Differences in Sex Dev Flashcards
chromosomal variants affecting genitourinary tracts
XO, XXY, Trisomies, mosaicism
Mesenchymal cells develop into
genital or gonadal ridges
Leydig cells produce _ and are stimulated by _
testosterone, luteinizing hormone
Steroli cells produce _ and are stimulated by _
anti mullerian hormone, follicle stimulating hormone
Mesonephric ducts give rise to
seminal vesicles, vas deferens, ejaculatory duct, prostate
Mullerian ducts give rise to
Fallopian tubes
Uterus
Vagina
Primordia are indistinguishable up until week _
12
Most common 46, XX DSD
Congenital Adrenal Hyperplasia
Cause of congenital adrenal hyperplasia
Gene: CYP21A2; enzyme 21-hydroxylase
Other genes: HSD3B2, CYP11B1, CYP17A1, POR, STAR
Phenotype of 46, XX Congenital adrenal hyperplasia
virilized external genitals
US will show uterus and ovaries
XY, DSD; X-linked adrenal hypoplasia congenita
Adrenal insufficiency
Mutations in NR0B1 (affect DAX1 protein)
Hypogonadotropic hypogonadism
Undescended testes
Hypospadias
46, XY DSD - Androgen insensitivity (aka “Testicular Feminization”) syndrome
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
Kallman syndrome prevalence
1 in 10,000
Kallman syndrome genes (X-linked)
KAL1 gene ( also called ANOS1 gene)
Kallman syndrome phenotype
Hypogonadotropic hypogonadism
DECREASED SENSE OF SMELL
Can have undescended testes and or hypospadias
Can be associated with other anomalies: CL/CP, Renal agenesis, deafness
Campomelic dysplasia GENE
SOX9
Campomelic dysplasia phenotype
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
Smith Lemli Optiz syndrome gene
DHCR7
Smith Lemli Optiz phenotype
Microcephaly
Developmental delay
Cleft palate
Cardiac defects
Fused second and third toes, extra fingers and toes
Underdeveloped external genitals in males
WT1- related disorders
Frasier, Denys Drash
Frasier syndrome
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
Denys Dash
XX or XY
Abnormal development of external genitalia in males
90% develop Wilms tumor
46, XX male (SRY translocation, duplication of SOX9 or SOX3)
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
46, XY DSD- Persistent Mullerian Duct Syndrome
Mutations in MIS or the MIS receptor (AMH)
The paramesonephric ducts PERSIST; ie. there is a small uterus and paired fallopian tubes
