Disorders of sexual differentiation

Question 1

What is Gonadal dysgenesis

Answer 1

Sexual differentiation is incomplete.

Usually missing SRY in male, or partial or complete deletion of second X in female.

Also used as a general description of abnormal development of the gonads.

Question 2

What is Sex reversal

Answer 2

Phenotype does not match genotype,

ie may be male genotypically but externally look like a female.

Question 3

What is Intersex

Answer 3

Have some components of both tracts or have ambiguous genitalia.

Sex of infant difficult to determine.

Question 4

Androgen insensitivity syndrome (AIS) - simple terms

Answer 4

Testosterone is made but has no effect.

Question 5

Androgen insensitivity syndrome (AIS) features

Testes? AMH? Mullerian duct? Wolffian duct? External genitalia (male or female?)?

Answer 5

Testes form and make AMH so Mullerian ducts regress.

No differentiation of Wolffian ducts

No external male genitalia

Question 6

Complete AIS characterisation?

• Undescended ________
• No _________ (structures)?
• External genitalia appear __________ (male/female)?
• Usually present with ___________. Lack of body hair is a clue.
• Ultrasound scan and karyotype with __________ of androgens.
• Sex assignment and rearing almost always _______ (male/female)

Answer 6

• Undescended testes.
• No uterus or fallopian tubes
• External genitalia appear female - abbreviated blind vaginal pouch.
• Usually present with primary amenorrhoea. Lack of body hair is a clue.
• Ultrasound scan and karyotype with male levels of androgens.
• Sex assignment and rearing almost always female.

Question 7

Partial AIS characterisation?

Answer 7

Spectrum of phenotypes or ambiguous including almost normal female external genitalia through ambiguous genitalia

Minor genital deviations go unnoticed or may be surgically repaired

Question 8

Persistent Mullerian duct syndrome
simply…

Answer 8

When XY male is unable to make or respond to AMH in utero.

Question 9

PMDS type I results from mutations of the gene for ____ on chromosome ____?

Answer 9

AMH on chromosome 19

Question 10

PMDS type II results from mutations of the gene for ____ on chromosome ____?

Answer 10

AMH receptor (AMH-RII) on chromosome 12

Question 11

Both PMDS types are…

Answer 11

autosomal recessive conditions

Question 12

Persistent Mullerian duct syndrome Features:

Testes? AMH? Mullerian duct? Wolffian duct? External genitalia (male or female?)?

Answer 12

Testes form and either fail to make AMH or AMH receptor absent.

Mullerian ducts remain.

Differentiation of Wolffian ducts

Masculinised external genitalia

Question 13

Persistent Mullerian duct syndrome Common presentation

Answer 13

60–70% of cases have intra-abdominal Mullerian structures and testes in a position simulating that of the ovaries

20–30% have one testis in a hernial sac or scrotum together with Mullerian structures.

10% have both testes located in the same hernial sac (transverse testicular ectopia) along with the uterine tubes and/or uterine structures.

All have increased risk of malignant transformation.

Question 14

Persistent Mullerian duct syndrome Treatments…

Surgery?
Removal of?
Laparoscopic hysterectomy may prevent the occurrences of ?

Answer 14

Surgery (orchiopexy) to retrieve the testes and position them in the scrotum;
If testes cannot be retrieved, testosterone replacement at puberty is an option.

Removal of uterus dissection of Müllerian tissue away from the vas deferens/epididymis.

Laparoscopic hysterectomy may prevent the occurrences of neoplastic tissue formation.

Question 15

5-α-reductase deficiency simply

Answer 15

When is an XY individual, Testosterone is made but not DHT

Question 16

5-α-reductase deficiency

Testes? AMH? Mullerian duct? Wolffian duct? External genitalia (male or female?)?

Answer 16

Testes form and make AMH so Mullerian ducts regress.

Wolffian ducts develop.

No external male genitalia.

Question 17

5-α-reductase deficiency common presentation

Answer 17

Testes form, AMH acts, testosterone acts.

Internal structures form. External male structures do not fully develop.

May appear mainly female or may have ambiguous genitalia such as labioscrotal folds or clitoridean penis.

The degree of the enzyme block varies and so therefore does the presentation.

Need to assess potential as high testosterone level which will occur at adrenarche and puberty may induce virilisation.

Question 18

Turners syndrome: 1:3000 simply

Answer 18

45 XO

No Y nor second X chromosome

XO have failure of ovarian function. ‘Streak’ ovaries = ovarian dysgenesis

Question 19

Turners syndrome presentation

What is present?
Are they fertile?
What could they have?

What sort of support is given

Answer 19

Uterus and tubes are present, may be small or other defects in growth and development.

May be fertile, many have mosaicism. Female gender.

Hormone support of bones and uterus.

Question 20

Congenital adrenal hyperplasia simply

1:15,000

Answer 20

When XX female is exposed to high levels of androgens in utero

Question 21

CAH presentation

Answer 21

Completeness of the enzyme block varies. May have developed Wolffian structures and ambiguous masculinised external genitalia or hirsutism .

Question 22

What do those with Congenital adrenal hyperplasia (CAH) need to be aware of?

Answer 22

Need to be aware of possibility of ‘salt-wasting’ due to lack of aldosterone, this can be lethal.

Question 23

CAH treatment

Answer 23

Treatment with glucocorticoids to correct feedback.