Differences of Sexual Development Flashcards
What teratogens affect the genitourinary tract?
Rubella, Progestational agents, Oral contraceptives, ACE inhibitors, Ethanol, Anticonvulsants, Cocaine, Vitamin A
If SRY is present, what does the bipotential gonad develop into?
Testis
What do the Leydig cells produce?
Testosterone
What to the Sertoli cells produce?
Sertoli cells produce Anti Mullerian Hormone (AMH) also known as (Mullerian inhibiting substance)
Causes regression of Mullerian duct
What hormone stimulates the production of spermatozoa in the Sertoli cells?
Follicle stimulating hormone (FSH)
What are the componenets of the Mesonephric Ducts..Wolffian system?
Seminal vesicles
Vas deferens
Ejaculatory duct
Prostate
What are the components of the Mullerian Ducts?
Fallopian tubes
Uterus
Vagina
At what week do the external genitalia become distinguisable?
Week 12
What is the Prader classification?
Anatomical classification of female genitalia. Stage 5 appears to have a penis.
What is the Quigley scale?
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
What is the chromosomal makeup of someone with Congenital Adrenal Hyperplasia?
46,XX DSD
What gonads would you see on an US of an individual with Congenital Adrenal Hyperplasia?
Uterus and ovaries
What are the genes that cause Congenital Adrenal Hyperplasia and what is the biological process?
Excess androgens from missing enzyme
21-hydroxylase – CYP21A2 gene
HSD3B2, CYP11B1, CYP17A1, POR, STAR
What is the chromosomal makeup of someone with X-linked hypoplasia congenita?
46,XY DSD
What is the gene that causes X-linked hypoplasia congenita and what is the biological process?
Adrenal insufficiency
Mutations of the NR0B1 gene
Effects DAX1 protein
What are the physical findings in X-linked hypoplasia congenita?
Hypogonadotropic hypogonadism
Undescended testes
Hypospadias
What are the genes that cause Androgen Insensitivity (aka “Testicular Feminization”) Syndrome and what is the biological process?
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
What are the physical findings in Androgen Insensitivity (aka “Testicular Feminization”) Syndrome
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
What are the genes that cause Kallmann syndrome (anosmic hypogonadism)?
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
What are the physical findings in Kallmann syndrome (anosmic hypogonadism)?
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)
What is the gene that causes Campomelic dysplasia?
SOX9 gene – autosomal dominant
What are the physical findings in Campomelic dysplasia?
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)
What is the gene and enzyme deficient in Smith Lemli Opitz?
Deficiency in the enzyme 7-dehydrocholesterol reductase
Results in an abnormality in cholesterol metabolism
Abnormal DHCR7 gene – autosomal recessive
What are the physical findings in Smith Lemli Opitz?
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
What is the gene responsible for Frasier syndrome and what is the karyotype?
Nucleotides4-5 of theintron9 in theWT1gene(11p13)
46, XY complete gonadal dysgenesis
What are the physical features of Frasier syndrome?
Progressive renal failure and 46, XY complete gonadal dysgenesis
What is the gene involved in Denys Drash and what is the physical finding?
WT1 gene
Abnormal development of external genitalia in males
What tumor develops in 90% of individuals with Denys Drash?
Wilm’s tumor
What are the physical feature of an individual with 46, XX male (SRY translocation, duplications 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 müllerian structures
Most identify as gender male; would require testosterone supplementation
What is the gene involved in Persistent Müllerian Duct syndrome and what is the karyotype?
46,XY DSD
Mutations in MISor theMIS receptor (AMH)
theparamesonephric ducts PERSIST; i.e. there is a small uterus and paired fallopian tubes
What is the gene involved in 5α-reductase deficiency and what is the karyotype?
46,XY DSD
Mutations in 5α-reductasenecessary for the conversion oftestosteroneto the more potent androgen,dihydrotestosterone (DHT)
External genitalia are partially virilized
Mesonephric ducts are intactsince they only requiretestosterone(which is still present)
Normal production of MIS from Sertoli cells causesParamesonephric duct regression
What are the physical findings in Mixed Gonadal Dysgenesis – chromosomal mosaicism?
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
What disorder accounts for 15% of patients who present with primary amenorrhea?
Mayer – Rokitansky – Kuster – Hauser Syndrome (MRKH)
What is the phenotype of Mayer – Rokitansky – Kuster – Hauser Syndrome (MRKH)?
Variable anatomy, most have a “vaginal dimple”
Can have rudimentary uterine remnants
Normal ovaries and fallopian tubes usually present
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