Genes predisposing to syndromic and nonsyndromic infertility: a narrative review

TL;DR

This review summarizes 65 genes linked to syndromic and nonsyndromic infertility, highlighting gene-specific mechanisms and potential targeted treatments for improved management of infertility.

Contribution

It provides an updated comprehensive overview of genetic factors involved in infertility, distinguishing between syndromic and nonsyndromic cases and their specific gene associations.

Findings

65 genes linked to infertility identified

35% associated with syndromic infertility

48% predispose to male infertility

Abstract

Background: Advanced biological techniques have helped produce more insightful findings on the genetic etiology of infertility that may lead to better management of the condition. This review provides an update on genes predisposing to syndromic and nonsyndromic infertility. Main body: The review identified 65 genes linked with infertility and infertility-related disorders. These genes regulate fertility. However, mutational loss of the functions of the genes predisposes to infertility. Twenty-three (23) genes representing 35% were linked with syndromic infertility, while 42 genes (65%) cause nonsyndromic infertility. Of the 42 nonsyndromic genes, 26 predispose to spermatogenic failure and sperm morphological abnormalities, 11 cause ovarian failures, and 5 cause sex reversal and puberty delay. Overall, 31 genes (48%) predispose to male infertility, 15 genes (23%) cause female infertility, and 19 genes (29%) predispose to both. The common feature of male infertility was spermatogenic failure and sperm morphology abnormalities, while ovarian failure has been the most frequently reported among infertile females. The mechanisms leading to these pathologies are gene-specific, which, if targeted in the affected, may lead to improved treatment. Conclusions: Mutational loss of the functions of some genes involved in the development and maintenance of fertility may predispose to syndromic or nonsyndromic infertility via gene-specific mechanisms. A treatment procedure that targets the affected gene(s) in individuals expressing infertility may lead to improved treatment.