Columbus: disorders of sexual differentiation Flashcards
Where is the SRY gene located?
Short arm of the Y chromosome
What is the “default” sexual differentiation?
The absence of what hormone leads to uterine development?
The absence of what gene leads to ovarian development?
Female
Mullerian inhibitory factor or anti-mullerian hormone
SRY gene
What is the most common cause of ambiguous genitalia?
Congenital adrenal hyperplasia
What is the most common cause of CAH?
How is this diagnosed?
21-hydroxylase deficiency
17 OH-progesterone above 5 ng/mL
What is the chromosome compliment in congenital adrenal hyperplasia?
What causes CAH?
46 XX
Maternal ingestion of androgenic steroids
Androgen-producing tumor in the mother or fetus
What is the incidence of CAH?
What ethnic backgrounds have increased risk?
1 in 15,000
European/Ashkenazi Jewish, Hispanic, Slavic, Italian
In addition to ambiguous genitalia, what is the other significant feature of classic CAH?
When does it present?
Severe salt wasting
Hyponatremia, hyperkalemia, hypertension, cardiovascular collapse
One week; often unrecognized in males due to normal appearing genitalia
Describe nonclassic CAH.
Not associated with ambiguous genitalia; presents later in life and often confused with PCOS
How can known female carriers of CAH be evaluated and managed during pregnancy?
Genetic diagnosis can be offered via CVS or amniocentesis
Dexamethasone can be started at the time pregnancy is diagnosed to prevent female genital virilization; this needs to be given 6-7 weeks after conception
What is the effect of testosterone on sexual differentiation?
Causes differentiation of wolffian structures including seminal vesicles, ejaculatory ducts, epididymis, vas deferens.
Causes testes to descend.
Causes external genitals to form in response to testosterone to dihydrotestosterone
What is the differential diagnosis for 46XY disorder of sexual development?
5 alpha reductase deficiency
Androgen insensitivity, partial or complete
Gonadal dysgenesis
Multiple rare autosomal recessive androgen synthesis disorders
What is 5 alpha reductase deficiency?
What is the inheritance pattern?
Mullerian features present? Wolffian structures present? External genitalia phenotype? Breasts? Sperm?
Wide range of external genitalia from female to male with testes in inguinal canal. Also called penne al dolce due to virilization at puberty as testicular testosterone increases.
Autosomal recessive
Absent Male Female to male or ambiguous No Decreased
What is androgen insensitivity?
What is the inheritance pattern?
What is the general phenotype? Mullerian structures present? Wolffian structures? External genitalia phenotype? Breasts? Sperm?
Mutation of androgen receptor gene with impaired binding of testosterone and DHT: normal androgen levels with 46XY karyotype
X-linked
Partial insensitivity leads to ambiguous genitalia; complete leads to testicular feminization with female external genitalia; tend to be tall, thin hairless bodies that present with amenorrhea
Absent Absent Female; ambiguous if partial Yes; maybe if partial No
What is the patient’s primary concern with androgen insensitivity?
What is the patient’s major health risk that needs to be considered?
Short blind-pouch vagina may require vaginal dilation therapy
Abdominal or intraperitoneal gonads are at increased risk of cancer and should be removed after puberty
What is gonadal dysgenesis?
What is the phenotype?
Chromosomes? Gonads? Mullerian duct? Wolffian duct? External genitalia?
Includes Turner’s syndrome and Swyer syndrome
Female phenotype
Turner's is 45X; Swyer is 46XY Streak gonads Present Absent Female
