OR52-5 Associated Congenital Anomalies in Disorders of Sex Development: Insights from the I-DSD Registry

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: OR52-Reproductive Axis Determination, Development & Transgender Medicine
Tuesday, June 18, 2013: 9:15 AM-10:45 AM
Presentation Start Time: 10:15 AM
Room 104 (Moscone Center)
Kathryn Cox*1, Jillian Bryce1, Jipu Jiang1, Martina Rodie1, Richard Sinnott2, Mona Alkhawari3, Wiebke Arlt4, Antonio Balsamo5, Silvano Bertelloni6, Martine Cools7, Feyza Darendeliler8, Stenvert L Drop9, Mona Ellaithi10, Tulay Guran11, Sven Olaf Hiort12, Paul-Martin Holterhus13, Ieuan Arwel Hughes14, Lidka Lisa15, Yves Morel16, Olle Soder17 and S Faisal Ahmed18
1University of Glasgow, 2University of Melbourne, 3Al- Amiri Hospital, Kuwait, 4University of Birmingham, Birmingham, United Kingdom, 5University of Bologna, 6University of Pisa, 7Univ Hosp Ghent, Ghent, Belgium, 8Istanbul Faculty of Medicine, Istanbul, Turkey, 9Sophia Childrens Hosp, Rotterdam, Netherlands, 10University of Khartoum, Sudan, 11Marmara University Hospital, 12Univ of Luebeck, Luebeck, Germany, 13Univ Hosp Schleswig-Holstein, Kiel, Germany, 14Univ of Cambridge Sch Clin Med, Cambridge, United Kingdom, 152nd Med Schl Charles Univ, Prague, Czech Republic, 16Hopital Debrousse, Lyon Cedex 05, France, 17Karolinska Inst, Stockholm, Sweden, 18Royal Hosp for Sick Children, Glasgow Scotland, United Kingdom
Background: Improved knowledge of the range of anomalies encountered in DSD may improve our understanding of the underlying aetiology. However, given the rarity of these conditions, thorough analysis of congenital anomalies in DSD has not previously been possible.

Aims: To discover the frequency of congenital anomalies in DSD, and to identify patterns of anomalies within specific conditions.

Methods: 1050 registered cases on the I-DSD Registry (UKCRN#12729), currently used by 20 clinical centres in 14 countries, were examined. 649(62%) had consent level to allow sharing suitable information. Case details were obtained from the Registry and where information was unclear the reporting clinician was contacted to obtain further information.

Results: Of 649 cases, congenital anomalies occurred in 173(27%); 107(62%) cases had one anomaly and 66(38%) had two or more anomalies. Commonest anomalies included renal-35(20%), heart-32(18%), skeletal-32(18%), short stature-30(17%), small for gestational age(SGA)-28(16%) and CNS-27(15%). Of the 46XY, 46XX and 45X/46XY cases, anomalies were encountered in 113(25%), 31(26%), 19(45%), respectively. In complete androgen insensitivity syndrome(AIS), congenital anomalies were reported in 8 cases reported to have a mutation in the androgen receptor(AR) gene (ARmut+ve) (range of anomalies: renal, GI tract, heart, skeletal, skin) and in 1 case which was ARmut-ve (renal). Corresponding data for partial AIS: total 10 cases, 2 ARmut+ve, 3 ARmut-ve, 5 unknown. Of 89 cases of non-specific 46XY DSD, associated anomalies were encountered in 43(48%). The range of anomalies included SGA-17(40%), heart-10(23%), CNS-8(19%), renal-7(16%), GI tract-6(14%), ENT-5(12%), skeletal-5(12%), craniofacial-4(9%), short stature-4(9%), eyes-3(7%), respiratory-3(7%), skin-3(7%), adrenal-1(2%), haematological-1(2%), unidentified syndrome-1(2%).

Conclusions: Associated congenital anomalies occur frequently in DSD, including in monogenic conditions such as AIS which are generally thought to solely affect sex development. These findings provide a direction for further study of genetic and environmental causes of DSD.

Nothing to Disclose: KC, JB, JJ, MR, RS, MA, WA, AB, SB, MC, FD, SLD, ME, TG, SOH, PMH, IAH, LL, YM, OS, SFA

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: The International-DSD project is funded by the MRC