Presentation is loading. Please wait.

Presentation is loading. Please wait.

Disorder of the sex development A. Luczay. Sex development GENETIC X X X Y (chromosal) GONADAL ovarium testis GENITAL INTERNAL uterus prostate EXTERNAL.

Similar presentations


Presentation on theme: "Disorder of the sex development A. Luczay. Sex development GENETIC X X X Y (chromosal) GONADAL ovarium testis GENITAL INTERNAL uterus prostate EXTERNAL."— Presentation transcript:

1 Disorder of the sex development A. Luczay

2 Sex development GENETIC X X X Y (chromosal) GONADAL ovarium testis GENITAL INTERNAL uterus prostate EXTERNAL female male SEX ASSIGNMENT girl boy PSYCHOSOCIAL female male

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

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

5 DISORDERS OF THE EXTERNAL GENITALIA PRADER SINECKER

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

7 Classification

8 SEX CHROMOSOME DSDDSD KARYOTYPE : 46,XYDSD KARYOTYPE: 46,XX Disorder of testicular development Disorder of ovarian development 45,X Turner syndrome 1. Complet Gonadal Dysgenesis (Swyer syndroma) 1. Ovotesticular DSD 2. Partial Gonadal Dysgenesis 2. testis SRY+, SOX9 duplication 3. Testicular regression 3. gonadal dysgenesis 4. Ovotesticular DSD 47, XXY Klinefelter syndrome Defect in androgen biosynthesis or in androgen action Androgen over production 1. defect in biosynthesis (17  hydroxilase defect, 17  HSD, 5  reductase defect, Star mutation) 1. fetal origin: 21-OH def./11  OH def. 2. fetoplacental origin aromatase defektus 3. maternal origin: luteoma, exogén 2. defect in action (CAIS, PAIS) 45X/46,XY Mixed gonadal dysgenesis (ovotesticular DSD) 46,XX/46,XY Chimeric ovotesticular DSD 3. LH receptor mutation (Leydig-hypoplasia, aplasia) 4. Persistent Müllerian duct syndrome

9 SEX CHROMOSOME DSDDSD KARYOTYPE : 46,XYDSD KARYOTYPE: 46,XX Disorder of testicular development Disorder of ovarian development 45,X Turner syndrome 1. Complet Gonadal Dysgenesis (Swyer syndroma) 1. Ovotesticular DSD 2. Partial Gonadal Dysgenesis 2. testis SRY+, SOX9 duplication 3. Testicular regression 3. gonadal dysgenesis 4. Ovotesticular DSD 47, XXY Klinefelter syndrome Defect in androgen biosynthesis or in androgen action Androgen over production 1. defect in biosynthesis (17  hydroxilase defect, 17  HSD, 5  reductase defect, Star mutation) 1. fetal origin: 21-OH def./11  OH def. 2. fetoplacental origin aromatase defektus 3. maternal origin: luteoma, exogén 2. defect in action (CAIS, PAIS) 45X/46,XY Mixed gonadal dysgenesis (ovoteticular DSD) 46,XX/46,XY Chimeric ovotesticular DSD 3. LH receptor mutation (Leydig-hypoplasia, aplasia) 4. Persistent Müllerian duct syndrome

10 SEX CHROMOSOME DSDDSD KARYOTYPE : 46,XYDSD KARYOTYPE: 46,XX Disorder of testicular development Disorder of ovarian development 45,X Turner syndrome 1. Complet Gonadal Dysgenesis (Swyer syndroma) 1. Ovotesticular DSD 2. Partial Gonadal Dysgenesis 2. testis SRY+, SOX9 duplication 3. Testicular regression 3. gonadal dysgenesis 4. Ovotesticular DSD 47, XXY Klinefelter syndrome Defect in androgen biosynthesis or in androgen action Androgen over production 1. defect in biosynthesis (17  hydroxilase defect, 17  HSD, 5  reductase defect, Star mutation) 1. fetal origin: 21-OH def./11  OH def. 2. fetoplacental origin aromatase defektus 3. maternal origin: luteoma, exogén 2. defect in action (CAIS, PAIS) 45X/46,XY Mixed gonadal dysgenesis (ovoteticular DSD) 46,XX/46,XY Chimeric ovotesticular DSD 3. LH receptor mutation (Leydig-hypoplasia, aplasia) 4. Persistent Müllerian duct syndrome

11

12

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

14 SEX CHROMOSOME DSDDSD KARYOTYPE : 46,XYDSD KARYOTYPE: 46,XX Disorder of testicular development Disorder of ovarian development 45,X Turner syndrome 1. Complet Gonadal Dysgenesis (Swyer syndroma) 1. Ovotesticular DSD 2. Partial Gonadal Dysgenesis 2. testis SRY+, SOX9 duplication 3. Testicular regression 3. gonadal dysgenesis 4. Ovotesticular DSD 47, XXY Klinefelter syndrome Defect in androgen biosynthesis or in androgen action Androgen over production 1. defect in biosynthesis (17  hydroxilase defect, 17  HSD, 5  reductase defect, Star mutation) 1. fetal origin: 21-OH def./11  OH def. 2. fetoplacental origin aromatase defektus 3. maternal origin: luteoma, exogén 2. defect in action (CAIS, PAIS) 45X/46,XY Mixed gonadal dysgenesis (ovotesticular DSD) 46,XX/46,XY Chimeric ovotesticular DSD 3. LH receptor mutation (Leydig-hypoplasia, aplasia) 4. Persistent Müllerian duct syndrome

