Autosomally dominantly inherited isolated gonadotropin deficiency via maternal assisted reproduction due to SOX10 mutation

Shadi Bakjaji; Robert P. Hoffman

doi:10.1515/jpem-2024-0501

Article

Autosomally dominantly inherited isolated gonadotropin deficiency via maternal assisted reproduction due to SOX10 mutation

Shadi Bakjaji and Robert P. Hoffman

Published/Copyright: December 17, 2024

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From the journal Journal of Pediatric Endocrinology and Metabolism Volume 38 Issue 2

Abstract

Objectives

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.

Case presentation

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.

Conclusions

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.

Keywords: Kallmann syndrome; hypogonadotropic hypogonadism; short stature; SOX10 mutation; delayed puberty

Corresponding author: Shadi Bakjaji, Department of Pediatrics, Division of Endocrinology and Diabetes/The Ohio State University/Nationwide Children’s Hospital, Columbus, OH, USA, E-mail: Shadi.Bakjaji@nationwidechildrens.org

Acknowledgments

We would like to thank the patient and her family for their cooperation in allowing this case to be reported.

Research ethics: As this is a case report, formal approval from an ethics committee was not required.
Informed consent: Informed consent was obtained from the patient’s parents for publication of the case details and any accompanying images.
Author contributions: Shadi Bakjaji and Robert P. Hoffman contributed to the conception and design of the case report, data interpretation, and drafting of the manuscript. Shadi Bakjaji wrote the manuscript, while Robert P. Hoffman critically revised and approved the final version for publication. Both authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Use of Large Language Models, AI and Machine Learning Tools: None declared.
Conflict of interest: The authors state no conflict of interest.
Research funding: None declared.
Data availability: Not applicable.

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Received: 2024-10-19

Accepted: 2024-12-02

Published Online: 2024-12-17

Published in Print: 2025-02-25

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Articles in the same Issue

https://doi.org/10.1515/jpem-2024-0501

Keywords for this article

Kallmann syndrome; hypogonadotropic hypogonadism; short stature; SOX10 mutation; delayed puberty