Disorders of sexual differentiation Flashcards
What is Gonadal dysgenesis
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.
What is Sex reversal
Phenotype does not match genotype,
ie may be male genotypically but externally look like a female.
What is Intersex
Have some components of both tracts or have ambiguous genitalia.
Sex of infant difficult to determine.
Androgen insensitivity syndrome (AIS) - simple terms
Testosterone is made but has no effect.
Androgen insensitivity syndrome (AIS) features
Testes? AMH? Mullerian duct? Wolffian duct? External genitalia (male or female?)?
Testes form and make AMH so Mullerian ducts regress.
No differentiation of Wolffian ducts
No external male genitalia
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)
- 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.
Partial AIS characterisation?
Spectrum of phenotypes or ambiguous including almost normal female external genitalia through ambiguous genitalia
Minor genital deviations go unnoticed or may be surgically repaired
Persistent Mullerian duct syndrome
simply…
When XY male is unable to make or respond to AMH in utero.
PMDS type I results from mutations of the gene for ____ on chromosome ____?
AMH on chromosome 19
PMDS type II results from mutations of the gene for ____ on chromosome ____?
AMH receptor (AMH-RII) on chromosome 12
Both PMDS types are…
autosomal recessive conditions
Persistent Mullerian duct syndrome Features:
Testes? AMH? Mullerian duct? Wolffian duct? External genitalia (male or female?)?
Testes form and either fail to make AMH or AMH receptor absent.
Mullerian ducts remain.
Differentiation of Wolffian ducts
Masculinised external genitalia
Persistent Mullerian duct syndrome Common presentation
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.
Persistent Mullerian duct syndrome Treatments…
Surgery?
Removal of?
Laparoscopic hysterectomy may prevent the occurrences of ?
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.
5-α-reductase deficiency simply
When is an XY individual, Testosterone is made but not DHT
5-α-reductase deficiency
Testes? AMH? Mullerian duct? Wolffian duct? External genitalia (male or female?)?
Testes form and make AMH so Mullerian ducts regress.
Wolffian ducts develop.
No external male genitalia.
5-α-reductase deficiency common presentation
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.
Turners syndrome: 1:3000 simply
45 XO
No Y nor second X chromosome
XO have failure of ovarian function. ‘Streak’ ovaries = ovarian dysgenesis
Turners syndrome presentation
What is present?
Are they fertile?
What could they have?
What sort of support is given
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.
Congenital adrenal hyperplasia simply
1:15,000
When XX female is exposed to high levels of androgens in utero
CAH presentation
Completeness of the enzyme block varies. May have developed Wolffian structures and ambiguous masculinised external genitalia or hirsutism .
What do those with Congenital adrenal hyperplasia (CAH) need to be aware of?
Need to be aware of possibility of ‘salt-wasting’ due to lack of aldosterone, this can be lethal.
CAH treatment
Treatment with glucocorticoids to correct feedback.
