Disorder of the sex development Rickets

1. Disorder of the sex developmentRickets A. Luczay

2. Sex development GENETIC X XX Y (chromosal) GONADAL ovariumtestis GENITAL INTERNAL uterusprostate EXTERNAL femalemale SEX ASSIGNMENT girl boy PSYCHOSOCIAL female male

3. DIFFERENTIATIONOF THE GONADS PRIMORDIAL GERM CELS ADRENAL MEDULLA ADRENAL CORTEX WOLFFIAN DUCT MÜLLERIAN DUCT MEDULLA CORTEX BIPOTENTIAL GONAD 46 XX 46 XY DEVELOPING TESTIS DEVELOPING OVARY TUBULUBI SEMINIFERIS WOLFFIAN DEGENERATION PRIMARY FOLLICLES CONDUCTING DUCT SPERMATO- GONIUMS MÜLLERIAN DUCT REGRESSION FALLOPIAN TUBE

4. GENITAL DIFFERENTIATION INDIFFERENT STAGE INDIFFERENT STAGE GONAD MESONEPHROS MÜLLERIAN DUCT WOLFFIAN DUCT UROGENITAL FOLD LABIOSCROTAL SWELLING MALE FEMALE GLANS UROGENI- TAL FOLD FUSIONED UROGENITAL FOLD URETH-RAL SLIT EPIDIDYMIS OVARY TESTIS FALLO-PIAN TUBE ANUS VAS DEFERENS GLANS PENIS URETHRAL MEATUS CLITORIS SEMINAL VESICLE UTERUS VAGINAL ORIFICE PROSTATE RAPHE VAGINA FEMALE MALE

5. DISORDERS OF THE EXTERNAL GENITALIA SINECKER PRADER

6. CLINICAL ASSESSMENTOF INFANTS WITH AMBIGUOUS GENITALIA GONADS PALPABLE NON-PALPABLE INCREASED NORMAL NORMAL KARYOTYPE SERUM Te HIGH LOW

7. Classification

13. Turner syndrome • 1/2500 live female birth • Hand-food edema in infancy • Pterygium colli (neck webbing), Low posterior hairline, Broad chest, short stature • Cardiac, renal malformations • Karyotype: 45,X

18. Klinefelter syndrome • 1/500-1000 live male birth • Small testis, high stature, learning difficulties, gynecomastia in puberty • At pubert testicular size increases (~10 ml) Midpuberty: low androgen level • Karyotype: 47,XXY

21. Complet gonadal dysgenesisSwyer syndrome • Bilateral streak gonads • Apparently normal female external genitalia • High risk of gonadoblastoma, germinoma • Karyotype: 46,XY

24. Parcial gonadal dysgenesis • Ambigous genitalia (Leydig cell mass) • Partial rest of Müllerian duct • Karyotype: 46,XY • High risk of gonadoblastoma

27. CH3 C O O CH2OH CH2OH CH2OH CH2OH C C C C O O O O O O O O CH2OH C O cholesterol CH3 CH3 O C C O O OH 17 HO HO dehidroepiandrosterone HO Pregnenolone 17a-OH-pregnenolone CH3 O C O OH O O 17a-OH-progesterone Progesterone ANDROSTENEDIONE OH DOC 11-Dezoxycortisol HO HO OH Corticosterone CORTIZOL OCH HO O ALDOSTERONE Steroid Hormone Biosynthesis

28. 17- hydroxilase defect • Rare form of CAH • Both testosterone and estrogen synthesis is decreased • Hypertension, hypokalemia

31. Complete androgen insensitivity • X q11-12 – AR gene • Female external genitalia, good breast development, hairless • Low risk of gonadoblstoma (2-5%)

34. Parcial androgen insensitiviy • X q11-12 • The seerity of undervirilisation depend on the receptor sensitivity. • High risk of gonadoblastoma

37. CH3 C O O CH2OH CH2OH CH2OH CH2OH C C C C O O O O O O O O CH2OH C O cholesterol CH3 CH3 O C C O O OH 17 HO HO dehidroepiandrosterone HO Pregnenolone 17a-OH-pregnenolone CH3 O C O OH O O 17a-OH-progesterone Progesterone ANDROSTENEDIONE OH DOC 11-Dezoxycortisol HO HO OH Corticosterone CORTIZOL OCH HO O ALDOSTERONE Steroid Hormone Biosynthesis P450c21

38. Cngenital adrenal hyperplasia(21-OHD) • 1/15000 live birth • CYP21 gene mutation • 2/3 salt wasting form

41. Treatment

42. TS

44. KS

45. 17  -OH

46. CGD

47. CAIS

48. 21 OH

49. PGD

50. PAIS