Disorder of the sex development

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Disorder of the sex development

• A. Luczay

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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
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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
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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
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DISORDERS OF THE EXTERNAL GENITALIA
SINECKER
PRADER
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CLINICAL ASSESSMENTOF INFANTS WITH AMBIGUOUS
GENITALIA
GONADS
PALPABLE
NON-PALPABLE
INCREASED
NORMAL
NORMAL
KARYOTYPE
SERUM Te HIGH LOW
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Classification
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SEX CHROMOSOME DSD DSD KARYOTYPE 46,XY DSD 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

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SEX CHROMOSOME DSD DSD KARYOTYPE 46,XY DSD 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

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SEX CHROMOSOME DSD DSD KARYOTYPE 46,XY DSD 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

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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

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SEX CHROMOSOME DSD DSD KARYOTYPE 46,XY DSD 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

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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

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SEX CHROMOSOME DSD DSD KARYOTYPE 46,XY DSD 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

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Complet gonadal dysgenesisSwyer syndrome

• Bilateral streak gonads
• Apparently normal female external genitalia
• High risk of gonadoblastoma, germinoma
• Karyotype 46,XY

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SEX CHROMOSOME DSD DSD KARYOTYPE 46,XY DSD 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

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Parcial gonadal dysgenesis

• Ambigous genitalia (Leydig cell mass)
• Partial rest of Müllerian duct
• Karyotype 46,XY
• High risk of gonadoblastoma

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SEX CHROMOSOME DSD DSD KARYOTYPE 46,XY DSD 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

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Steroid Hormone Biosynthesis
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17-? hydroxilase defect

• Rare form of CAH
• Both testosterone and estrogen synthesis is
  decreased
• Hypertension, hypokalemia

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SEX CHROMOSOME DSD DSD KARYOTYPE 46,XY DSD 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

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Complete androgen insensitivity

• X q11-12 AR gene
• Female external genitalia, good breast
  development, hairless
• Low risk of gonadoblstoma (2-5)

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SEX CHROMOSOME DSD DSD KARYOTYPE 46,XY DSD 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

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Parcial androgen insensitiviy

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

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SEX CHROMOSOME DSD DSD KARYOTYPE 46,XY DSD 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

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Steroid Hormone Biosynthesis
P450c21
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Cngenital adrenal hyperplasia(21-OHD)

• 1/15000 live birth
• CYP21 gene mutation
• 2/3 salt wasting form

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SEX CHROMOSOME DSD DSD KARYOTYPE 46,XY DSD 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 defect 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

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Treatment
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TS
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KS
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17 ? -OH
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CGD
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CAIS
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21 OH
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PGD
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PAIS