Genetic disorders of sex development in cats: An update

Disorders of sex development (DSD) are rarely reported in cats, but this does not mean these occurrences are an insignificant reproductive and health problem in this species. The DSD condition affects reproduction and can be associated with an increased risk of gonadal tumorigenesis. In this review, an overview of findings since 2012 are presented that focus on cytogenetic and molecular genetic studies of cats with abnormal external genitalia. Results from advanced cytogenetic analysis of sex chromosomes indicate there is a range of abnormalities, including aneuploidies, structural rearrangements and freemartinism, which manifests as leukocyte XX/XY chimerism. The molecular abnormalities that result in feline monogenic and multifactorial DSD (such as hypospadias and cryptorchidism) are very few. There are only two mutations of genes (CYP11B1 and TAC3) which are known to be responsible for syndromes associated with abnormal sexual development. Several candidate genes (SRY, AR, SRD5A2, MAMLD1, DHH, HSD3B2, and HSD17B3) have also been examined, but no associations were identified between these polymorphisms and DSD phenotypes. The findings in developing the present review indicate sex chromosome abnormalities are quite common causes of feline DSD. The study of the molecular disorders that lead to the development of DSD in cats with normal XX or XY sex chromosome complements is still in its infancy, and further research is needed into this topic. It can be anticipated that the use of next generation sequencing technologies to study the genetic disorders that result in the DSD condition in cats will lead to an increase the detection of several causative mutations.