Introduction: Evaluation of XY DSD requires a combination of endocrine and genetic tests. It is unclear whether these two sets of investigations should be performed stepwise or in parallel.
Aims: The aim of the study was to document the range of endocrine and genetic abnormalities identified in all XY boys who were investigated at one specialist multidisciplinary service.
Methods: Case records were reviewed to collect information from all 46,XY boys who presented for evaluation of atypical genitalia in Glasgow between 2010 and 2015. Detailed phenotypic information including external masculinisation score (EMS), biochemical and genetic diagnosis was studied.
Results: boys with median EMS of 9 (range 1,11) were included. Associated malformations (AM) were present in 39 (32%) with 14 (11%) having a recognisable syndrome. The median EMS of those with or without AM was the same at 9 (1,11). A family history of DSD was present in 16 (13%) and consanguinity in 3 (2%). An endocrine abnormality of gonadal function was present in 28 (23%) with a median EMS of 8.3 (1,10.5). These abnormalities included a disorder of gonadal development (DGD) in 19 (15%), LH deficiency (LHD) in 5 (4%) and a disorder of androgen synthesis (DAS) in 4 (3%). In the remainder, there were 91 (75%) cases of non-specific disorder of undermasculinisation (NSDUM), 2 (2%) cases of disorder of Müllerian development (DMD) and one case (1%) of cloacal anomaly. Of 43 cases (NSDUM, 30; DGD, 10; LHD, 3) who had array-CGH, copy number variants (CNVs) were reported in 13 (30%) (NSDUM,9; DGD, 4) with a median EMS of 8.5 (1.5,11). Limited gene panel analysis in 61 (NSDUM,41; DGD,15; DAS,2; DMD,2; Cloacal Anomaly,1) identified variants in 6 (10%) (NSDUM,3; DGD,1; DAS;2) with a median EMS of 6 (3,9). CNVs were detected more frequently in cases that had associated malformations (P=0.03).
Conclusions: In boys with suspected XY DSD, the likelihood of identifying an abnormal diagnostic test seems to be unrelated to the appearance of the external genitalia. In addition, there is no association between a genetic and endocrine abnormality. A parallel genetic and endocrine approach for evaluating DSD needs further consideration.
23 - 25 Nov 2016
British Society for Paediatric Endocrinology and Diabetes