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Flashcards in Disorders of Sex Development Deck (55):
1

46, XX DSD
1. internal genitalia
2. external genitalia
3. fertility
4. gender assignment

1. normal ovaries, uterus
2. virilized
3. potential to bear children
4. female
can be due to exposure of exogenous androgens through mother

2

46, XY DSD
1. internal genitalia
2. external genitalia
3. fertility
4. gender assignment

1. wolffian structures can be normal, hypo plastic, or absent; no mullerian structures
2. under-virilized
3. ?
4. male, exception: complete androgen resistance, completely feminized genitalia, family decision
low: testosterone

3

What are the types of gender reassignment surgeries?
Which is easier to do?

1. reduction of size of phallus, creation of vagina (easier)
2. constructing a phallus

4

steroidogenic factor 1 (SF1)

transcription factor, nuclear receptor: testicular development
development of genital ridge into biopotential gonad
mutation: 46, XY sex reversal or ambiguous genitalia
disease: gonadal and adrenal dysgenesis

5

Wilms tumor 1 (WT1)

transcription factor: testicular development
development of genital ridge into biopotential gonad; also important for KIDNEY
mutation: 46, XY sex reversal or ambiguous genitalia
disease: Frasier syndrome, Denys-Drash syndrome with Wilms tumor

6

LIM1

gene
gonadal development

7

EMX2

gene
gonadal development

8

SRY

Y chromosome
transcription factor: required for differentiation of gonad into testis (absent: gonad becomes ovary)
mutation: gonadal dysgenesis

9

SOX9

transcription factor: testicular development
mutation: campomelic dysplasia, male gonadal dysgenesis or XY sex reveral

10

RSPO1

development of ovary

11

WNT4

development of ovary

12

DAX1

transcriptional regulator, nuclear protein receptor: inhibits gonad from becoming a testis
mutation: gonadal dysgenesis, congenital adrenal hypoplasia

13

AMH/MIS

protein: causes regression of fetal mullein duct, Leydig cell inhibitor
mutation: persistent mullerian duct syndrome

14

StAR

steroidogenic acute regulatory protein: cholesterol into mitochondria
mutant: congenital lipoid adrenal hyperplasia

15

DHH

pro testis

16

AR

androgen receptor transcription factor
mutant: male pseudohermaphrodism, complete or partial androgen insensitivity syndrome

17

AMH/MIS type II receptor

kinase receptor
mutant: persistent mullerian duct syndrome

18

HSD17B3

17B-hydroxysteroid dehydrogenase, 17-ketosteroid reductase
mutant: male pseudohermaphroditism

19

SRD5A2

5a-reductase typer 2
mutant: male pseudohermaphroditism
virilization may occur at puberty

20

CYP17

17-hydroxylase; 20-22-lyase
mutant: male pseudohermaphroditism
low: cortisol
increased deoxycortisone
Sx: HTN, hypokalemia

21

CYP21

21-hydroxylase
mutant: congenital adrenal hyperplasia, female pseudohermaphroditism

22

HSD3B2

3B-hydroxysteroid dehydrogenase type II
mutant: congenital adrenal hyperplasia
can cause 46, XX or 46, XY DSD

23

CYP11B1

11B-hydroxylase
mutant: congenital adrenal hyperplasia

24

FOXL2

development of ovary

25

Leydig cell

secrete: testosterone

26

Sertoli cell

secrete: AMH

27

urogenital sinus

male: prostate gland

28

genital tubercle

male: glans penis
female: clitoris

29

labiourethral folds

male: urethra, ventral shaft of penis
female: labia minora

30

labiosacral folds

male: scrotum
female: labia majora

31

congenital adrenal hyperplasia

MOST COMMON cause of ambiguous genitalia
AR
46, XX DSD
potentially FERTILE
most common defect: 21-hydroxylase deficiency (CYP21); 11-B-hydroxylase deficiency (CYP11B1), 3B-hydroxysteroid dehydrogenase deficiency (HSD3B2 and also a cause of 46, XY DSD)
elevated: 17-hydroxyprogesterone, DHEA, androstenedione, ACTH, PRA (indicates aldosterone deficiency)
low: cortisol
Sx: HTN, areolar hyperpigmentation, dehydration, hyponatremia, hyperkalemia, metabolic acidosis
classic: newborn, salt wasting
Tx: glucocorticoids, fludrocortisone

