Disorders Of Sexual Differentiation Flashcards
Define gonadal dygenesis - men + women missing… (3)
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.
Define sex reversal
Phenotype does not match genotype, ie may be male genotypically but externally look like a female.
Define intersex
Have some components of both tracts or have ambiguous genitalia. Sex of infant difficult to determine.
Why disorder of sexual diff/DSD?
Patients prefer to be known as someone with a ‘disorder of sexual differentiation’ or DSD.
Terms such as ‘pseudohermaphrodite’ and, ‘testicular feminisation’ are now obsolete.
What happens if in an XY individual…testosterone is made but has no effect.
How would this happen?
-Testes form and make AMH so Mullerian ducts regress.
-No differentiation of Wolffian ducts
-No external male genitalia
Androgen insensitivity syndrome (AIS)
Explain AIS and diagnosis/signs (8)
Complete AIS - incidence 1:20,000 (46XY)
•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.
•Hormonal puberty may be feminizing without intervention due to aromatization of endogenous androgens to estrogens. Lacking response to androgen.
•Sex assignment and rearing almost always female.
•Differentiation of gender role and identity usually feminine. In adulthood, sexuality often conforms to typical heterosexual female expectations.
Explain partial AIS - male affected (4)
Partial AIS - incidence unknown - spectrum (46XY)
•Spectrum of phenotypes including almost normal female external genitalia through ambiguous genitalia (perineoscrotal hypospadias, microphallus, cryptorchidism).
•Minor genital deviations go unnoticed or may be surgically repaired.
•At puberty development of male secondary characteristics may not be very pronounced. In some cases pubertal gynecomastia (androgen/estrogen ratio) or ambiguous genitalia surgically corrected. Androgen therapy in some cases.
•Majority of individuals develop an identity commensurate with their assigned gender - around 20% desire to change gender usually in adolescence or adulthood.
What happens if XY male is unable to make or respond to AMH in utero? (4)
Persistent Mullerian duct syndrome.
-Testes form and either fail to make AMH or AMH receptor absent.
- Mullerian ducts remain.
- Differentiation of Wolffian ducts and masculinised external genitalia
Explain the genetics persistent Müllerian duct syndrome (3)
PMDS type I results from mutations of the gene for AMH on chromosome 19.
PMDS type II results from mutations of the gene for the AMH receptor (AMH-RII) on chromosome 12.
Both autosomal recessive conditions with expression usually limited to XY offspring.
Explain common presentation of Persistent Müllerian duct syndrome -%’s (4)
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.
Treatments for Persistent Müllerian duct syndrome (3)
Treatments…
•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.
What happens if in an XY individual… testosterone is made but not DHT?
-Testes form and make AMH so Mullerian ducts regress.
-Wolffian ducts develop
-No external male genitalia.
5-α-reductase deficiency
Explain 5-α-reductase deficiency (5)
5α-reductase deficiency – incidence varies enormously (46XY)
•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.
•Both testosterone and dihydrotestosterone (DHT) are capable of masculinising the brain in non-human primates so some brain masculinisation in utero possible with this condition.
What happens if…45 XO?
Turner Syndrome
Explain Turner Syndrome (4)
Turners syndrome: 1:3000
•XO have failure of ovarian function. ‘Streak’ ovaries = ovarian dysgenesis - illustrates that we need two X’s for ovarian development.
•Uterus and tubes are present, may be small or other defects in growth and development. Wide spectrum of phenotypic disorders and severity.
•May be fertile, many have mosaicism. Female gender.
•Hormone support of bones and uterus.