15

16

17

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

19 SEX CHROMOSOME DSDDSD KARYOTYPE : 46,XYDSD KARYOTYPE: 46,XX Disorder of testicular development Disorder of ovarian development 45,X Turner syndrome 1. Complet Gonadal Dysgenesis (Swyer syndroma) 1. Ovotesticular DSD 2. Partial Gonadal Dysgenesis 2. testis SRY+, SOX9 duplication 3. Testicular regression 3. gonadal dysgenesis 4. Ovotesticular DSD 47, XXY Klinefelter syndrome Defect in androgen biosynthesis or in androgen action Androgen over production 1. defect in biosynthesis (17  hydroxilase defect, 17  HSD, 5  reductase defect, Star mutation) 1. fetal origin: 21-OH def./11  OH def. 2. fetoplacental origin aromatase defektus 3. maternal origin: luteoma, exogén 2. defect in action (CAIS, PAIS) 45X/46,XY Mixed gonadal dysgenesis (ovotesticular DSD) 46,XX/46,XY Chimeric ovotesticular DSD 3. LH receptor mutation (Leydig-hypoplasia, aplasia) 4. Persistent Müllerian duct syndrome

20

21 Complet gonadal dysgenesis Swyer syndrome  Bilateral streak gonads  Apparently normal female external genitalia  High risk of gonadoblastoma, germinoma  Karyotype: 46,XY

22 SEX CHROMOSOME DSDDSD KARYOTYPE : 46,XYDSD KARYOTYPE: 46,XX Disorder of testicular development Disorder of ovarian development 45,X Turner syndrome 1. Complet Gonadal Dysgenesis (Swyer syndroma) 1. Ovotesticular DSD 2. Partial Gonadal Dysgenesis 2. testis SRY+, SOX9 duplication 3. Testicular regression 3. gonadal dysgenesis 4. Ovotesticular DSD 47, XXY Klinefelter syndrome Defect in androgen biosynthesis or in androgen action Androgen over production 1. defect in biosynthesis (17  hydroxilase defect, 17  HSD, 5  reductase defect, Star mutation) 1. fetal origin: 21-OH def./11  OH def. 2. fetoplacental origin aromatase defektus 3. maternal origin: luteoma, exogén 2. defect in action (CAIS, PAIS) 45X/46,XY Mixed gonadal dysgenesis (ovotesticular DSD) 46,XX/46,XY Chimeric ovotesticular DSD 3. LH receptor mutation (Leydig-hypoplasia, aplasia) 4. Persistent Müllerian duct syndrome

23

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

25 SEX CHROMOSOME DSDDSD KARYOTYPE : 46,XYDSD KARYOTYPE: 46,XX Disorder of testicular development Disorder of ovarian development 45,X Turner syndrome 1. Complet Gonadal Dysgenesis (Swyer syndroma) 1. Ovotesticular DSD 2. Partial Gonadal Dysgenesis 2. testis SRY+, SOX9 duplication 3. Testicular regression 3. gonadal dysgenesis 4. Ovotesticular DSD 47, XXY Klinefelter syndrome Defect in androgen biosynthesis or in androgen action Androgen over production 1. defect in biosynthesis (17  hydroxilase defect, 17  HSD, 5  reductase defect, Star mutation) 1. fetal origin: 21-OH def./11  OH def. 2. fetoplacental origin aromatase defektus 3. maternal origin: luteoma, exogén 2. defect in action (CAIS, PAIS) 45X/46,XY Mixed gonadal dysgenesis (ovoteticular DSD) 46,XX/46,XY Chimeric ovotesticular DSD 3. LH receptor mutation (Leydig-hypoplasia, aplasia) 4. Persistent Müllerian duct syndrome

26

27 Steroid Hormone Biosynthesis dehidroepiandrosterone HO O O O 17  -OH-progesterone cholesterol ALDOSTERONE Pregnenolone Progesterone 11-Dezoxycortisol Corticosterone CORTIZOL 17  OH-pregnenolone C HO CH 3 O C O O DOC C O CH 2 OH O C O O HO O C CH 2 OH O HO OCH OH C HO CH 3 O OH C O CH 3 O OH C O CH 2 OH O HO C O CH 2 OH O OH 17 ANDROSTENEDIONE

