瓦登伯格综合征合并原发性闭经和身材矮小一例报道及文献复习

doi:10.16150/j.1671-2870.2025.04.013

诊断学理论与实践 ›› 2025, Vol. 24 ›› Issue (04): 455-458.doi: 10.16150/j.1671-2870.2025.04.013

瓦登伯格综合征合并原发性闭经和身材矮小一例报道及文献复习

姚昕¹, 李梦洁²^,³, 叶山东³, 郑茂³()

1.桐城市人民医院内分泌科，安徽桐城 231400
2.蚌埠医科大学研究生院，安徽蚌埠 233030
3.中国科学技术大学附属第一医院（安徽省立医院）内分泌科，安徽合肥 230001

收稿日期:2024-11-05 接受日期:2025-03-29 出版日期:2025-08-25 发布日期:2025-09-09
通讯作者: 郑茂E-mail：zhengmao1999@foxmail.com

A case report of Waardenburg syndrome with primary amenorrhea and short stature， and a review of literature

YAO Xin¹, LI Mengjie²^,³, YE Shandong³, ZHENG Mao³()

1. Department of Endocrinology, Tongcheng People's Hospital, Anhui Tongcheng 231400, China
2. Graduate School of Bengbu Medical University, Anhui Bengbu 233030, China
3. Department of Endocrinology, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Anhui Hefei 230001, China

Received:2024-11-05 Accepted:2025-03-29 Published:2025-08-25 Online:2025-09-09

摘要/Abstract

摘要：

本文报道1例17岁女性患者，因第二性征未发育和原发性闭经就诊。患者临床表现为听力下降、虹膜呈蓝色、双内眦增宽，并伴有身材矮小、双侧肘外翻及盾状胸。实验室检查提示低促性腺激素性性腺功能减退，同时合并不完全性生长激素缺乏。彩超检查显示始基子宫。全外显子组测序发现其SOX10基因存在c.1029dup （p.Thr344Hisfs*58）突变，确诊为瓦登伯格综合征（Waardenburg syndrome， WS）。Sanger测序验证该突变为新发突变，目前公共数据库中尚未收录该突变。家系调查结果显示，患者父母的外周血样本中未检出该突变。本报道突变丰富了WS疾病基因突变谱和临床相关数据。对于存在不明原因听力障碍、色素沉着异常伴生长发育迟缓的儿童，应考虑SOX10基因突变可能，尽早行基因检测以明确诊断。

关键词: SOX10, 瓦登伯格综合征, 色素沉着异常, 低促性腺激素性性腺功能减退症, 听力丧失

Abstract:

This article reports a case of a 17-year-old female patient who presented with absent secondary sexual characteristics and primary amenorrhea. The patient's clinical manifestations included hearing loss, blue irides, and telecanthus, accompanied by short stature, bilateral cubitus valgus, and shield-shaped chest. Laboratory tests indicated hypogonadotropic hypogonadism with partial growth hormone deficiency, and ultrasound revealed a rudimentary uterus. Whole-exome sequencing identified a c.1029dup (p.Thr344Hisfs*58) mutation in the SOX10 gene, confirming the diagnosis of Waardenburg syndrome (WS). Sanger sequencing confirmed that this was a de novo mutation, which has not been reported in public databases. Family investigation showed that the mutation was not detected in peripheral blood samples from the patient's parents. This mutation expands the genetic mutation spectrum and clinical data of WS. In cases of unexplained hearing impairment, abnormal pigmentation, and growth retardation in children, SOX10 gene mutation should be conside-red, and genetic testing should be performed early to establish a diagnosis.

Key words: SOX10, Waardenburg syndrome, Dyspigmentation, Hypogonadotropic hypogonadism, Hearing loss

中图分类号:

R596
R446

姚昕, 李梦洁, 叶山东, 郑茂. 瓦登伯格综合征合并原发性闭经和身材矮小一例报道及文献复习[J]. 诊断学理论与实践, 2025, 24(04): 455-458.

YAO Xin, LI Mengjie, YE Shandong, ZHENG Mao. A case report of Waardenburg syndrome with primary amenorrhea and short stature， and a review of literature[J]. Journal of Diagnostics Concepts & Practice, 2025, 24(04): 455-458.

图/表 4

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参考文献 18

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[3]	LI Y, CHEN Y, SUN Y, et al. Waardenburg syndrome type 2 with a de novo variant of the SOX10gene: a case report[J]. BMC Med Genomics, 2024, 17(1):104-111.
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	REN J, YAN X H, ZHANG M Y, et al. Vardenberg syndrome with hypogonadism: a case report and literature review[J]. China Clin Case Database, 2023, 5(1):E02338-E02338.
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指标	数值	正常范围
游离三碘甲腺原氨酸	6.84	3.70~6.93 pmol/L
游离甲状腺激素	13.13	11.61~21.41 pmol/L
促甲状腺激素	2.602	0.51~4.94 mIU/L
血清皮质醇	426.09	117.50~686.85 mmol/L
促肾上腺皮质激素	43.10	0~46 pg/mL
生长激素	0.23	0.123~8.050 ng/mL
胰岛素样生长因子1	210.00	190~429 ng/mL
胰岛素样生长因子结合蛋白3	7.15	3.4~9.5 ng/mL

时间	FSH (IU/L)	LH (IU/L)	E2 (pg/mL)
0 min	<0.3	0.47	<5.00
30 min	1.56	1.88	<5.00
60 min	1.96	2.07	<5.00
90 min	2.50	2.33	<5.00
120 min	2.98	2.42	<5.00
240 min	3.45	1.69	<5.00
24 h	0.66	0.87	<5.00

病例	文献	国家	性别	年龄（岁）	WS表型	IHH诊断	其他表型	SOX10突变
1	本文	中国	女	17	HL、 DP	nIHH	双侧内眦增宽，身材矮小，双侧肘外翻，盾状胸	c.1029dup（p.Thr34 Hisfs*58）
2	Li等^[3]	中国	女	28	HL、 DP	nIHH	系统性红斑狼疮	c. 175 C > T（p. Q59X）
3	任洁等^[4]	中国	男	18	HL、 DP	nIHH	鼻根略宽大	c.336G>T（p.Met112Ile）
4	Wang等^[5]	中国	男	18	HL、 DP	KS	骨龄推迟（骨龄约13岁）	22q13.1 微缺失
5	Chen等^[6]	中国	男	28	HL、 DP	KS	肥胖，双侧乳房增大伴轻度压痛及乳腺结节	c.1179_1180insACTATGGCTCAGCCTTCCCC（p.Ser394fs）
6	Wang等^[7]	中国	男	30	HL、 DP	KS	身材矮小，甲状腺功能亢进症	c.565G>T（p.E189X）
7	Izumi等^[8]	日本	女	14	HL、 DP	nIHH	身材矮小	c.506delC（p.P169fsX117）
8	Suzuki等^[9]	日本	男	15	HL、 DP	KS	无	c.434T>C（p.Leu145Pro）
9	Vaaralahti等^[10]	芬兰	男	17	HL	KS	无	c.184G>T （p.Glu62X）
10	Parry等^[11]	美国	男	30	HL、 DP	nIHH	白内障，头小，关节活动受限，骨肉瘤	/

瓦登伯格综合征合并原发性闭经和身材矮小一例报道及文献复习

A case report of Waardenburg syndrome with primary amenorrhea and short stature， and a review of literature

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