和过度生长时，需考虑IDDBCS，基因检测发现PHF21A基因变异可明确诊断。.