Sotos综合征患儿临床特征及基因变异分析

Analysis of clinical features and genetic variation of Sotos syndrome

目的分析1例误诊为性早熟的Sotos综合征患儿的临床特征及基因变异特点。方法回顾性分析1例误诊为性早熟的Sotos综合征患儿的临床资料及相关实验室检查结果。结果患儿临床表现为生长过快、发育落后、特殊面容(大头颅、前额突出、下颌窄、高腭弓)。外院误诊为性早熟,给予醋酸曲普瑞林治疗15个月,生长速度未见减缓。基因测序显示患儿核受体结合SET域蛋白1(NSD1)基因(NM_022455.4)存在“错义变异c.5854C>T(p.Arg1952Trp)(杂合)”,其父亲携带该位点变异(杂合)。按照美国医学遗传学和基因组学学会(ACMG)变异分类标准,归类为“可能致病性变异”。结论该患儿确诊为Sotos综合征,NSD1基因突变是其致病原因。Sotos综合征以身高增长过快为主要表现,伴随骨龄显著提前,不能仅靠性激素激发试验结果与性早熟鉴别,临床应严格评估第二性征发育,避免误诊。

Objective To analyze clinical characteristics and genetic variation of a case of Sotos syndrome misdiagnosed as precocious puberty.Methods The clinical data and related laboratory test results from one child with Sotos syndrome misdiagnosed as precocious puberty were retrospectively analyzed.Results Clinical manifestations of the child presented overgrowth,developmental delay,and typical facial appearance(macrocephaly,broad forehead,pointed chin,high palate).The patient was misdiagnosed as precocious puberty in other hospital and treated with triptorelin acetate for 15 months,but growth rate has not slowed down.Heterozygous missense variants in nuclear receptor-binding SET-domain-containing protein 1(NSD1)gene was identified in proband by gene sequencing,which was c.5854C>T(p.Arg1952Trp).His father had the same heterozygous mutation.This mutation had been classified to likely pathogenic mutation by American College of Medical Genetics and Genomics(ACMG)variation classification criteria.Conclusion The diagnosis of Sotos syndrome is confirmed in this child and NSD1 gene mutation is the cause.Sotos syndrome is characterized by overgrowth and bone age advanced.The results of the provocation test cannot be distinguished from precocious puberty alone.The clinical development of secondary sexual characteristics should be strictly evaluated to avoid misdiagnosis.