Endocrine Abstracts

Introduction: Differences/Disorders in Sex Development (DSD) represent a diverse range of conditions that present at various stages of life. A multidisciplinary team (MDT) approach is required to reach a specific diagnosis and management plan, but few large single centre studies of the range and prevalence of diagnoses have been undertaken.

Method: Medical records of all children with DSD discussed at a single MDT between 1-Jan-1996 and 31-Dec-2015 (n=580) were retrospectively reviewed to evaluate the referral patterns and diagnoses; clinical features, biochemical data and genetic analyses were considered.

Results: A total of 271 (1996–2005) and 309 (2006–2015) children were discussed in two respective decades. The relative proportions of DSD categories were similar across two decades (Sex chromosome DSD [SCDSD]: 8.1%/12.0%; 46,XX DSD: 29.2%/25.9%; 46,XY DSD: 62.7%/62.1% in 1996–2005/2006–2015 respectively). Overall, 300/580 children were discussed in their first year of life, with an increase in the number and proportion of children referred earlier in the second decade (2006–2015) (185 versus 115; 59.8% versus 42.4%). Specific diagnoses among children discussed in their first year of life for SCDSD (n=30) included 45,X/46,XY and X variants (n=21), 47,XXY variants and children with 46,XX/46,XY chimerism (n=3). Most children with 46,XX DSD (n=87) had congenital adrenal hyperplasia (CAH) (n=58), the rest having ovotesticular DSD (n=4), isolated clitoromegaly or cloacal anomalies. Among 46,XY DSD (n=183), specific molecular diagnoses were reached in 39 children (including disease-causing variants in SF1, WT1, SOX9, STAR, HSD3B2, HSD17B3, AR, and SRD5A2). Most (n=112) of the others were 46,XY boys with severe hypospadias and often associated features including intra-uterine growth restriction, and/or renal, cardiac or syndromic anomalies. Relatively few 46,XY females presented in infancy (30/109), but molecular diagnosis was reached in 20/23 46,XY females born within the last 10 years.

Conclusion: Children with a heterogeneous range of conditions were referred to the DSD MDT at our centre. Understanding the relative prevalence of those conditions is very valuable. Molecular analysis is useful in reaching a specific diagnosis and directing management, but the underlying pathophysiology in most 46,XY children with severe hypospadias currently remains unknown, and could include genetic, epigenetic, and/or environmental factors.