Challenges in Disorders of Sex Development (DSD ) What Specialized Centers,

1. Challenges in Disorders of Sex Development (DSD) What Specialized Centers, Societies and Networks Can Provide Hüseyin ÖZBEY Department of PediatricSurgery Division of PediatricUrology IstanbulMedicalFaculty IstanbulUniversity www.dsdturk.org

2. TERMINOLOGY “HERMAPHRODITISM”“AMBIGUOUS GENITALIA”“INTERSEX”“DISORDERS OF SEX DEVELOPMENT” (DSD)“DIFFERENCES OF SEX DEVELOPMENT” (DSD)

3. Disorders of SexDevelopment(DSD) Congenitalconditionswith a mismatch of; genetic, gonadal, anatomical, psychologicalSEX “ATYPICAL SEX”

4. Sexualdifference Themostcharacteristicdifference of HUMAN BODY externalgenitalia

5. Sexualdifference • Themostcharacteristicdifference of HUMAN BEHAVIOR genderidentity & sexualorientation affectedbythe externalgenitalia! One in 300 - 4500 infants is bornwithabnormalities of theexternalgenitalia

6. DSD • DIFFERENCES OF SEXUAL DEVELOPMENT • wide rangeofvariations from the statistically normal • DISORDERS OF SEXUAL DEVELOPMENT • needmedical/surgicalintervention • XY-DSD • XX-DSD • Ovotesticular-DSD • XX-male • XY-female (gonadaldysgenesis)

7. M. Caster SEMENYA (born 7 January 1991) • South African runner and world champion • Won gold in 800 metres at the 2009 World Championships • Subjected to "gender testing“ • Underwentgenderverification

8. Erik Schinegger(born19June 1948) • Austrianskier and worldchampion in 1966 • raised as female (Erika Schinegger) • subjectedto “gendertesting” • diagnosed as XY • wentundergender re-assignment & married, became a father

9. Now, his name is İsmail (25)Hürriyet, December 30, 2009 Satiye’sfightformaleness (26) (Milliyet, September 4, 2005)

10. Examples of externalgenitaliain patientswith DSD CAH-E.K. CAH

11. Examples of externalgenitaliain patientswith DSD CAH-B.T. 5AR-D.A.

12. Examples of externalgenitaliain patientswith DSD XX-male, M.G. 17BHSD-G.L.

13. Examples of internal & externalgenitaliain patientswith DSD CAIS-C.E. Crossedtesticularectopia&PMD-A.A.G

14. Sexual & behavioraldifferentiation • Biologicsex • chromosomes & genes & gonadalhistology • hormones & enzymes & factors & receptors • Gender • Genderidentity • (pre-postnatalhormonaleffects; how a personviewsoneself as male (man) orfemale (woman), or (DSD) • Gender role - behavior - orientation (play, wear, job, sports, physicalagressionetc; how a person is viewedbyothermembers of society as masculineorfeminine, and theireroticbehavior)

15. Genetic & Gonadalsexdetermination • Sex determining genes on the sex chromosomes • SRY - Yp11.3 • DAX1 - Xp21.3 • Sexdetermining genes on the autosomes • SOX9- 17q24 • DMRT1 - 9p24.3 • SF1 - 9q33 • WT1 - 11p13 • Wnt4 - 1p35 More genes to be identified... to date, in abouthalf of allpatientswith DSD can be genetically explained!

16. Problemswith DSD • Sex of rearing • Metabolicconditions • Sexualfunction • Fertility • Risk of tumordevelopment • Genderpanic! • Genderpanic: • thefear of the “possibility of homosexuality” bytheparents of childrenwith “ambiguousgenitalia”!

17. DSD management • Experienced & consultingmultidisciplinaryteam(endocrinology, psychiatry&psychology, genetics, radiology, surgery) • Laboratory • (chromosomalanalysis, SRY, moleculargenetics, hormones, MIF, inhibin-B, radiology, surgery, pathology) • Follow-up and goodcommunication • (byeachspecialist)

18. DSD Surgery • EARLY (withinthefirstyear) • LATE (afterpuberty)

19. Goals of DSD surgery • esthetic and gender-typicalappearance • un-obstructedurinary emptying without incontinence or infections • good adult sexual and reproductive function

20. DSD Surgerymajor (sacrifying) / minor (normalising) masculinizingfeminizing orchidopexy urethroplasty removal of Müllerianducts gonadectomy clitoroplasty vaginoplasty • impaired body - genitalimage • emotionaltrauma & ego loss • infertility

21. Urethroplasty (hypospadias) preoperativepostoperative

22. Urethroplasty (hypospadias) preoperativepostoperative

23. Urethroplasty (hypospadias) preoperative postoperative

24. Urethroplasty & MD removal XX-male M.G. postoperative preoperative

25. Clitoroplasty & gonadectomy 17BHSD-G.L. preoperative postoperative

26. Gonadectomy PAIS-

27. Clitoro-vaginoplasty (CAH) preoperative postoperative

28. Informedconsentforsurgery Do parentshavetheauthoritytoconsent togenitalnormalizing and sexassignmentsurgery on behalf of theirinfants? theonlypersonwithoutconsent is thepatienthimselforherself! Ethical ! ? Legal !?