32

testosterone biosynthetic defects

AR
46, XY DSD
HCG stimulation: low testosterone and DHT

33

Leydig cell hypoplasia

AR
46, XY DSD
HCG stimulation: low testosterone and DHT

34

5a-reductase deficiency

AR
46, XY DSD
mutation: SRD5A2
elevated: testoterone/DHT ratio (after HCG stimulation)
puberty: virilization occurs in many
skin fibroblast culture for 5a-reductase deficiency

35

androgen insensitive syndrome

X linked
46, XY DSD
mutation: AR
elevated: AMH
normal: testosterone levels with normal rise with HCG stimulation
risk: gonadoblastoma

36

gonadal dysgenesis (Swyer syndrome)

sporadic and familial
sex chromosome DSD
mutation: SRY (most it is intact)
elevated: gonadotropins
low: AMH
HCG stimulation: low testosterone and DHT
risk: germ cell tumor
complete: phenotypic females (not ambiguous)
Sx: amenorrhea at puberty

37

ovotesticular DSD
1. internal genitalia
2. external genitalia
3. fertility
4. gender assignment

sporadic and familial
most: 46, XX; also sex chromosome DSD
1. both testicular and ovarian tissue, most uterus
2. usually ambiguous; can have normal male or female
3. ?
4. depends on external/internal genitalia (many develop gynecomastia and menstruate)
risk: gonadoblastoma

38

What should the penile length be of a full-term newborn?

greater than 2.5 cm

39

anogenital ratio

AF/AC

AF: distance from the anus to the fourchette
AC: distance from the anus to the base of the clitoris

anogenital ratio greater than 0.5: fusion of labioscrotal folds (virilization)

normal full term phallus: 2.5 cm

40

sex chromosome DSD
1. internal genitalia
2. external genitalia
3. fertility
4. gender assignment

karyotype is not typical 46, XX or 46, XY
1. one dysgenic testis, one streak gonad, no ovarian tissue
2. ambiguous
3. ?
4. MGD: most female

41

mixed gonadal dysgenesis (partial gonadal dysgenesis)

45,X/46,XY
sex chromosome DSD
ambiguous asymmetrical external genitalia: enlarged labioscrotal fold on side with testis
risk: germ cell tumor

42

chimerism

46,XX/46,XY
sex chromosome DSD

43

Turner syndrome

45,X
sex chromosome DSD with un-ambigious genitalia

44

Klinefelter syndrome

47,XXY
sex chromosome DSD with un-ambigious genitalia

45

aromatase deficiency

46, XX DSD

46

disorders of androgen synthesis or action
1. internal genitalia
2. external genitalia
3. fertility
4. gender assignment

46, XY DSD
1. testes in abdomen
2. female
3. ?
4. ?
mutations: StAR, CYP11A
low: testosterone
elevated: LH
HCG stimulation: no rise in testosterone

47

congenital lipoid adrenal hyperplasia

46, XY DSD
mutation: StAR, CYP11A
no steroid hormones are made, severe salt wasting
often fatal

48

CYP11A

cholesterol side chain cleavage enzyme
mutation: congenital lipoid adrenal hyperplasia

49

3B-hydroxysteroid dehydrogenase deficiency

46, XY DSD
mutation: HSD3B2
low: cortisol
increased deoxycortisone
Sx: HTN, hypokalemia

50

17B-hydroxysteroid dehydrogenase or 17-ketosteroid reductase deficiency

46, XY DSD
mutation: HSD17B3
NO signs of CAH
HCG stimulation: low testosterone, DHT

51

persistent mullerian duct syndrome

46, XY
NO ambiguous genitalia
mutation: AMH or AMHRII
Sx: cryptorchidism, hernia uteri inguinale
few are fertile, high incidence of postnatal testicular degeneration

52

congential anorchia

testes function at least until 16 week of gestation then disappeared
elevated: LH, FSH
low: testosterone, AMH
Tx: testosterone therapy at puberty

53

Denys Drash syndrome

WT1 mutation
nephropathy, wilms tumor, genital abnormalities

54

Frasier syndrome

WT1 mutation
normal external female genitalia with XY karyotype
streak gonads that often develop into gonadoblastoma
nephrotic syndrome

55

Smith-Lemli Optiz

mutaiton in 7-dehydrocholesterol reductase leading to increase in 7-dehydrocycholesteol
look female
XY: undervirilized