Genetics of hypogonadotropic hypogonadism
Adam C Millar1,2, Hanna Faghfoury1,3, Jared M Bieniek4
1Department of Medicine, University of Toronto, Toronto, ON, Canada.
Translational Andrology and Urology
|April 14, 2021
Summary
Male congenital hypogonadotropic hypogonadism (CHH) is a genetic disorder affecting the reproductive axis. Advances in genetic testing, including next-generation sequencing, improve diagnosis and understanding of CHH causes.
Area of Science:
- Endocrinology
- Genetics
- Reproductive Medicine
Background:
- Male congenital hypogonadotropic hypogonadism (CHH) results from impaired gonadotropin-releasing hormone (GnRH) production or action.
- This leads to hypothalamic-pituitary-gonadal axis dysfunction, causing low testosterone and infertility.
- Over 30 genes are implicated, but less than 50% of cases are genetically diagnosed, often termed idiopathic hypogonadotropic hypogonadism.
Purpose of the Study:
- To review the genetic basis of CHH.
- To discuss advancements in genetic testing strategies for CHH.
- To outline current treatment approaches for CHH.
Main Methods:
- Review of current literature on CHH genetics and diagnostics.
- Analysis of genetic testing strategies, including next-generation sequencing.
- Summary of clinical presentation, diagnosis, and treatment options.
Main Results:
- Genetic testing has identified over 30 genes associated with CHH.
- Next-generation sequencing enables simultaneous testing of multiple genes, improving diagnostic yield.
- Clinical history, physical exam, and lab features aid in identifying syndromic CHH or associated pituitary deficiencies.
Conclusions:
- CHH is a complex genetic disorder with significant diagnostic challenges.
- Modern genetic sequencing techniques are crucial for identifying causative mutations.
- Treatment is tailored to fertility desires, utilizing hormonal therapies like hCG, rFSH, or testosterone replacement.
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