Differences of Sexual Development

Question 1

What teratogens affect the genitourinary tract?

Answer 1

Rubella, Progestational agents, Oral contraceptives, ACE inhibitors, Ethanol, Anticonvulsants, Cocaine, Vitamin A

Question 2

If SRY is present, what does the bipotential gonad develop into?

Answer 2

Testis

Question 3

What do the Leydig cells produce?

Answer 3

Testosterone

Question 4

What to the Sertoli cells produce?

Answer 4

Sertoli cells produce Anti Mullerian Hormone (AMH) also known as (Mullerian inhibiting substance)

Causes regression of Mullerian duct

Question 5

What hormone stimulates the production of spermatozoa in the Sertoli cells?

Answer 5

Follicle stimulating hormone (FSH)

Question 6

What are the componenets of the Mesonephric Ducts..Wolffian system?

Answer 6

Seminal vesicles
Vas deferens
Ejaculatory duct
Prostate

Question 7

What are the components of the Mullerian Ducts?

Answer 7

Fallopian tubes
Uterus
Vagina

Question 8

At what week do the external genitalia become distinguisable?

Answer 8

Week 12

Question 9

What is the Prader classification?

Answer 9

Anatomical classification of female genitalia. Stage 5 appears to have a penis.

Question 10

What is the Quigley scale?

Answer 10

The Quigley scale is a descriptive, visual system of phenotypic grading that defines seven classes between “fully masculinized” and “fully feminized” genitalia.

1 has penis

Question 11

What is the chromosomal makeup of someone with Congenital Adrenal Hyperplasia?

Answer 11

46,XX DSD

Question 12

What gonads would you see on an US of an individual with Congenital Adrenal Hyperplasia?

Answer 12

Uterus and ovaries

Question 13

What are the genes that cause Congenital Adrenal Hyperplasia and what is the biological process?

Answer 13

Excess androgens from missing enzyme

21-hydroxylase – CYP21A2 gene
HSD3B2, CYP11B1, CYP17A1, POR, STAR

Question 14

What is the chromosomal makeup of someone with X-linked hypoplasia congenita?

Answer 14

46,XY DSD

Question 15

What is the gene that causes X-linked hypoplasia congenita and what is the biological process?

Answer 15

Adrenal insufficiency

Mutations of the NR0B1 gene
Effects DAX1 protein

Question 16

What are the physical findings in X-linked hypoplasia congenita?

Answer 16

Hypogonadotropic hypogonadism
Undescended testes
Hypospadias

Question 17

What are the genes that cause Androgen Insensitivity (aka “Testicular Feminization”) Syndrome and what is the biological process?

Answer 17

X-linked

Complete or Partial (CAIS or PAIS)

Mutations in the androgen receptor gene (not to be confused with autosomal recessive)

Lack of virilization of due to inability of AR to bind testosterone or DHT

Question 18

What are the physical findings in Androgen Insensitivity (aka “Testicular Feminization”) Syndrome

Answer 18

Relatively normal female external genitaliabutundescended testes
Mesonephric ducts are rudimentary or lackingdue to insensitivity to testosterone signaling
Normal production of MIS from Sertoli cells causesMüllerian duct regression, so no oviducts, uterus or cervix

Question 19

What are the genes that cause Kallmann syndrome (anosmic hypogonadism)?

Answer 19

X-linked recessive, autosomal dominant or autosomal recessive depending on what gene is responsible

KAL1 gene (also called the ANOS1 gene) causing Kallmann syndrome 1 is inherited in an X-linked recessive manner
FGFR1, PROKR2, PROK2, CHD7 or FGF8 genes (causing KS types 2, 3, 4, 5 and 6, respectively) autosomal dominant
PROKR2 and PROK2 can also be inherited in an autosomal recessive manner

Question 20

What are the physical findings in Kallmann syndrome (anosmic hypogonadism)?

Answer 20

Hypogonadotropic Hypogonadism
Decreased sense of smell
Can have undescended testes and/or hypospadias
Can be associated with other anomalies (cleft lip/palate, renal agenesis, deafness)

Question 21

What is the gene that causes Campomelic dysplasia?

Answer 21

SOX9 gene – autosomal dominant

Question 22

What are the physical findings in Campomelic dysplasia?

Answer 22

Large head (macrocephaly)
Short, bowed limbs
Dislocated hips
11 pairs of ribs instead of 12
Small chest and lungs
Club feet
Distinctive facial features, including small chin, prominent eyes, and a flat face
Cleft palatewith a small lower jaw
External genitalia that do not look male or female or normal female genitalia with a typical malechromosomepattern (46,XY)

Question 23

What is the gene and enzyme deficient in Smith Lemli Opitz?

Answer 23

Deficiency in the enzyme 7-dehydrocholesterol reductase

Results in an abnormality in cholesterol metabolism

Abnormal DHCR7 gene – autosomal recessive

Question 24

What are the physical findings in Smith Lemli Opitz?

Answer 24

Small head (microcephaly)
Developmental delay
Particular facial features, cleft palate
Cardiac defects
Fused second and third toes, extra fingers and toes and
Underdeveloped external genitals in males

Question 25

What is the gene responsible for Frasier syndrome and what is the karyotype?

Answer 25

Nucleotides 4-5 of the intron 9 in the WT1 gene (11p13) 46, XY complete gonadal dysgenesis

Question 26

What are the physical features of Frasier syndrome?

Answer 26

Progressive renal failure and 46, XY complete gonadal dysgenesis

Question 27

What is the gene involved in Denys Drash and what is the physical finding?

Answer 27

WT1 gene Abnormal development of external genitalia in males

Question 28

What tumor develops in 90% of individuals with Denys Drash?

Answer 28

Wilm's tumor

Question 29

What are the physical feature of an individual with 46, XX male (SRY translocation, duplications of SOX9 or SOX3)?

Answer 29

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

Question 30

What is the gene involved in Persistent Müllerian Duct syndrome and what is the karyotype?

Answer 30

46,XY DSD Mutations in MIS or the MIS receptor (AMH) the paramesonephric ducts PERSIST; i.e. there is a small uterus and paired fallopian tubes

Question 31

What is the gene involved in 5α-reductase deficiency and what is the karyotype?

Answer 31

46,XY DSD Mutations in 5α-reductase necessary for the conversion of testosterone to the more potent androgen, dihydrotestosterone (DHT) External genitalia are partially virilized Mesonephric ducts are intact since they only require testosterone (which is still present) Normal production of MIS from Sertoli cells causes Paramesonephric duct regression

Question 32

What are the physical findings in Mixed Gonadal Dysgenesis – chromosomal mosaicism?

Answer 32

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

Question 33

What disorder accounts for 15% of patients who present with primary amenorrhea?

Answer 33

Mayer – Rokitansky – Kuster – Hauser Syndrome (MRKH)

Question 34

What is the phenotype of Mayer – Rokitansky – Kuster – Hauser Syndrome (MRKH)?

Answer 34

Variable anatomy, most have a “vaginal dimple” Can have rudimentary uterine remnants Normal ovaries and fallopian tubes usually present Another checklist or decision aid