关键词: 　ATK3基因；　巨脑畸形；　发育迟缓；　儿童

Abstract: 　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.

Key words: ATK3 gene;　megalencephaly;　developmental delay;　child