Disorders of Sex Development Flashcards
What structures do the Wolffian ducts and Mullerian ducts become?
- Wolffian: epididymis, vas deferens, seminal vesicles
- Mullerian: fallopian tubes, uterus, upper vagina
What do the following ectodermal structures become?
- Genital tubercle
- Urethral folds
- Labioscrotal folds
- Genital tubercle: clitoris/penis
- Urethral folds: labia minora/penile urethra
- Labioscrotal folds: labia majora/scrotum
Name 5 genes important for Wolffian duct formation
- SRY (sex-determining region on Y chromosome)
- SF1 (steroidogenic factor 1)
- SOX9 (SRY-related HMG box factor)
- FGF9 (represses WNT4 expression)
- GATA4
- DHH
- AMH
- WT1
- PKD1
- PTEN
- DICER
What enzyme is important for development of male external genitalia
5 alpha reductase (converts testosterone to DHT)
There are 6-7 million ovarian follicles present at 25 weeks gestation. How many persist at term?
2 million
Note: The presence of germ cell sis critical for stabilization of the over. Without them, ovaries become fibrous and do not synthesize ovarian hormones.
Name 3 genes important for ovary development
- WNT4
- RSPO1 (R-spondin 1)
- CTNNB1 (beta-catenin)
- FST (follistatin)
- FOXL2
- NROB1 (DAX1)
Define “disorder of sex development”
- Congenital conditions in which development of chromosomal, gonadal and genital sex is atypical
- Broad category to replace the term intersex
- Classifications:
- 46,XX (virilized female)
- 46,XY (undervirilized male)
- Sex chromosome DSD (mosaicism, Turner, Klinefelter)
List the differential diagnosis for undervirilized male
- Abnormal response to androgens
- Androgen insensitivity (complete/partial)
- Endocrine disruptors (phenobarbital, phenytoin)
- Abormal androgen synthesis
- 5 alpha reductase deficiency
- 17 beta hydroxysteroid dehydrogenase deficiency (block between androstenedione and testo)
- LH receptor defect
- CAH
- 3 beta hydroxysteroid dehydraogenase deficiency
- 17 alpha hydroxylase deficiency
- StAR protein deficiency
- P450 side chain cleavage deficiency (CYP11A1)
- Diminished testicular activity
- Gonadal dysgenesis
- Persistent mullerian duct syndrome
- Vanishing testes (late in development)
- Testicular regression syndrome (early in development)
- DAX1 duplication
- Genetic mutations
- SRY deletion/mutation
- DAX1 duplication
- SOX 9 deletion/mutation
- SF1 deletion/mutation
- WT1 deletion/mutation
- Syndromes
- Smith-Lemli-Opitz
- Robinow
- VATER
- CHARGE
- Bladder extrophy
- IMAGe (CDKN1c)
Describe the 5 Prader stages
- Clitoromegaly without labial fusion
- Clitoromegaly with posterior labial fusion
- Greater degree of clitoromegaly, single perineal urogenital orifice, almost complete labial fusion
- Increasingly phallic clitoris, urethra-like urogenital sinus at base of clitoris, complete labial fusion
- Penile clitoris, urethral meatus at tip of phallus, scrotum-like labia
List 4 things to consider when deciding on sex of rearing in ambiguous genitalia
- Diagnosis (including karyotype). What is known about gender identity in this specific condition
- Degree of virilization as a marker of brain androgenization
- Genitalia (internal and external). Appearance, corrective surgical possibilities, sexual function, fertility
- Socio-cultural background and expectations
What should you desribe on the physical exam for ambiguous genitalia?
- Labioscrotal folds: fused? rugated? hyperpigmented?
- Genital tubercle: length and diameter
- Presence or absence of palpable gonads
- Number of perineal openings
- Location of urethral opening (may need to visualize urinary stream)
- Anogenital ratio (anus to posterior fourchette/anus to base of phallus, ratio >0.5 suggests virilization)
- Symmetry or asymmetry of external genitalia
- Any other findings: dysmorphic features, etc
