目的:PHF21A与伴行为异常的智力发育障碍和伴或不伴癫痫发作的颅面畸形(IDDBCS)有关。这里,我们报告了一名新的IDDBCS患者,并回顾了以前报告的患者.
方法:我们回顾了新诊断患者和以前报道的IDDBCS患者的表型和遗传谱。
结果:在12例患者中(先前报告的病例为11例,我们在此报告的病例为患者),所有患者(100%)均有智力障碍(ID)和运动发育延迟.可获得认知信息的8例患者中有3例(37.5%)患有严重的ID;两名患者(25%)的ID为中度,三名患者的ID为轻度(37.5%)。12例患者中有7例(58.33%)出现癫痫表型,大多数(5/7,71.42%)受影响的个体发生了发育性和癫痫性脑病(DEE)。在5名DEE患者中,3人发展为婴儿癫痫性痉挛综合征(IESS)。2例患者(2/5,40%)的癫痫发作由抗癫痫药物控制。过度生长,多动症,低张力,ASD,100%观察到睡眠障碍,77.78%,70%,50%,33.33%的病人,分别。所有变体(100%)都是从头杂合变体。12例患者中有3例(25%)具有相同的变体(p。Arg580*)。最常见的变异类型是移码变异(7/12,58.33%),其次是无义变体(4/12,33.33%)和错义变体(1/12,8.33%)。IDDBCS的基因型-表型关系是不确定的,因为在具有相同变异的患者中观察到表型变异性(p。Arg580*)。我们在此报告的患者具有新的PHF21A基因变体(p。Gln97fs*20),导致神经发育迟缓,大头畸形,和IESS。
结论:IDDBCS的核心表型包括神经发育迟缓(智力障碍和运动技能受损),颅面异常,和过度生长。多动症,低张力,癫痫,ASD,睡眠障碍是IDDBCS的常见症状。值得注意的是,DEE是癫痫的显性表型,尤其是IESS。PHF21A可能是DEE的候选基因。从头变体是继承的主要模式。最常见的变体类型是移码变体,并且PHF21A中的变体p.Arg580*位于突变热点。
OBJECTIVE: 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.
METHODS: We reviewed the phenotypic and genetic spectrum of the newly diagnosed patient and previously reported patients with IDDBCS.
RESULTS: 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.
CONCLUSIONS: 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.