ESPE Abstracts (2019) 92 P2-272

1National Specialized Children Hospital "OKHMATDYT", Center of Medical Genetics, Kyiv, Ukraine. 2Ukrainian Scientific Center of Endocrine Surgery MOH of Ukraine, pediatric endocrinology department, Kyiv, Ukraine. 3Human Developmental Genetics, Institute Pasteur, Paris, France

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.

Volume 92

58th Annual ESPE

Vienna, Austria
19 Sep 2019 - 21 Sep 2019

European Society for Paediatric Endocrinology 

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