性别发育异常的评估、诊断和治疗研究进展

doi:10.3785/j.issn.1008-9292.2019.08.02

浙江大学学报（医学版）

2019, Vol. 48

Issue (4): 358-366 DOI: 10.3785/j.issn.1008-9292.2019.08.02

专题报道

性别发育异常的评估、诊断和治疗研究进展

陈光杰(

),王晓豪,唐达星*(

)

浙江大学医学院附属儿童医院泌尿外科, 浙江杭州 310003

Progress on evaluation, diagnosis and management of disorders of sex development

CHEN Guangjie(

),WANG Xiaohao,TANG Daxing*(

)

Department of Urology, the Children's Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China

全文: PDF(928 KB)

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摘要：

性别发育异常（DSD）是指由于先天性的染色体、性腺或性别解剖结构发育出现异常，导致疾病谱广泛、有不同病理生理改变且临床表现各异的一组疾病，新生儿常表现为生殖器异常，而青少年则表现为青春发育期异常的性发育。随着对DSD的深入研究，国际上已形成共识，即DSD的基本临床评估（内外生殖器及内分泌激素）、诊断建立（包括染色体、基因诊断）、患儿及家庭的心理评估、治疗（包括性别分配、激素的替代及外科手术选择）、潜在的生育能力保护及长期的追踪随访等一系列工作已非小儿泌尿外科单一学科能承担，需要小儿内分泌科，小儿泌尿外科、临床心理科、遗传学科、影像学科及其他相关学科的共同参与。本文就近年来DSD的评估、诊断和治疗等方面的进展作一综述。

关键词： 性发育障碍/诊断; 性发育障碍/治疗; 规范; 综述

Abstract:

Disorders of sex development (DSD) refer to a group of diseases characterized by abnormal congenital development of chromosomes, gonad or genitals with different pathophysiological changes and clinical manifestations. DSD is more common in neonates and adolescents, and neonates often show genital abnormalities while adolescents show abnormal sexual development during puberty. It is the international consensus that the scope of DSD should include basic clinical evaluation (internal and external genitalia and endocrine hormones), diagnostic confirmation (chromosome, genetic diagnosis), psychological assessment for children and family, treatment (sex assignment, hormone replacement and surgical intervention), potential fertility protection and long-term follow-up, which require the expertise of pediatric endocrinology, pediatric urology, clinical psychology, genetic disciplines, medical images and other related disciplines; that is, individualized management of children with DSD requires an experienced multidisciplinary team (MDT). This article reviews the recent progress on the evaluation, diagnosis and management of disorders of sex development.

Key words: Disorders of sex development/diagnosis Disorders of sex development/therapy Benchmarking Review

收稿日期: 2019-03-13 出版日期: 2019-10-30

R726.9

基金资助: 国家重点研发计划(2018YFC1002700)

通讯作者: 唐达星 E-mail: dr.chenguangjie@zju.edu.cn;tangdx0206@zju.edu.cn

作者简介: 陈光杰(1978—), 男, 硕士, 副主任医师, 主要从事小儿泌尿外科学研究; E-mail: dr.chenguangjie@zju.edu.cn; https://orcid.org/0000-0002-5561-2237

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引用本文:

陈光杰,王晓豪,唐达星. 性别发育异常的评估、诊断和治疗研究进展[J]. 浙江大学学报（医学版）, 2019, 48(4): 358-366.

CHEN Guangjie,WANG Xiaohao,TANG Daxing. Progress on evaluation, diagnosis and management of disorders of sex development. J Zhejiang Univ (Med Sci), 2019, 48(4): 358-366.

链接本文:

http://www.zjujournals.com/med/CN/10.3785/j.issn.1008-9292.2019.08.02 或 http://www.zjujournals.com/med/CN/Y2019/V48/I4/358

基因	蛋白质	基因座	遗传特性	性腺	米勒管结构	外生殖器	伴发临床特点
AD：常染色体显性遗传；AR：常染色体隐性遗传；CAH：先天性肾上腺皮质增生.
单个基因
WT1	转录因子	11p13	AD	发育不全睾丸	阳性/阴性	模棱两可至完全女性外阴	WAGR综合征、Denys-Drash和Frasier综合征
SF1	核受体转录因子	9q33	AD/AR	发育不全睾丸	阳性/阴性	模棱两可至完全女性外阴	严重者合并原发性肾上腺功能衰竭、轻者单发部分性性腺发育不全
SRY	转录因子	Yp11.3	Y连锁遗传	发育不全睾丸或卵睾	阳性/阴性	模棱两可至完全女性外阴
SOX9	转录因子	17q24~25	AD	发育不全睾丸或卵睾	阳性/阴性	模棱两可至完全女性外阴	躯干发育异常
DHH	信号分子	12q13.1	AR	发育不全睾丸	阳性	完全女性外阴	严重者合并微束神经病变
ATRX	解旋酶	Xq13.3	X连锁遗传	发育不全睾丸	阴性	男性、模棱两可或完全女性外阴	合并α地中海贫血、智力发育迟缓
引起染色体改变的关键候补基因
DMRT1	转录因子	9P24.3	单体缺失	发育不全睾丸	阳性/阴性	模棱两可至完全女性外阴	智力发育迟缓
DAX1	核受体转录因子	Xp21.3	Xp21复制	发育不全睾丸或卵巢	阳性/阴性	模棱两可至完全女性外阴	合并智力发育迟缓、唇腭裂等畸形
WNT4	信号分子	1p35	1p35复制	发育不全睾丸	阳性	模棱两可	合并智力发育迟缓、唇腭裂、宫内发育迟缓、小头畸形、法洛四联症等
导致激素合成或作用异常的基因
LHGCR	G蛋白受体	2p21	AR	睾丸	阴性	模棱两可至完全女性外阴或小阴茎	Leydig细胞发育不全
DHCR7	酶	11q12~13	AR	睾丸	阴性	男性、模棱两可或完全女性外阴	Smith-Lemli-Opitz综合征
STAR	线粒体膜蛋白	8p11.2	AR	睾丸	阴性	完全女性外阴	先天性类脂性肾上腺增生、青春期发育障碍
CYP11A1	酶	15q23~24	AR	睾丸	阴性	模棱两可或完全女性外阴	CAH、青春期发育障碍
HSD3B2	酶	1p13.1	AR	睾丸	阴性	模棱两可	CAH、原发性肾上腺功能衰竭
CYP17	酶	10q24.3	AR	睾丸	阴性	模棱两可至完全女性外阴或小阴茎	CAH、高血压
POR(P450氧化还原酶)	CYP酶电子供体	7q11.2	AR	睾丸	阴性	男性，模棱两可	Antley-Bixler综合征
HSD17B3	酶	9q22	AR	睾丸	阴性	模棱两可或完全女性外阴	青春期男性化不全
SRD5A2	酶	2p23	AR	睾丸	阴性	模棱两可或小阴茎	青春期男性化不全
AMH	信号分子	19p13.3~13.2	AR	睾丸	阳性	正常男性表型	米勒管永存综合征
AMH受体	丝氨酸/苏氨酸激酶跨膜受体	12q13	AR	睾丸	阳性	正常男性表型	米勒管永存综合征、双侧隐睾
AR	核受体转录因子	Xq11~12	X连锁遗传	睾丸	阴性	男性、模棱两可、小阴茎或完全女性外阴	完全性雄激素不敏感综合征、部分性雄激素不敏感综合征

表 1 46, XY性别发育异常相关基因一览表

表 2 不同性别发育异常疾病性腺恶变风险

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