Columbus: disorders of sexual differentiation Flashcards

0
Q

Where is the SRY gene located?

A

Short arm of the Y chromosome

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1
Q

What is the “default” sexual differentiation?

The absence of what hormone leads to uterine development?

The absence of what gene leads to ovarian development?

A

Female

Mullerian inhibitory factor or anti-mullerian hormone

SRY gene

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2
Q

What is the most common cause of ambiguous genitalia?

A

Congenital adrenal hyperplasia

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3
Q

What is the most common cause of CAH?

How is this diagnosed?

A

21-hydroxylase deficiency

17 OH-progesterone above 5 ng/mL

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4
Q

What is the chromosome compliment in congenital adrenal hyperplasia?

What causes CAH?

A

46 XX

Maternal ingestion of androgenic steroids
Androgen-producing tumor in the mother or fetus

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5
Q

What is the incidence of CAH?

What ethnic backgrounds have increased risk?

A

1 in 15,000

European/Ashkenazi Jewish, Hispanic, Slavic, Italian

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6
Q

In addition to ambiguous genitalia, what is the other significant feature of classic CAH?

When does it present?

A

Severe salt wasting
Hyponatremia, hyperkalemia, hypertension, cardiovascular collapse

One week; often unrecognized in males due to normal appearing genitalia

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7
Q

Describe nonclassic CAH.

A

Not associated with ambiguous genitalia; presents later in life and often confused with PCOS

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8
Q

How can known female carriers of CAH be evaluated and managed during pregnancy?

A

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

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9
Q

What is the effect of testosterone on sexual differentiation?

A

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

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10
Q

What is the differential diagnosis for 46XY disorder of sexual development?

A

5 alpha reductase deficiency
Androgen insensitivity, partial or complete
Gonadal dysgenesis
Multiple rare autosomal recessive androgen synthesis disorders

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11
Q

What is 5 alpha reductase deficiency?

What is the inheritance pattern?

Mullerian features present?
Wolffian structures present?
External genitalia phenotype?
Breasts?
Sperm?
A

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
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12
Q

What is androgen insensitivity?

What is the inheritance pattern?

What is the general phenotype? Mullerian structures present?
Wolffian structures?
External genitalia phenotype?
Breasts?
Sperm?
A

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
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13
Q

What is the patient’s primary concern with androgen insensitivity?

What is the patient’s major health risk that needs to be considered?

A

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

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14
Q

What is gonadal dysgenesis?

What is the phenotype?

Chromosomes?
Gonads?
Mullerian duct?
Wolffian duct?
External genitalia?
A

Includes Turner’s syndrome and Swyer syndrome

Female phenotype

Turner's is 45X; Swyer is 46XY
Streak gonads
Present
Absent
Female
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15
Q

What is ovatesticular DSD?

A

Both ovarian and testicular tissue: most are 46XX but can also be chimeric or mosaic; true hermaphrodite
The amount of functional testicular tissue determines the phenotype; most will have uterus and ambiguous genitalia, 60% menstruate

16
Q

What history should be collected from parents of an infant with ambiguous genitalia?

A

Maternal history especially androgen ingestion, consanguinity, history of unexplained neonatal death

17
Q

What laboratory testing should be ordered for an infant with ambiguous genitalia?

What imaging should be considered?

A

Electrolytes are the most important
Karyotype, 17 OHP, DHEAS, testosterone, LH, FSH, dihydrotestosterone

Ultrasound and MRI

18
Q

What other congenital anomalies are associated with mullerian defects?

A

Urinary tract 20-25%
GI tract 12%
Musculoskeletal 10-12%
Heart, eye, ear 6%

19
Q

What is the other name associated with vaginal agenesis?

How is vaginal agenesis treated?

A

Mayer-Rokitansky-Küster-Hauser syndrome

Dilators or McIndow or Vecchietti vaginoplasty procedures

20
Q

What treatment is recommended for unicornuate, bicornuate, or uterine didelphys?

What percentage of patients with uterine didelphys or unicornuate uterus will have urinary tract anomalies?

What treatment is recommended for septate uterus?

A

Usually nothing unless unilateral obstructed vagina

80% chance of renal agenesis

Resection to prevent miscarriage