呈现特纳综合征表型的45，X/46，XY性发育异常患儿15例临床分析

doi:10.12372/jcp.2025.23e1238

摘要/Abstract

摘要：

目的总结呈现特纳综合征表型的45，X/46，XY性发育异常患儿的临床特点、青春期发育状况、性腺肿瘤发生情况及转归。方法回顾性分析2012年1月至2023年1月于河南省儿童医院就诊的呈现特纳综合征表型的45，X/46，XY性发育异常患儿的临床资料。结果 15例患儿均为女性表型，伴生长发育迟缓，有颈蹼、肘外翻等典型特纳综合征临床特征；3例呈现自发性乳房发育，1例自发性月经初潮，最终均出现性腺发育不良。染色体中Y染色体嵌合比率为5%~85%。10例进行SRY基因检测，均为阳性。7例性腺切除后进行病理检查，发现3例性腺肿瘤（1例单侧性腺母细胞瘤、1例无性细胞瘤和1例原位生殖细胞瘤），其中1例原位生殖细胞瘤在诊断时已恶变，诊断年龄为4.3岁。结论 45，X/46，XY性发育异常部分患儿可呈现类似特纳综合征的临床特征，性腺肿瘤发生率和恶变率高，恶变年龄小，临床上对此应予以充分的重视，及时评估手术介入的必要性。

关键词: 性发育异常, Y染色体嵌合, SRY基因, 性腺母细胞瘤, 生殖细胞瘤

Abstract:

Objective To summarize the clinical features, puberty development, gonadal neoplasia and prognosis of 15 children with 45, X/46, XY disorders of sex development (DSD) presenting Turner syndrome phenotype. Methods The clinical data of 15 children with 45, X/46, XY DSD presenting Turner syndrome phenotype in Henan Children's Hospital from January 2012 to January 2023 were retrospectively analyzed. Results All the 15 patients presented with the female phenotype and had growth retardation. They had typical clinical signs of Turner syndrome, such as neck web and cubitus valgus. Spontaneous breast development occurred in 3 patients, spontaneous menarche occurred in 1 patient, and gonadal dysgenesis eventually occurred in all patients. The Y chromosome mosaicism rate was 5%-85%. SRY gene detection was performed in 10 patients, and all of them were positive. Pathological examination of 7 patients after gonadectomy revealed gonadal tumors in 3 patients (1 case of unilateral gonadoblastoma, 1 case of dysgerminoma, and 1 case of insitu germ cell tumor). One case of insitu germ cell tumor was malignant at the time of diagnosis, and the age of diagnosis was 4.3 years. Conclusions Patients with 45, X/46, XY DSD may exhibit clinical features reminiscent of Turner syndrome. They have a higher incidence and risk of malignant transformation of gonadal tumors, and this transformation tends to occur at a younger age. This should be given full attention in clinical practice, and the necessity of surgical intervention should be evaluated promptly.

Key words: disorder of sexual development, mosaic Y chromosome, SRY gene, gonadoblastoma, germ cell tumor

刘晓景, 刘素华, 高静, 郝会民, 卫海燕, 刘敏. 呈现特纳综合征表型的45，X/46，XY性发育异常患儿15例临床分析[J]. 临床儿科杂志, 2025, 43(5): 345-349.

LIU Xiaojing, LIU Suhua, GAO Jing, HAO Huimin, WEI Haiyan, LIU Min. Clinical analysis of 15 children with 45, X/46, XY disorders of sex development presenting Turner syndrome phenotype[J]. Journal of Clinical Pediatrics, 2025, 43(5): 345-349.

