Background: In this study we investigated the genetic aetiology of a series patients with DSD seen in Ukraine.
Materials and Methods: The Ukraine Pediatric DSD Register has 95 children with DSD between the ages of 0-18 y.o. in 2018 (a prevalence of 1 in 80097). The criterion for including patients to the database was ambiguous genitalia and/or a discrepancy between the chromosomal and gonadal/genital sex. All patients had a karyotype performed and, if necessary, fluorescence in situ hybridization (FISH). We studied 30 probands with 46,XX or XY DSD for further exome sequencing studies.
Results and Discussion: Sex chromosome DSD was diagnosed in 17.9% (n=17), 46,XY DSD in 68.4% (n=65), 46,XX DSD in 13.7% cases (n=13). The most frequent variant of the karyotype among the first group was 45,X/46,XY (n=6; 35.2%). In a group of patients with 46,XX DSD we diagnosed: testicular 46,XX DSD (n=5), 21-hydroxylase deficiency with virilization IV-V degree by Prader (n=4), 46,XX gonadal dysgenesis (n=3) and DSD in VACTER-association (n=1). 3 patients were SRY positive. In a group of patients with 46,XY DSD 40 patients (61.5%) were registered in female sex, 25 patients (38.5%) as males. However in 46,XX group 8 patients (61.5%) were registered as males.
Genetic testing in 46,XY/XX DSD group was done in 30 (38.4%) cases. We determined the genetic etiology in 18 of 30 (60%) probands diagnosed with DSD. We report that AR (n=5) and NR5A1 (n=4) mutations are the commonest cause of 46,XY DSD in Ukraine, accounting for 30% of cases. Other genetic causes of 46, XY DSD included MYRF (n=2), WT1, SRD5A2, HSD17B3, DHX37, AMHR2, KAL and CBX2 variants. In 7 patients (23.3%) we found VUS variants and their causality should be proven in further studies. A multi-disciplinary team has been created for gender assignment in DSD newborns and to improve the decisions of further clinical management, including the time of gonadectomy.
Conclusions: Genomic analysis found a genetic cause in the majority of cases. Further studies to identify novel genes causing DSD are required.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology