Disorders of Sexual Differentiation Flashcards
(49 cards)
What is gonadal dysgenesis?
Incomplete sexual differentiation
- missing SRY in male
- partial / complete deletion of second X in female
General description of abnormal gonad development
What is sex reversal?
Phenotype doesn’t match genotype
May be male genotypically (XY) but externally looks female
What is intersex?
Components of both tracts / have ambiguous genitalia
Sex of infant difficult to determine. (e.g. v. large clitoris or v. small penis) - DSD
Describe androgen insensitivity syndrome (AIS)
XY individual
Testosterone produced but has no effect
What are the internal and external genitalia of an individual with AIS?
Testes form (undescended) and make AMH so Mullerian ducts regress.
No differentiation of Wolffian ducts
No external male genitalia - appear F
What is the incidence rate of complete AIS?
Complete AIS - incidence 1:20,000 (46XY)
How may an AIS individual present?
Primary amenorrhoea
Lack of body hair
U/s scan and karyotype show male levels androgens
Hormonal puberty causes feminization w/out intervention due to aromatization of endogenous androgens into estrogens = Lacking response to androgen.
What is the incidence rate of partial AIS?
Incidence unknown but on a spectrum (46XY)
Describe the spectrum of partial AIS
Spectrum of phenotypes including almost normal female external genitalia through ambiguous genitalia (perineoscrotal hypospadias, microphallus, cryptorchidism).
What is the prognosis of partial AIS?
Minor genital deviations go unnoticed or may be surgically repaired
How does partial AIS present at puberty?
Development of male secondary characteristics not very pronounced
Pubertal gynecomastia can occur (dec androgen : estrogen ratio)
Ambiguous genitalia surgically corrected or via Androgen therapy
What gender do partial AIS individuals identify with?
Majority develop identity commensurate with assigned gender
~20% desire to change gender usually in adolescence or adulthood
What is persistent mullerian duct syndrome (PMDS)?
XY male unable to produce / respond to AMH in utero
- PMDS I and PMDS II
What causes PMDS I?
PMDS type I results from mutations of AMH gene on chromosome 19
What causes PMDS II?
PMDS type II results from mutations of the AMH receptor gene (AMH-RII) on chromosome 12.
Describe the mendelian inheritance pattern of PMDS I and II
Both autosomal recessive conditions with expression usually limited to XY offspring
1 normal + 1 abnormal = carrier
Homozygous for gene required for mutation
Describe the gonadal formation for PMDS patients
Testes form and either fail to make AMH or AMH receptor absent.
Outline the external and internal genitalia of PMDS individuals
Mullerian ducts remain.
Differentiation of Wolffian ducts and masculinised external genitalia due to testosterone on genital skin
Describe the varying common presentations of PMDS patients
60–70%: intra-abdominal Mullerian structures, testes in position of ovaries
20–30%:one testis in a hernial sac / scrotum together with Mullerian structures
10%: both testes located in same hernial sac (transverse testicular ectopia) along w/ uterine tubes and/or uterine structures.
All have increased risk of malignant transformation.
What are the treatment options for PMDS?
surgery
hysterectomy
How is surgery used to treat PMDS?
Surgery (orchiopexy) to retrieve testes and position them in scrotum
If testes cannot be retrieved, testosterone replacement at puberty is an option.
How does a hysterectomy help treat PMDS?
Uterus removal, dissection of Müllerian tissue away from vas deferens/epididymis
Laparoscopic hysterectomy may prevent occurrences of neoplastic tissue formation
What is the effect of 5-α-reductase deficiency?
XY individual can produce testosterone but cannot convert to DHT
Describe the external genitalia of someone with 5-α-reductase deficiency
Testes form and make AMH so Mullerian ducts regress.
Wolffian ducts develop
No external male genitals.
