Differences in Sex Dev

Question 1

chromosomal variants affecting genitourinary tracts

Answer 1

XO, XXY, Trisomies, mosaicism

Question 2

Mesenchymal cells develop into

Answer 2

genital or gonadal ridges

Question 3

Leydig cells produce _ and are stimulated by _

Answer 3

testosterone, luteinizing hormone

Question 4

Steroli cells produce _ and are stimulated by _

Answer 4

anti mullerian hormone, follicle stimulating hormone

Question 5

Mesonephric ducts give rise to

Answer 5

seminal vesicles, vas deferens, ejaculatory duct, prostate

Question 6

Mullerian ducts give rise to

Answer 6

Fallopian tubes
Uterus
Vagina

Question 7

Primordia are indistinguishable up until week _

Answer 7

12

Question 8

Most common 46, XX DSD

Answer 8

Congenital Adrenal Hyperplasia

Question 9

Cause of congenital adrenal hyperplasia

Answer 9

Gene: CYP21A2; enzyme 21-hydroxylase
Other genes: HSD3B2, CYP11B1, CYP17A1, POR, STAR

Question 10

Phenotype of 46, XX Congenital adrenal hyperplasia

Answer 10

virilized external genitals
US will show uterus and ovaries

Question 11

XY, DSD; X-linked adrenal hypoplasia congenita

Answer 11

Adrenal insufficiency
Mutations in NR0B1 (affect DAX1 protein)
Hypogonadotropic hypogonadism
Undescended testes
Hypospadias

Question 12

46, XY DSD - Androgen insensitivity (aka “Testicular Feminization”) syndrome

Answer 12

X-linked
Complete or partial
Mutations in androgen receptor (AR)
Relatively normal female external genitalia but undescended testes; Mullerian duct regression, so no oviducts, uterus or cervix

Question 13

Kallman syndrome prevalence

Answer 13

1 in 10,000

Question 14

Kallman syndrome genes (X-linked)

Answer 14

KAL1 gene ( also called ANOS1 gene)

Question 15

Kallman syndrome phenotype

Answer 15

Hypogonadotropic hypogonadism
DECREASED SENSE OF SMELL
Can have undescended testes and or hypospadias
Can be associated with other anomalies: CL/CP, Renal agenesis, deafness

Question 16

Campomelic dysplasia GENE

Answer 16

SOX9

Question 17

Campomelic dysplasia phenotype

Answer 17

Macrocephaly
Short, bowed limbs
Dislocated hips
11 pairs of ribs instead of 12
Small chest and lungs
Club feet
Distinctive facial features: small chin, prominent eyes, and a flat face
Cleft palate with a small lower jaw
External genitalia that do not look male or female or normal female genitalia with typical male chromosome pattern

Question 18

Smith Lemli Optiz syndrome gene

Answer 18

DHCR7

Question 19

Smith Lemli Optiz phenotype

Answer 19

Microcephaly
Developmental delay
Cleft palate
Cardiac defects
Fused second and third toes, extra fingers and toes
Underdeveloped external genitals in males

Question 20

WT1- related disorders

Answer 20

Frasier, Denys Drash

Question 21

Frasier syndrome

Answer 21

progressive renal failure and 46,XY complete gonadal dysgenesis
Nucleotides 4-5 of the intron 9 in the WT1 gene (11p13)
Most de novo, autosomal dominant has been reported

Question 22

Denys Dash

Answer 22

XX or XY
Abnormal development of external genitalia in males
90% develop Wilms tumor

Question 23

46, XX male (SRY translocation, duplication of SOX9 or SOX3)

Answer 23

Often have presence of SRY
Male external genitalia ranging from normal to ambiguous
Can have small testes, gynecomastia
Azoospermia
Absence of mullerian structures
Most identify as gender male; would require testosterone supplementation

Question 24

46, XY DSD- Persistent Mullerian Duct Syndrome

Answer 24

Mutations in MIS or the MIS receptor (AMH)
The paramesonephric ducts PERSIST; ie. there is a small uterus and paired fallopian tubes

Question 25

46, XY DSD 5ɑ- reductase deficiency

Answer 25

Mutation in 5ɑ- reductase
External genitalia are partially virilized
Mesonephric ducts are intact

Question 26

Mixed Gonadal dysgenesis - chromosomal mosaicism

Answer 26

Genital difference at birth
Some asymmetry of internal and external anatomy
Gonads are often dysgenetic
Strategy is to wait to categorize patient into phenotype
Tend to be more male phenotype
Hold on reconstructions until reasonably sure

Question 27

Non genetic cause of DSD

Answer 27

Mayer- Rokitansky- Kuster - Hauser syndrome

Question 28

Mayer- Rokitansky- Kuster - Hauser syndrome Phenotype

Answer 28

Accounts for 155 of patients who present with primary amenorrhea
Variable anatomy, most have a vaginal dimple
Can have rudimentary uterine remnants
Normal ovaries and fallopian tubes usually present

Question 29

Kallman genes (AD)

Answer 29

FGFR1, PROKR2, PROK2, CHD7, OR FGF8 genes (causing KS type 2-6; respectively) are autosomal dominant

Question 30

Kallman genes (AR)

Answer 30

PROKR2 and PROK2