Objective: To explore the feasibility of gender assignment in 46,XY disorders of sex development (DSD) with severe undermasculinisation mainly based on molecular diagnosis. Methods: A retrospective study of 45 patients of 46, XY DSD with severe undermasculinisation were admitted between November 2015 and October 2018 at Children's Hospital, Zhejiang University School of Medicine. The initial social gender were all female, of whom the external genital manifestations were Prader 0 to 2; the degree of masculinity was scored using external masculinisation score (EMS); the position and development of the gonads were examined by ultrasound, cystoscopy and laparoscopy, also including assessing the development of the Wolffian tube and the Müllerian tube. The level and ratio of testosterone to dihydrotestosterone before and after hCG stimulation were evaluated for the function of Leydig cell and 5α-reductase-2. Gender role scales and sandbox games were used to assess gender role behavior. Genital sensitivity to androgen stimulation was assessed; A panel including 163 genes related to gender development were determined by second-generation sequencing in all 45 patients. Finally, a multidisciplinary team (MDT) makes a gender assignment after a comprehensive analysis mainly based on the molecular etiological diagnosis. Results: Thirty-nine out of 45 patients (87%) had an identifiable genetic etiology, and the remaining 6 (13%) were negative for genetic testing. Forty-five patients had EMS less than or equal to 3 points. Sexual psychological assessment was performed in 39 patients, with male dominance in 24 (62%) and female dominance in 15 (38%). The gender assignment was 23 cases (51%) for male and 19 cases (42%) for female, and 3 cases (7%) were not completely determined. Conclusions: Molecular diagnosis provides a strong basis for appropriate gender assignment of 46, XY DSD children with severe undermasculinisation. Based on molecular diagnosis, each DSD should be analyzed by professional MDT to analyze the clinical symptoms/signs, gonadal development, gonad tumor risk, external genital morphology, sexual psychological assessment, potential fertility opportunities, parental views, Social and cultural factors, etc. make appropriate gender assignment.
目的： 探讨主要以分子诊断为主要依据对重度雄性化不全46，XY性发育异常（DSD）患儿进行性别认定的可行性。 方法： 回顾性研究2015年11月至2018年10月浙江大学医学院附属儿童医院收治的45例重度雄性化不全的46，XY DSD患儿，初诊性别为女性，外生殖器表现为Prader 0~2级；采用外生殖器雄性化评分（EMS）对雄性化程度进行评分；超声、膀胱镜和腹腔镜检查睾丸的位置和发育情况，同时了解华菲管和苗勒管发育情况；测定绒毛膜促性腺激素激发前、后睾酮和双氢睾酮水平及比值来了解睾丸间质细胞和5α还原酶的功能；采用性别角色量表和沙盘游戏评估性别角色行为；评估外生殖器对雄激素刺激的敏感性；通过二代测序法测定163个性发育相关基因，45例患儿均行性发育相关基因Panel检查；最后由多学科团队（MDT）在分子学病因诊断的基础上综合分析作出合适的性别认定。 结果： 45例患儿中39例（87%）存在明确的基因致病变异，6例（13%）阴性发现。45例患儿EMS均≤3分。39例（87%）进行了性心理评估，其中男性优势24例（62%），女性优势15例（38%）。性别认定为男性23例（51%），女性19例（42%），未完全确定3例（7%）。 结论： 分子诊断为重度雄性化不全的46，XY DSD患儿合适的性别认定提供了强有力的依据。每个DSD患儿都应该由专业MDT在分子诊断的基础上，通过综合分析患儿的临床症状和体征、性腺发育、性腺肿瘤风险、外生殖器形态、性心理评估、潜在的生育机会、父母的观点、社会文化环境因数等作出合适的性别认定。.
Keywords: 46, XY Disorders of sex development; Gender Determination; Gene; Virilism.