Disorders of sexual differentiation Flashcards
disorders of sexual differentiation (DSD)
- gonadal dysgenesis - gonads not forming properly , missing parts of x or Y chromosome
- sexual reversal - xx showing male phenotype or XY showing female phenotype
- intersex - ambiguous, have features of both
DSD: gonadal dysgenesis
sexual differentiation is incomplete, usually missing SRY in male, or partial or complete deletion of second X in female. Also used as general description of abnormal development of the gonads.
Turner syndrome
DSD: sex reversal
phenotype does not match genotype, ie may be a genotypical male but external genitalia looks female
DSD: intersex
have some components of both tracts or have ambigious genitalia, sex of infant difficult to determine
What is androgen insensitivity syndrome (AIS)
genotypical male but appears female (due to insensitivity to testosterone, made but no effect of testosterone)
-1 :20,000
-external genitalia appears female
- no uterus or fallopian tube - characterised by primary amenorrhea (so when you go to check it out you find out your a male)
-ultrasound and karyotype with male levels of androgens
-hormonal puberty also feminised due to androgen -> eostrogen by aromatase.
-differentiation of gender role and identity usually feminine, in adulthood conforms to typical heterosexual female expectations.
What happens if XY individual makes testosterone but has no effect (AIS)?
-testes form and make AMH so mullerian ducts regress
-no differentiation of wolffian ducts due to insensitivity of testosterone
-no external male genitalia
What is partial AIS?
-spectrum of phenotypes including almost normal female external genitalia through ambigious genitalia (perineoscrotal hypospadia, microphallus, cryptorchidism)
-at puberty male characteristics may not be very pronounced.
-many develop identity that matches theor assigned gender, around 20% desire to change gender.
What happens if XY male is unable to make or respond to AMH in utero ( persistent Mullerian duct syndrome)?
-testes form and either fail to make AMH or AMH receptor absent
-mullerian duct remains
-differentiation of wolffian ducts and masculinised external genitalia
What is PMDS?
-PMDS type 1 results from mutations of gene for AMH on chromosome 19
- PMDS type 2 results from mutations of the gene for the AMH receptor on Chr 12
-both autosomal recessive conditions with expression usually limited to XY offspring.
What are common presentation of PMDS?
-60-70% of cases have intra-abdomial mullerian structures and testes in a position of 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)
-all have increased risk of malignant transformation
Treatments of PMDS
-surgery (orchiopexy) to retrieve the testes and position in the scrotum, testosterone replacement at puberty is an option.
-removal of uterus dissection of Mullerian tissue away from the vas deferens/ epididymis
-Laparoscopic hysterectomy may prevent occurrences of neoplastic tissue formation
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Why, testosterone is made but not DHT?
- 5 alpha reductase deficiency
What happens when there is 5 alpha reductase deficiency?
-bc this enzyme converts testosterone to dihydrotestosterone
-AMH still forms and mullerian ducts regress
-testosterone forms and growth of wolffian duct
-no external genitalia of males
Turner syndrome
-XO have failure of ovarian function, need two X for it
- streak ovaries = ovarian dysgenesis
-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
What happens if XX female is exposed to high levels of androgens in utero(CAH)?
- No SRY so no testes and no AMH
-Mullerian duct remains - Masculinised external genitalia but androgen levels not usually high enough to rescue wolffian duct.
