Genetic counseling for isolated GnRH deficiency

As our understanding of the complexities of the various etiologies and complex genetic architecture of GnRH deficiency grows, so too does the need to apply newly-developed genetic tools in a way that: (a) is meaningful to individuals and their families; (b) integrates all of the phenotypic features of this syndrome into a rationale; and (c) provides up-to-date diagnostic technologies in a cost-effective algorithm of genetic testing. Genetic counseling aims to accomplish these goals through ascertainment of detailed family histories, targeted comprehensive phenotypic evaluations, informed selection of genetic testing, interpretation of genetic test results, and the provision of highly specific risk assessments and psychological support to individuals diagnosed with this reproductive condition.This chapter offers a guide to incorporating this rapidly evolving state of knowledge of the pedigree and phenotypes into the process of selecting and prioritizing genetic testing. In addition, the provision of risk assessment that accounts for nuanced genetic concepts such as variable expressivity, incomplete penetrance, and oligogenicity, all of which are emerging features of the genetics of this clinical syndrome, is considered. Beyond translating genetic information, genetic counseling should address the psychological impact of embarrassment, shame, anxiety, and guilt that are often seen among individuals with reproductive disorders.

► The genetics of isolated GnRH deficiency (IGD) is growing increasingly complex. ► Variants in over 10 genes are associated with IGD and variable expressivity, reduced penetrance and oligogenicity are present. ► Uncertainty of diagnosis, infertility, and genetic issues can cause psychological stress for patients. ► Referral to a genetic professional to discuss the complexities of IGD and potential genetic testing is warranted. ► By assessing family history and patient phenotypes, genetic testing can be prioritized.