Chen Hui, Chen Yong, Wu Huaping, Qiu Xiaolu, Yu Xiongying, Wang Ruiyan, Zhong Jianmin, Peng Jing
Department of Neurology, Children's Hospital of Jiangxi Province, Nanchang, China.
Child healthcare department, Children's Hospital of Jiangxi Province, Nanchang, China.
Seizure. 2023 Oct;111:138-146. doi: 10.1016/j.seizure.2023.08.009. Epub 2023 Aug 18.
PHF21A has been associated with intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures (IDDBCS). Here, we report a new patient with IDDBCS and review previously reported patients.
We reviewed the phenotypic and genetic spectrum of the newly diagnosed patient and previously reported patients with IDDBCS.
Among 12 patients (11 whose cases were previously reported and the patient whose case we report here), all patients (100%) had intellectual disability (ID) and motor development delay. Three of 8 patients (37.5%) for whom information on cognition was available had severe ID; ID was moderate in two patients (25%) and mild in three patients (37.5%). Seven of the 12 patients (58.33%) had an epileptic phenotype, and the majority (5/7, 71.42%) of affected individuals developed developmental and epileptic encephalopathy (DEE). Of the 5 patients with DEE, three developed infantile epileptic spasm syndrome (IESS). The seizures of 2 patients (2/5, 40%) were controlled by antiseizure medications. Overgrowth, ADHD, hypotonia, ASD, and sleep disorders were observed in 100%, 77.78%, 70%, 50%, and 33.33% of patients, respectively. All of the variants (100%) were de novo heterozygous variants. Three of the 12 patients (25%) had the same variant (p.Arg580*). The most common types of variants were frameshift variants (7/12, 58.33%), followed by nonsense variants (4/12, 33.33%) and missense variants (1/12, 8.33%). Genotype-phenotype relationships for IDDBCS were uncertain, as phenotypic variability was observed among patients with the same variant (p.Arg580*). The patient whose case we report here had a novel PHF21A gene variant (p.Gln97fs*20), which caused neurodevelopmental delay, macrocephaly, and IESS.
The core phenotypes of IDDBCS include neurodevelopmental delay (intellectual disability and impaired motor skills), craniofacial abnormalities, and overgrowth. ADHD, hypotonia, epilepsy, ASD, and sleep disorders are common symptoms of IDDBCS. Notably, DEE is the dominant phenotype of epilepsy, especially IESS. PHF21A may be a candidate gene for DEE. De novo variants are the main mode of inheritance. The most common types of variants are frameshift variants, and the variant p.Arg580* in PHF21A is located at a mutation hot spot.
PHF21A与伴有行为异常和颅面畸形且有或无癫痫发作的智力发育障碍（IDDBCS）相关。在此，我们报告一名新的IDDBCS患者并回顾先前报道的患者。
我们回顾了新诊断患者以及先前报道的IDDBCS患者的表型和基因谱。
在12名患者（11名其病例先前已报道，1名是我们在此报告病例的患者）中，所有患者（100%）都有智力残疾（ID）和运动发育迟缓。在8名有认知信息的患者中，3名（37.5%）有严重ID；2名患者（25%）为中度ID，3名患者（37.5%）为轻度ID。12名患者中有7名（58.33%）有癫痫表型，且大多数（5/7，71.42%）受影响个体发生了发育性和癫痫性脑病（DEE）。在5名DEE患者中，3名发生了婴儿痉挛症（IESS）。2名患者（2/5，40%）的癫痫发作可通过抗癫痫药物控制。分别在100%、77.78%、70%、50%和33.33%的患者中观察到过度生长、注意力缺陷多动障碍（ADHD）、肌张力减退、自闭症谱系障碍（ASD）和睡眠障碍。所有变异（100%）均为新发杂合变异。12名患者中有3名（25%）有相同变异（p.Arg580*）。最常见的变异类型是移码变异（7/12，58.33%），其次是无义变异（4/12，33.33%）和错义变异（1/12，8.33%）。由于在具有相同变异（p.Arg580*）的患者中观察到表型变异性，因此IDDBCS的基因型 - 表型关系尚不确定。我们在此报告病例的患者有一个新的PHF21A基因变异（p.Gln97fs*20），其导致了神经发育迟缓、巨头畸形和IESS。
IDDBCS的核心表型包括神经发育迟缓（智力残疾和运动技能受损）、颅面异常和过度生长。ADHD、肌张力减退、癫痫、ASD和睡眠障碍是IDDBCS的常见症状。值得注意的是，DEE是癫痫的主要表型，尤其是IESS。PHF21A可能是DEE的候选基因。新发变异是主要的遗传方式。最常见的变异类型是移码变异，且PHF21A中的p.Arg580*变异位于一个突变热点。
