Bakjaji Shadi, Hoffman Robert P
Department of Pediatrics, Division of Endocrinology and Diabetes/The Ohio State University/Nationwide Children's Hospital, Columbus, OH, USA.
J Pediatr Endocrinol Metab. 2024 Dec 17;38(2):191-195. doi: 10.1515/jpem-2024-0501. Print 2025 Feb 25.
Kallmann syndrome (KS) is a rare genetic disorder marked by hypogonadotropic hypogonadism and either anosmia or hyposmia. It exhibits genetic heterogeneity, with mutations identified in only 30 % of cases, involving various genes such as KAL1, FGFR1, FGF8, CHD7, and SOX10. Here, we present a case of gonadotropin deficiency associated with KS, observed in both a mother and her daughter, the latter conceived through assisted reproductive technology using the mother's ovum.
A 12-year-old female presented with short stature and lack of growth over the past year. Initial laboratory testing revealed mildly elevated TSH (8.348 uIU/mL), normal free T4 (0.9 ng/dL), and positive thyroid antibodies, including elevated TPO (629 IU/mL). Her growth hormone peak response to stimulation testing was 12.8 ng/mL, and GnRH stimulation indicated a peak LH value of 1.78 mIU/mL and a peak FSH value of 2.83 mIU/mL, consistent with hypogonadotropic hypogonadism (HH). Genetic testing identified a novel heterozygous variant in the SOX10 gene, predicted to be damaging, and also present in her mother, who had Kallmann syndrome. The patient was initiated on low-dose estrogen therapy with estradiol patches to stimulate growth and pubertal development.
This case highlights the transmission of a novel SOX10 mutation in a mother-daughter pair through assisted reproductive technology, bypassing the typical infertility-related barriers to genetic inheritance in KS. The autosomal dominant inheritance pattern observed in this family emphasizes the importance of genetic counseling when reproductive assistance is considered. This case also suggests that SOX10 mutations may contribute more broadly to the pathogenesis of KS and related HH.
卡尔曼综合征（KS）是一种罕见的遗传性疾病，其特征为低促性腺激素性性腺功能减退以及嗅觉缺失或嗅觉减退。它表现出遗传异质性，仅在30%的病例中发现了突变，涉及多种基因，如KAL1、FGFR1、FGF8、CHD7和SOX10。在此，我们报告一例与KS相关的促性腺激素缺乏病例，该病例在一位母亲及其女儿身上均有观察到，后者通过使用母亲的卵子经辅助生殖技术受孕。
一名12岁女性因身材矮小且在过去一年中无生长而就诊。初始实验室检查显示促甲状腺激素轻度升高（8.348 μIU/mL），游离甲状腺素正常（0.9 ng/dL），甲状腺抗体阳性，包括甲状腺过氧化物酶升高（629 IU/mL）。她对生长激素刺激试验的峰值反应为12.8 ng/mL，促性腺激素释放激素刺激试验显示促黄体生成素峰值为1.78 mIU/mL，促卵泡生成素峰值为2.83 mIU/mL，符合低促性腺激素性性腺功能减退（HH）。基因检测在SOX10基因中发现了一种新的杂合变异，预计具有损害性，并且在其患有卡尔曼综合征的母亲身上也存在。该患者开始使用雌二醇贴片进行低剂量雌激素治疗，以刺激生长和青春期发育。
本病例突出了通过辅助生殖技术在一对母女中传递新的SOX10突变，绕过了KS中与遗传相关的典型不孕障碍。在这个家族中观察到的常染色体显性遗传模式强调了在考虑生殖辅助时进行遗传咨询的重要性。本病例还表明，SOX10突变可能在更广泛的范围内导致KS和相关HH的发病机制。
