Intersex conditions (also known as Differences of Sex Development) are congenital conditions in which development of chromosomal, gonadal or anatomical sex is atypical. Commonly, intersex conditions cause gonadal dysgenesis due to mutations in genes required during fetal life for gonadal development. These genes often play a role in other organ systems. Such extra-gonadal effects of these mutations lead to co-morbidities or syndromic forms of intersex conditions. In this talk, several examples of Syndromic DSD in 46,XY patients will be discussed. Firstly, variants in the FGF9 ligand or in its receptor, FGFR2 occur in 46,XY intersex patients, some with synostoses. FGF signalling variants affect Sertoli cell differentiation or proliferation. Secondly, a form of alpha thalassemia occurs in patients with ATRX syndrome leading to under virilisation or feminisation of XY individuals. In an ATRX mouse knockout model, the formation of a ‘giant’ PML nuclear body in Sertoli cells leads to testis degeneration. Thirdly, a number of intersex cases of unknown genetic etiology are under study and undergoing whole exome and whole genome analyses. These patients have rare co-morbidities, such as intellectual disability, heart and kidney defects, tall stature, and advanced bone age.
See posters by Uyen Le et al., Brittany Croft et al., and Nayla Leon Carlos et al.