ESPE Abstracts

Introduction: Among Disorders of Sex Development (DSDs), XY DSD, represents the most challenging group in terms of identifying a diagnosis.

Objectives: The aim of the study was to determine the prevalence of biochemical and molecular genetic tests in a cohort of boys with XY DSD and to collate the phenotypes of patients with results of laboratory investigations and presence of associated abnormalities.

Methods: New and existing cases of XY DSD who had endocrine and/or genetic evaluation during 2016 and 2017 were identified. Information on clinical assessment including family history, appearance of external genitalia, biochemical and molecular genetic investigations and associated abnormalities was obtained from the medical records.

Results: 52 patients with median age of 0.9 years (range, 0.01, 17.91) and median external masculinization score (EMS) of 9 (2.5, 12) were identified. A positive family history of DSD was present in 10 (19%) children. Of these 52 boys, associated malformations (AM) were found in 27 (52%) with 6 (12%) having a known genetic syndrome. The median EMS of the boys who had associated malformations (AM) was also 9 (2.5, 12). Endocrine assessment revealed an abnormality in 14 (27%) with a median EMS of 8.75 (2.5, 12). The range of endocrine abnormalities consisted of a disorder of gonadal development (DGD) in 10 (19%) and LH deficiency (LHD) in 4 (8%). In the remaining 38 (73%) cases without any endocrine abnormalities who were categorized as a non-specific disorder of under-masculinization (NSDUM) the median EMS was also 9 (3–11). Molecular genetic investigations were completed in 34 (65%) cases and a genetic abnormality was found in 9 (26%). Of the 29 XY DSD boys (NSDUM, 19; DGD, 8; LHD, 2) who had array-CGH, copy number variants (CNVs) were reported in 6 (21%) (NSDUM, 4; DGD, 1; LHD, 1) with a median EMS of 10 (8–11). Sanger sequencing of seven common causative genes in 22 (NSDUM, 16; DGD, 5; LHD, 1) boys identified variants in 3 (14%) (NSDUM, 3) with a median EMS of 3 (3–9) and these were detected in HSD17B3.

Conclusions: The severity of under-masculinization of external genitalia in XY DSD boys seems to be unrelated to the presence of endocrine and array-CGH genetic abnormalities and is not associated with concomitant morbidities. A comprehensive diagnostic strategy that includes a more extended genetic approach requires further exploration.