目的 探讨MEHMO综合征的临床特征与遗传学特点。方法 回顾分析2例确诊MEHMO综合征患儿的临床资料，并 复习相关文献。结果 两例患儿均为男性。例1于2岁3个月就诊，表现为癫痫发作、智力低下、进行性痉挛性四肢瘫、小头畸形、 面部畸形、身材矮小和隐睾等。例2于3月龄就诊，4个月15天龄死亡，表现为反复低血糖、小头畸形和小阴茎，癫痫状态持续、难 治。两例患儿均存在乳酸酸中毒，头颅MRI均显示胼胝体薄。例1患儿EIF 2 S 3基因存在c.137C>T（p.Thr46Ile）错义变异，例2患儿 EIF 2 S 3基因存在c.1391_c.1394delCAAT（p.T464Tfs*5）移码变异。这2种变异在人类基因变异数据库（HGMD）等均未见收录，美 国医学遗传学与基因组学（ACMG）基因变异解读指南均评定为致病性变异。检索到国外文献5篇，包含18例患者，有5个EIF2S3基 因变异位点，1个移码变异和4个错义变异，均为半合子变异。移码变异患者表现出智力障碍、癫痫发作、生殖器发育不全、小头畸形、 肥胖、发育迟缓和低血糖等MEHMO综合征的全部重要表型，而错义变异患者表现部分表型且症状较轻。结论 MEHMO综合征存 在一定的基因型-表型相关性。首次报道2例中国人群MEHMO综合征，并发现2个新的EIF 2 S 3基因变异位点。

Objective To explore the clinical and genetic characteristics of MEHMO syndrome. Methods The clinical data of MEHMO syndrome in 2 children were analyzed retrospectively, and the related literatures were reviewed. Results Both cases were male. Case 1 was admitted at 2 years and 3 months of age. He presented with epileptic seizure, mental retardation, progressive spastic tetraplegia, microcephaly, facial deformity, short stature, and cryptorchidism. Case 2 visited at the age of 3 months and died at the age of 4 months and 15 days. The child presented with recurrent hypoglycemia, microcephaly, small penis, persistent and refractory epilepsy. Both cases had lactic acidosis, and MRI showed thin corpus callosum. There was a missense mutation of c.137 C>T (p.Thr46 Ile) in EIF 2 S 3 gene in case 1 , and a frameshift mutation of c.1391 _c.1394 delCAAT (p.T464 Tfs* 5 ) in EIF 2 S 3 gene in case 2 . These two mutations have not been included in the human genetic variation database (HGMD), and both were classified as pathogenic by American College of Medical Genetics and Genomics (ACMG) classification. Five foreign literatures were retrieved, including 18 patients. There were five EIF 2 S 3 gene mutation sites, one frameshift mutation and four missense mutations, all of which were hemizygous mutations. Patients with frameshift mutation showed all important phenotypes of MEHMO syndrome, such as mental retardation, epilepsy, genital dysplasia, microcephaly, obesity, stunting and hypoglycemia, while patients with missense mutation showed parts of phenotypes and mild symptoms. Conclusion There is a certain genotype-phenotype correlation in MEHMO syndrome. Two cases of MEHMO syndrome in Chinese population were reported for the first time, and two new mutation sites of EIF 2 S 3 gene were found.