46 XX Ovotesticular Disorder of Sex Development with Gonadotropin-Releasing Hormone Receptor, Autosomal Recessive Heterozygous Missense Mutation and Autosomal Dominant Heterozygous Missense Mutation of the PROKR2 Gene: A Case Report

TL;DR

A rare case of a 46 XX individual with both ovarian and testicular tissue is reported, involving two genetic mutations linked to Kallmann syndrome and hypogonadotropic hypogonadism.

Contribution

This is the first reported case of digenic inheritance of Kallmann syndrome in a 46 XX true hermaphrodite.

Findings

The patient had a gonadotropin-releasing hormone receptor mutation and a PROKR2 gene mutation.

The case highlights the complexity of diagnosing Kallmann syndrome due to variable hyposmia.

Digenic inheritance may contribute to rare DSD cases with overlapping clinical features.

Abstract

True hermaphroditism is a disorder of sex development (DSD), accounting for less than 5% of all DSD cases, defined by the simultaneous presence of testicular tissue and ovarian tissue in the same individual. In the reported case, the patient presented two genetic mutations involved in the pathogenic pathway of the DSD condition associated with the clinical features of Kallmann syndrome (KS), a developmental disease that associates hypogonadotropic hypogonadism (HH), due to gonadotropin-releasing hormone deficiency, and anosmia, related to the absence or hypoplasia of the olfactory bulbs. Given the variable degree of hyposmia in KS, the distinction between KS and normosmic idiopathic HH is currently unclear, especially as HH patients do not always undergo detailed olfactory testing. This syndrome is very rare, with an estimated prevalence of 1:80,000 in males and 1:40,000 in females.

This is the only case report concerning a patient with 46 XX true hermaphroditism affected by HH and digenic inheritance of Kallmann syndrome.

Figures