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参考文献 18

[1]	中华医学会儿科学分会内分泌遗传代谢学组. 性发育异常的儿科内分泌诊断与治疗共识[J]. 中华儿科杂志, 2019, 57(6): 410-418.
	The Subspecialty Group of Endocrinologic, Hereditary and Metabolic Diseases, the Society of Pediatrics, Chinese Medical Association. Consensus statement on the diagnosis and endocrine treatment of children with disorder of sex development[J]. Zhonghua Erke Zazhi, 2019, 57(6): 410-418.
[2]	中华医学会内分泌学分会性腺学组. 特纳综合征诊治专家共识[J]. 中华内分泌代谢杂志, 2018, 34(3): 181-186.
	Division of Gonadal disease, Chinese Society of Endocrinology. Expert consensus on diagnosis and treatment of Turner syndrome[J]. Zhonghua Neifenmi Daixie Zazhi, 2018, 34(3): 181-186.
[3]	Steiner M, Saenger P. Turner syndrome: an update[J]. Adv Pediatr, 2022, 69(1): 177-202. doi: 10.1016/j.yapd.2022.03.004 pmid: 35985709
[4]	Debo B, Van Loocke M, De Groote K, et al. Multidisciplinary approach to the child with sex chromo-somal mosaicism including a Y-containing cell line[J]. Int J Environ Res Public Health, 2021, 18(3): 917.
[5]	Gravholt CH, Viuff MH, Brun S, et al. Turner syndrome: mechanisms and management[J]. Nat Rev Endocrinol, 2019, 15(10): 601-614. doi: 10.1038/s41574-019-0224-4 pmid: 31213699
[6]	Gravholt CH, Andersen NH, Christin-Maitre S, et al. Clinical practice guidelines for the care of girls and women with Turner syndrome[J]. Eur J Endocrinol, 2024, 190(6): G53-G151.
[7]	Guzewicz L, Howell S, Crerand CE, et al. Clinical phenotype and management of individuals with mosaic monosomy X with Y chromosome material stratified by genital phenotype[J]. Am J Med Genet A, 2021, 185(5): 1437-1447.
[8]	Viuff M, Skakkebaek A, Nielsen MM, et al. Epigenetics and genomics in Turner syndrome[J]. Am J Med Genet C Semin Med Genet, 2019, 181(1): 68-75.
[9]	Dowlut-McElroy T, Gomez-Lobo V. Gonadectomy in individuals with Turner syndrome and Y chromosome material: fertility considerations[J]. J Pediatr Adolesc Gynecol, 2022, 35(4): 415-416.
[10]	Meccanici F, Schotte MH, Snoeren M, et al. Aortic dilation and growth in women with Turner syndrome[J]. Heart, 2022, 109(2): 102-110. doi: 10.1136/heartjnl-2022-320922 pmid: 35705330
[11]	Dabrowski E, Johnson EK, Patel V, et al. Turner syndrome with Y chromosome: spontaneous thelarche, menarche, and risk of malignancy[J]. J Pediatr Adolesc Gynecol, 2020, 33(1): 10-14.
[12]	Nadesapillai S, van der Velden J, van der Coelen S, et al. TurnerFertility trial: fertility preservation in young girls with Turner syndrome by freezing ovarian cortex tissue-a prospective intervention study[J]. Fertil Steril, 2023, 120(5): 1048-1060. doi: 10.1016/j.fertnstert.2023.08.004 pmid: 37549836
[13]	Karila D, Donadille B, Léger J, et al. Prevalence and characteristics of gonadoblastoma in a retrospective multi-center study with follow-up investigations of 70 patients with Turner syndrome and a 45, X/46, XY karyotype[J]. Eur J Endocrinol, 2022, 187(6): 873-881.
[14]	Andrade JGR, Fabbri-Scallet H, Dos Santos AP, et al. Clinical findings and follow-up of 46,XY and 45,X/46,XY testicular dysgenesis[J]. Sex Dev, 2019, 13(4): 171-177. doi: 10.1159/000504239 pmid: 31816618
[15]	Aversa T, De Sanctis L, Faienza MF, et al. Transition from pediatric to adult care in patients with Turner syndrome in Italy: a consensus statement by the TRAMITI project[J]. J Endocrinol Invest, 2024, 47(7): 1585-1598. doi: 10.1007/s40618-024-02315-4 pmid: 38376731
[16]	Dowlut-McElroy T, Gomez-Lobo V. Gonadectomy in individuals with Turner syndrome and Y chromosome material: fertility considerations[J]. J Pediatr Adolesc Gynecol, 2022, 35(4): 415-416.
[17]	Liu S, Zheng J, Liu X, et al. Comprehensive analysis of three female patients with different types of X/Y translocations and literature review[J]. Mol Cytogenet, 2023, 16(1): 7. doi: 10.1186/s13039-023-00639-z pmid: 37202823
[18]	中华预防医学会, 生育力保护分会, 生殖内分泌生育保护学组. 性发育异常分类与诊断流程专家共识[J]. 生殖医学杂志, 2022, 31(7): 871-875.
	Reproductive endocrinology and Fertility Preservation Section of Chinese Society on Fertility Preservation under Chinese Preventive Medicine Association. Consensus on classification and clinical diagnostic flowchart of disorders of sex development[J]. Shengzhi Yixue Zazhi, 2022, 31(7): 871-875.

