AKT3基因相关巨脑畸形1例报告并文献复习

AKT 3-related megalencephaly:a case report and literature review

目的探讨AKT3基因相关巨脑畸形(MEG)的临床特征。方法回顾分析1例AKT3基因相关MEG患儿的临床资料,并复习相关文献。结果女性患儿,4月龄,出生时无异常,出生胎龄39+4周,体质量3120 g,头围37 cm。出生后头围随月龄进行性增大,前额、后枕部突出,发育迟缓,四肢肌张力偏低,脊柱、四肢未见畸形。Gesell发育量表评估总发育商69。血生化、串联质谱、尿有机酸检查未见异常。头颅磁共振成像示双侧大脑半球脑白质量偏少,皮层信号相对未见异常,双侧侧脑室稍扩大。脑部血管成像未见明显异常。脑电图示正常婴儿脑电图。染色体核型分析未见异常。全外显子测序检测发现患儿AKT3基因存在c.1393C>T(p.Arg465Trp)杂合变异。根据美国ACMG变异分类指南,考虑该变异为"2类-可能致病",提示患儿存在AKT3基因相关MEG。查阅文献,上述变异已在国外多个MEG患者中被报道过,国内尚未见报道。结论MEG主要特征为头围增大,伴不同程度发育迟缓,可伴癫痫发作、孤独症等,部分存在多小脑回畸形、局灶性皮层发育不良,其临床表型谱复杂,基因测序有助于明确诊断。

Objective To investigate the clinical features of AKT3-related megalencephaly(MEG).Methods The patient’s clinical manifestations,laboratory examination and genetic analysis were analyzed retrospectively and related literatures were reviewed.Results A 4-month-old girl with large head size and developmental delay was reported.This female patient was 39+4 weeks of gestational age with birth weight of 3120 g and no asphyxia at birth.The clinical features included progressive enlargement of head size with age,prominent forehead and occiput,developmental delay and mild hypotonia.Gesell development scale demonstrated mild global developmental delay with a full scale score of 69.Brain MRI showed mild ventriculomegaly and loss of bilateral white matter with no abnormalities of cortical signals.Brain MRA and EEG were normal.No abnormalities were shown in biochemistry metabolism tests and chromosome karyotype analysis.Whole exome sequencing revealed a de novo missense mutation c.1393C>T(p.Arg465Trp)in AKT3 gene.According to ACMG,the mutation was"2-Likely pathogenic".Therefore,the girl was diagnosed with AKT3 related MEG.Though several cases with this mutation were reported abroad,there was no relevant report in domestic after reviewing the literatures.Conclusions The main clinical features of AKT3 related MEG include progressive enlargement of head size,various range of developmental delay,some with epilepsy and autism,and some with polymicrogyria or focal cortical dysplasia.The clinical spectrum of this disease is very broad.And gene sequencing can help the diagnosis of this disease.