混合性性腺发育不良的临床特点与误诊分析

目的探讨混合性性腺发育不良(mixed gonadal dysgenesis,MGD)患儿的临床特点、导致误诊的原因及处理方式。方法回顾性分析2013年5月至2018年4月收治的24例MGD患儿的临床资料。24例患儿的年龄在10~39个月,平均21个月;身高71~97 cm,平均83 cm,其中10例患儿身高低于同年龄段平均身高2个标准差;就诊时22例抚养性别为男,2例抚养性别为女。Prader分级Ⅱ级3例,Ⅲ级15例,Ⅳ级6例。分析患儿性激素测定、性发育相关基因检测结果。对8例常规核型分析性染色体为46,XY的患儿采用荧光原位杂交(fluorescence in situ hybridization,FISH)方法复测,光学显微镜观察患儿切除或活检的性腺组织。结果本组患儿AMH值在16.57~189.92 ng/ml,均值为69.42 ng/ml;hCG刺激实验后睾酮值在0.71~8.09 nmol/L,均值为4.93 nmol/L。基因检测发现WT1基因致病突变,合并低蛋白血症和蛋白尿1例,诊断为Denys-Drash综合征。核型分析示,12例核型为45,X/46,XY,10例为46,XY(其中8例完成FISH检查证实性染色体为X嵌合XY),1例为45,X/46,XY/47,XYY,1例为45,X/47,XYY/48,XYYY。24例均存在阴道,22例探查到子宫或半角子宫。送检48份性腺组织,其中24份有发育不良的睾丸,其中1份睾丸性腺中可见未分化性腺组织。19份有纤维条索性腺,1份未分化性腺组织曾被误诊为卵巢。4份可见条索状性腺伴性索状结构。所有性腺组织均未见肿瘤征象。结论MGD患儿以外阴性别模糊多见常伴苗勒管残件。临床中对考虑诊断MGD的患儿不能仅采用染色体核型分析,可疑者应完善外周血FISH性染色体嵌合型检查。MGD患儿性腺病理检查可见未分化性腺类型,病理易将其识别为卵巢组织,从而将混合性性腺发育不良误诊为卵睾型DSD。

Clinical characteristics and analysis of misdiagnosing mixed gonadal dysgenesis

Objective To explore the clinical characteristics and causes and countermeasures of misdiagnosing mixed gonadal dysgenesis(MGD).Methods From May 2013 to April 2018,clinical data were retrospectively reviewed for 24 MGD children.The average age was 21(10-39)months and the average height 83(71-97)cm.Ten children fell below the average height of the same age group by 2 standard deviations.There were 22 boys and 2 girls.The Prader grade was II(n=3),III(n=15)and IV(n=6).The results of sex hormone determination and sex-related genes were analyzed.Fluorescence in situ hybridization(FISH)for sex chromosome was further tested in 8/10 children with 46,XY chromosome.And gonad specimens were evaluated for histopathology.Results The average level of anti-mullerian hormone(AMH)was 69.42(16.57-189.92)ng/ml.The average testosterone level was 4.93(0.71-8.09)nmol/L after hCG stimulation.WT1 gene mutation was detected in 1 child with a definite diagnosis of Danis-Drash syndrome(DDS).The karyotypes were 45,X/46,XY,10 cases of 46,XY(n=12,including 8 cases confirmed by FISH as X chimeric XY),45,X/46,XY/47XYY(n=1)and 45,X/47,XYY/48XYYY(n=1).Forty-eight specimens were classified as dyspastic testis(n=24),undifferentiated gonad tissue(n=1)(previously misdiagnosed as ovary tissue)and fibrous stripe gonads with sex-cord-like structure(n=4).No evidence of malignancy was noticed.Conclusions Ambiguous genitalia is common in MGD children with Muller tube remnant.For suspected MGD children with a 46,XY chromosome,further FISH test for sex chromosome is warranted.And undifferentiated gonad tissue may be found in a streak gonad and ovary tissue is probably mistaken for making a misdiagnosis of ovotesticular DSD.