Disorders of Sexual Development

Question 1

What are some teratogens associated with hypospadias?

Answer 1

• rubella virus
• oral contraceptives
• ethanol
• anticonvulsants
• cocaine
• vitamin A

Question 2

What are some teratogens associated with ambiguous genitalia?

Answer 2

• progestational agents
• anticonvulsants

Question 3

What are some teratogens associated with cryptorchidism (undescended testicle)?

Answer 3

• Rubella virus
• Anticonvulsants

Question 4

*review embry

Answer 4

ok

Question 5

What are main 2 types of cells that testis produces?

Answer 5

Leydig + Sertoli cells

Question 6

How does a bipotential gonad develop into a testis?

Answer 6

presence in SRY gene

Question 7

What do Leydig cells produce?

Answer 7

testosterone –> helps dev male reprod structures

Question 8

Who do Sertoli cells produce?

Answer 8

Anti-Mullerian Hormone (AMH)

AKA Mullerian inhibiting substance

leads to regression of Mullerian duct

Question 9

Sertoli cells (that produce AMH) are able to support spermatogenesis how?

Answer 9

• from spermatogonia to spermatid to spermatozoa
• stim by FSH
• secretes androgen binding hormone (ABP) to help concentrate testosterone in lumen of the seminiferous tubule

Question 10

Leydig cells (AKA interstitial cells of Leydig) are located where?

Answer 10

adjacent to seminiferous tubules in testis

Question 11

Leydig cells (AKA interstitial cells of Leydig) are stim by what?

Answer 11

stim by leutinizing hormone (LH) to produce testosterone

contain cholesterol-lipid droplets –> needed for testosterone production

Question 12

What does the Wolffian system include?

Answer 12

• seminal vesicles
• vas deferens
• ejaculatory duct
• prostate

note, men need testosterone to FORM these

Question 13

What do the Mullerian ducts include?

Answer 13

• fallopian tubes
• uterus
• vagina

note, men need AMH to make these fade away

Question 14

What (thinking embry) produces primoridla tissues of external genitalia in both sexes?

Answer 14

proliferation of mesoderm and ectoderm around cloacal membrane

Question 15

Primorida are indistinguishable up until when?

Answer 15

week 12

so all bipotential until 12w

Question 16

What is the most common cause of CAH?

Answer 16

CYP21A2 gene

excessive adrogens from the missing enzyme 21-hydroxylase

Question 17

What would you typically see on US for CAH?

Answer 17

uterus and ovaries

can have variety of external anatomical

Question 18

in the newborn period, CAH can impact ___ levels?

Answer 18

cortisol (and other hormones)

Question 19

What is X-linked adrenal hypoplasia congenita caused by?

Answer 19

mutation of NR0B1 gene –> affects DAX1 protein

Question 20

If you see hypospadias + undescended testicle + adrenal insufficiency –> what do you think?

Answer 20

X-linked adrenal hypoplasia congenita

46,XY

Question 21

What is Androgen Insensitivity Syndrome cause by?

Answer 21

AKA testicular feminization

mutationsin androgen receptor
- X-linked

Question 22

What are the external gen of those w Androgen Insensitivity Syndrome?

Answer 22

since they lack virilization bc androgen receptor not functioning and cannot bind testosterone or DHT –> normal female gen w Undescended testes

Question 23

What are the internal organs of those w Androgen Insensitivity Syndrome?

Answer 23

so they do NOT have uterus or cervix

they DO have external female genitalia + undescended testes

Question 24

What is the X-linked recessive cause of Kallman syndrome?

Answer 24

KAL1

Question 25

What are the AD causes of Kallman syndrome?

Answer 25

FGFR1, PROKR2, PROK2, CHD7 or FGF8 genes (causing KS types 2, 3, 4, 5 and 6, respectively)

Question 26

What are the AR causes of Kallman syndrome?

Answer 26

PROKR2 and PROK2

Question 27

What are the main features assoc w Kallman syndrome?

Answer 27

(can be X-linked, AD, AR) - hypogonadotropic hypogonadism - dec sense of smell - undescended tests and/or hypospadias - other anomalies too

Question 28

What is one organ system you definitely want to check when thinking of DSD?

Answer 28

kidneys

Question 29

What are the DSD implications with Campomelic dysplasia?

Answer 29

so the SOX9 gene causes sex reversal external genitalia not look male or female OR normal female genitalia w typical male chromosome pattern (46,XY)

Question 30

What are the DSD implications in SLO?

Answer 30

(caused by def of enzyme 7-dehydrocholesterol reductase) --> chel metab disorder (DHCR7) underdeveloped external genitalia in males (so not form testicles or ovaries)

Question 31

What is WT1 responsible for?

Answer 31

WT1 --> protein imp in renal and gonadal development WT1-related disorders = Frasier, Denys Drash

Question 32

What is Frasier syndrome?

Answer 32

WT-1 related disorder 46,XY complete gonadal dysgenesis - nuc 4-5 of intron 9 in WT1 gene

Question 33

What is Denys Drash?

Answer 33

WT1-related disorders XX or XY - abnormal devel of external gen in males - 90% have Wilm's tumor

Question 34

What would an SRY translocation OR dup of either SOX9 or SOX3 lead to?

Answer 34

46, XX karyotype --> male so they have XX but also SRY --> leads to male external genitalia from normal --> ambiguous - small testes, gynecomastia - azoospermia - absence of Mullerian structures identifying male need testosterone supplementation

Question 35

What is Persistent Mullerian Duct syndrome?

Answer 35

46,XY Mutation in MIS or AMH (MIS receptor) this leads to the paramesonephric ducts PERSIST, meaning that there is a small uterus + paired fall tubes

Question 36

What is 5a-reductase deficiency?

Answer 36

46, XY mutation in 5a-reductase - so this is needed for converting testos into its more potent androgen DHT (dihydrotestosteron) they have mesonephric ducts (since these only need testos) + normal production of MIS from Sertoli cells --> paramesonephric duct regression

Question 37

Describe mosaic Mixed Gonadal Dysgenesis

Answer 37

chromosomal mosaicism 45,X;46,XY - genital diff at birth w asym of int + ext anatomy - gonads - dysgenetic - wait some time then determine pheno note, more male phenotype = less cancer risk note, used to have surgery right away; now wait

Question 38

What syndrome accounts for 15% patients w primary amenorrhea

Answer 38

Mayer-Rokitansky-Kuster-Hauser syndrome (MRKH) XX - variable anatomy, most w vag dimple - normal ovaries + fall tubes - rudimentary uterine remnants