41例46,XY性别发育异常临床诊治及基因筛查结果分析

Clinical analysis and genetic screening of 41 children with 46, XY DSD

目的探讨儿童46,XY性别发育异常的诊疗策略,并总结其诊疗经验。方法回顾性分析41例2011年9月至2018年11月于中国医科大学附属盛京医院确诊为46,XYDSD患儿的临床表现、实验室及影像学检查结果、基因检测结果和病理结果等资料,并总结其临床特征。结果41例中社会性别男28例(68.3%),女13例(31.7%),初诊年龄3个月至15岁。外生殖器完全女性化3例,外生殖器明显男性化17例,外生殖器模糊21例。染色体检查结果均为46,XY,且SRY基因阳性。35例行HCG激发试验,23例行性别发育相关基因筛查,8例行组织学检查。其中性腺发育异常17例,雄激素合成或作用缺陷16例,苗勒氏管永存综合征6例,Kallmann综合征2例。6例接受性腺切除术,10例接受外生殖器整形术,11例接受睾丸固定术,2例接受性别重新认定,10例未进行性别选择,其余29例维持原来社会性别。结论46,XYDSD患儿临床表现个体间差异较大,除性腺发育异常及睾丸消失综合征外,其余患儿最终需要结合基因检测结果以明确诊断。性别选择是46,XYDSD治疗的关键,需要全面评估后进行慎重选择。对于睾丸功能良好的患儿,最好让患儿自己参与性别的选择,尽量避免不可逆的性腺切除及外生殖器手术。

Objective To explore the clinical presentations,diagnosis and therapy for 46,XY disorders of development(DSD).Methods A retrospective study was performed for 41 hospitalized 46,XY DSD patients from September 2011 to November 2018.Their clinical data were analyzed.And the relevant genes were sequenced for detecting gene mutations.Results Among them,the dominant social gender was male(n=28,68.3%)and female(n=13,31.7%).The initial diagnostic age was from 3 months to 15 years.Three major categories of external genitalias were ambiguous(n=21),male(n=17)and female(n=3).In 8 patients,open or laparoscopic exploration was performed with gonadal biopsy for histological evaluations.In another 35 patients,human chorionic gonadotropin(HCG)stimulation test was performed for assessing testicular functions.Gene analyses were performed in 23 patients.There were gonadal dysgenesis(n=17),disorders of androgen synthesis plus androgen insensitivity syndrome(n=16),persistent müllerian duct syndrome(n=6)and Kallmann syndrome(n=2).The procedures included gonadectomy(n=6),external genital plastic surgery(n=10)and orchiopexy(n=11).After operation,the outcomes were reassigned gender of rearing(n=2),sex non-selection(n=10)and original gender(n=29).Conclusion Heterogeneity exists in clinical phenotypes of children diagnosed as 46,XY DSD.Genetic testing is required for a definite diagnosis of this disease,except for children with gonadal dysgenesis and vanishing testes syndrome.Gender assignment is crucial in the treatment of 46,XY DSD.It is necessary to choose carefully after comprehensive evaluations.For those without remarkable disorder of testis function,it is wiser to let the child participate in sex selection and avoid irreversible gonadectomy and genital surgery.