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

29 SEX CHROMOSOME DSDDSD KARYOTYPE : 46,XYDSD KARYOTYPE: 46,XX Disorder of testicular development Disorder of ovarian development 45,X Turner syndrome 1. Complet Gonadal Dysgenesis (Swyer syndroma) 1. Ovotesticular DSD 2. Partial Gonadal Dysgenesis 2. testis SRY+, SOX9 duplication 3. Testicular regression 3. gonadal dysgenesis 4. Ovotesticular DSD 47, XXY Klinefelter syndrome Defect in androgen biosynthesis or in androgen action Androgen over production 1. defect in biosynthesis (17  hydroxilase defect, 17  HSD, 5  reductase defect, Star mutation) 1. fetal origin: 21-OH def./11  OH def. 2. fetoplacental origin aromatase defektus 3. maternal origin: luteoma, exogén 2. defect in action (CAIS, PAIS) 45X/46,XY Mixed gonadal dysgenesis (ovoteticular DSD) 46,XX/46,XY Chimeric ovotesticular DSD 3. LH receptor mutation (Leydig-hypoplasia, aplasia) 4. Persistent Müllerian duct syndrome

30

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

32 SEX CHROMOSOME DSDDSD KARYOTYPE : 46,XYDSD KARYOTYPE: 46,XX Disorder of testicular development Disorder of ovarian development 45,X Turner syndrome 1. Complet Gonadal Dysgenesis (Swyer syndroma) 1. Ovotesticular DSD 2. Partial Gonadal Dysgenesis 2. testis SRY+, SOX9 duplication 3. Testicular regression 3. gonadal dysgenesis 4. Ovotesticular DSD 47, XXY Klinefelter syndrome Defect in androgen biosynthesis or in androgen action Androgen over production 1. defect in biosynthesis (17  hydroxilase defect, 17  HSD, 5  reductase defect, Star mutation) 1. fetal origin: 21-OH def./11  OH def. 2. fetoplacental origin aromatase defektus 3. maternal origin: luteoma, exogén 2. defect in action (CAIS, PAIS) 45X/46,XY Mixed gonadal dysgenesis (ovoteticular DSD) 46,XX/46,XY Chimeric ovotesticular DSD 3. LH receptor mutation (Leydig-hypoplasia, aplasia) 4. Persistent Müllerian duct syndrome

33

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

35 SEX CHROMOSOME DSDDSD KARYOTYPE : 46,XYDSD KARYOTYPE: 46,XX Disorder of testicular development Disorder of ovarian development 45,X Turner syndrome 1. Complet Gonadal Dysgenesis (Swyer syndroma) 1. Ovotesticular DSD 2. Partial Gonadal Dysgenesis 2. testis SRY+, SOX9 duplication 3. Testicular regression 3. gonadal dysgenesis 4. Ovotesticular DSD 47, XXY Klinefelter syndrome Defect in androgen biosynthesis or in androgen action Androgen over production 1. defect in biosynthesis (17  hydroxilase defect, 17  HSD, 5  reductase defect, Star mutation) 1. fetal origin: 21-OH def./11  OH def. 2. fetoplacental origin aromatase defektus 3. maternal origin: luteoma, exogén 2. defect in action (CAIS, PAIS) 45X/46,XY Mixed gonadal dysgenesis (ovoteticular DSD) 46,XX/46,XY Chimeric ovotesticular DSD 3. LH receptor mutation (Leydig-hypoplasia, aplasia) 4. Persistent Müllerian duct syndrome

36

37 Steroid Hormone Biosynthesis dehidroepiandrosterone HO O O O 17  -OH-progesterone cholesterol ALDOSTERONE Pregnenolone Progesterone 11-Dezoxycortisol Corticosterone CORTIZOL 17  OH-pregnenolone C HO CH 3 O C O O DOC C O CH 2 OH O C O O HO O C CH 2 OH O HO OCH OH C HO CH 3 O OH C O CH 3 O OH C O CH 2 OH O HO C O CH 2 OH O OH 17 ANDROSTENEDIONE P450 c21

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

39 SEX CHROMOSOME DSDDSD KARYOTYPE : 46,XYDSD KARYOTYPE: 46,XX Disorder of testicular development Disorder of ovarian development 45,X Turner syndrome 1. Complet Gonadal Dysgenesis (Swyer syndroma) 1. Ovotesticular DSD 2. Partial Gonadal Dysgenesis 2. testis SRY+, SOX9 duplication 3. Testicular regression 3. gonadal dysgenesis 4. Ovotesticular DSD 47, XXY Klinefelter syndrome Defect in androgen biosynthesis or in androgen action Androgen overproduction 1. defect in biosynthesis (17  hydroxilase defect, 17  HSD, 5  reductase defect, Star mutation) 1. fetal origin: 21-OH def./11  OH def. 2. fetoplacental origin aromatase defe ct 3. maternal origin: luteoma, exogén 2. defect in action (CAIS, PAIS) 45X/46,XY Mixed gonadal dysgenesis (ovoteticular DSD) 46,XX/46,XY Chimeric ovotesticular DSD 3. LH receptor mutation (Leydig-hypoplasia, aplasia) 4. Persistent Müllerian duct syndrome

40

41 Treatment

42 TS

43

44 KS

45 17  -OH

46 CGD

47 CAIS

48 21 OH

49 PGD

50 PAIS


Download ppt "Disorder of the sex development A. Luczay. Sex development GENETIC X X X Y (chromosal) GONADAL ovarium testis GENITAL INTERNAL uterus prostate EXTERNAL."

Similar presentations


Ads by Google