患儿	确诊年龄/岁	染色体核型（%）	身高/cm(SD)	TS体征及并发症
例1	14	45，X(83.3)/46，XY(16.7)	145.0(-3SD)	颈蹼、乳距宽、智力发育落后
例2	17	45，X/46，XY	150.0(-2SD)	乳距宽
例3	14	45，X(20)/46，XY(80)	140.7(-3.3SD)	颈蹼、乳距宽
例4	18	45，X(30)/46，XY(70)	148.0(-2.4SD)	乳距宽、乳房发育似B3期，月经初潮1次
例5	13	45，X(95)/46，XY(5)	138.0(-3SD)	乳距宽、盾状胸、面部多痣、肘外翻；并发症：糖耐量异常
例6	10	45，X(80)/46，XY(20)	124.2(-2.5SD)	颈短、发际线低、乳距宽；有乳房发育
例7	11.6	45，X(30)/46，XY(70)	127.7(-3.3SD)	乳距宽
例8	11	45，X(70)/46，XY(30)	124.8(-3.3SD)	内眦赘皮、乳距宽
例9	14	45，X(15)/46，XY(85)	138.6(-3.6SD)	肘外翻、乳距宽
例10	14	45，X(32)/46，XY(68)	143.0(-2.8SD)	肘外翻、第四掌骨短、颈蹼、发际线低，并发症：心电图二联律、三联律
例11	7	45，X(16)/46，XY(84)	114.0(-1.7SD)	乳距宽
例12	7.4	45，X(71.2)/46，XY(28.8)	109.2(-3SD)	无肘外翻
例13	13.8	45，X(52)/46，XY(28)/47，XYY(20)	129.0(-5.3SD)	肘外翻、内眦赘皮；乳房发育
例14	4.3	45，X(28)/46，XY(72)	94.6(-2.6SD)	内眦赘皮；升主动脉内径稍宽，永存左上腔静脉
例15¹⁾	13	45，X(83.3)/46，X，Del(Y)(16.7)	145.0(-2.9SD)	眼距稍宽

患儿	FSH/mIU·mL^-1	LH/mIU·mL^-1	E₂/pg·mL^-1	T(HCG激发前）/ng·mL^-1	T(HCG激发后）/ng·mL^-1	AMH/ng·mL^-1
例1	74.00	23.10	11.72	0.16	0.31	-
例2	17.97	2.83	27.90	0.15	0.54	0.08
例3	205.00	25.84	19.00	0.23	-	-
例4	89.46	24.85	<5	0.05	-	-
例5	136.00	19.24	<5	0.15	0.12	<0.06
例6	24.02	4.01	11.72	0.13	0.26	-
例7	61.81	16.77	10.26	0.04	-	-
例8	115.80	22.90	<5	<0.01	-	-
例9	79.98	18.68	23.00	0.33	-	-
例10	68.90	26.62	12.23	<0.01	-	-
例11	21.13	0.72	<10	<0.01	<0.01	0.59
例12	103.80	11.72	<5	<0.01	0.14	-
例13	59.70	13.90	8.17	0.02	0.37	-
例14	29.00	1.20	<5	<0.01	<0.01	<0.07
例15	133.07	26.58	1.56	0.23	0.28	-

患儿	性腺彩色多普勒超声	SRY基因	性腺病理
例2	双侧卵巢未探及	阳性	输卵管组织，（左侧性腺）可疑卵巢组织
例5	子宫20 mm×14 mm×10 mm，宫颈17 mm，左侧卵巢 21 mm×8 mm×9 mm，右侧13 mm×12 mm×10 mm	阳性	左侧卵巢为纤维脂肪组织，右侧可见性腺母细胞瘤
例6	子宫幼稚型21.6 mm×4.3 mm，双侧卵巢未显示	阳性	双侧卵巢实质内未见睾丸组织成分
例11	子宫20 mm×14 mm×10 mm，宫颈17 mm，左侧卵巢 21 mm×8 mm×9 mm，右侧13 mm×12 mm×10 mm	阳性	原位生殖细胞瘤、小灶恶性变
例12	膀胱后可见条索样子宫、双侧卵巢未显示	阳性	未见明确睾丸组织及卵细胞，可见纤维组织
例13	左侧卵巢19.9 mm×7.8 mm×10.6 mm，右侧卵巢 18.5 mm×7.9 mm×7.6 mm，膀胱后方可见一低回声带，厚约5.2 mm	阳性	未见明显卵母细胞