Genetic spectrum of disorders of sex development in children in Ukraine

Abstract

Disorders of sex development (DSD) is a group of pathological conditions where there is a discrepancy between the chromosomal, gonadal and phenotypic sex. Objective — to investigate the clinical and molecular genetic characteristics of DSD in children in Ukraine. Materials and methods. We carried out a retrospecti­­ve analysis of 106 medical records of patients with DSD during period from 2000 to 2019 and analyzed the results of clinical data, medical history, hormonal, genetic, functional and instrumental investigations. All patients (from birth to 18 years old) underwent cytogenetic (karyotyping according to the standard methods) and, if necessary, molecular genetic studies (FISH method). Molecular genetic testing was performed in a selected group of patients with 46,XY and 46,XX DSD (n = 49) using whole exome sequencing (WES). Results and discussion. Among the examined 106 patients with DSD, chromosomal DSD was diagnosed in 17.0 % (n = 18) of patients, 46,XY DSD — in 68.9 % (n = 73) and 46,XX DSD — in 14.1 % (n = 15) cases. The majority of children (60 %) out of 46,XY DSD cohort are brought up in a female civilian sex, and 57.1 % of patients out of 46,XX DSD cohort — as males. Among children with 46,XY, and 46,XX DSD genetic testing (WES) found pathogenic mu­­tations in 46.9 % of cases, variants of unknown significan­­ce — in 30.6 % of cases, in 6.1 % of patients the identified mutations were not the cause of DSD, and in 16.3 % of patients WES didn’t find the genetic cause of their disease. According to the data of the Registry, the largest group of DSD in Ukrainian children (68.9 %) is 46,XY DSD, and the most common genetic cause of DSD in them (26 %) are mutations in the androgen receptor gene. Conclusions. All patients with 46,XY and 46,ХХ DSD require genetic testing (in particular WES) to verify the clinical diagnosis, justify treatment tactics and further observation.