30. Diagnostic and longtermtreatmentproblems in DSD • Uniquechallenge! • Definition of theillness/situation • Smallsamplesizes • Lack of laboratorystudies & experiencedresearcher • Lack of accuratediagnosis • Genetic, clinical, neurological, psychosocial • Lack of experiencedsurgeon • Fertilityissues

31. Clinicalproblems in DSD • Lack of experiencedcareprovider! • a differentphysician & newdiagnosis • additional and/orunnecessarylaboratoryanalyses • increasedparentaldistress LIMITED TIME FOR CLINICAL AND LABORATORY EVALUATION DELAYED GENDER ASSIGNMENT!

32. Clinicalproblems in DSD • non-educatedparents ! • Disclosure of diagnosis • needsstrictconfidence • Decisionmakingprocess • (child) & familyconcerns • informedconsent • psycosocialinquiry • someparentsconsult and getinformed • someparentsjustletthesituation be as doctors’ wishes

33. Decision-making& therapy-planningprocess • Multidisciplinaryhealth-careteam • Goodcommunication & collaboration • Eachcasemust be consideredindividually! Parentsmusthave understoodthe plannedinterventions, their significance

34. Culturaleffects in DSD Attitudes towards sex of rearing in late (&early!) diagnosedpatients with DSD in Eastern countriesarevery different fromthose in Western countries!

35. 46,XX “male” - CAH

36. It is extremelydifficulttocorrectthegender of patientswith f-CAH whentheypresent at >2.5 years of ageGenderassignment in femalecongenital adrenal hyperplasia: a difficultexperienceÖzbey H, et al BJU Int. 2004 Aug;94(3):388-91

37. maleoffspring • traditionalbreadwinner • responsibleforparentalcare • carriesfamilyproperty (consanguinousmarriage!) • fear of socialridicule • Ineasterncountries, cultural, economic and social factors • are moreimportant than sexual potential!

38. DSD Societies& SupportGroups www.isna.org www.ukia.co.uk www.xy-frauen.de AGS-Eltern- undPatienteninitiative e.V. www.ags-initiative.de www.bodieslikeours.org AISSG: AndrogenInsensitivitySupportGroupwww.aissg.org www.heainfo.org www.sindromedimorris.org

39. DSD Societies& SupportGroups

40. Supportgroups Lübeck 2011

41. Supportgroups London 2011

42. DSD Networks www.orpha.net www.eurocat-network.eu www.eurodsd.eu www.netzwerk-is.de

43. EuroDSD - consortium BHAM - TheUniversity of Birmingham CAU-Christian-Albrechts-UniversitätzuKiel EUR- ErasmusUniversitairMedischCentrum, Rotterdam GABO:mi- GABO:milliariummbH & Co. KG, München HCL-HospicesCivils de Lyon IPP-InstitutPasteur, Paris KI- KarolinskaInstitutet, Stockholm UCAM PAED - University of Cambridge UCL-UniversityCollegeLondon UNIPI- University of Pisa UOG- University of Glasgow UZL - UniversitätzuLübeck WWU Muenster

44. EuroDSD

45. What Specialized Centers, Societies and Networks Can Provide ? • National & International • Clinical - Research Networks & Experts • Collaborationwithsharing • Data • Information • Experience

46. What Specialized Centers, Societies and Networks Can Provide ? • rapidclinical & laboratoryevaluation • earlydiagnosis • peer support ends isolation and stigmatization • increasedexperience & qualitycare • helptofind the best quality care

47. INTERSEXOne-daySymposiumMay 1, 2006Istanbul www.dsdturk.org MiltonDiamond, Professor University of Hawaii, John A BurnsSchool of Medicine PacificCenterforSex and Society Honolulu, Hawaii, USA Heino FL Meyer-Bahlburg, Professor NY StatePsychiatricInstitute Columbia University, New York, USA

48. dsdturk www.dsdturk.org Cinsel Gelişim ve Hipospadiyas Derneği SexualDevelopment and HypospadiasAssociation