Sex Development 5 Flashcards
Describe the chromosomal makeup, external and internal genitalia, and abnormalities of the genitalia in the following disorders: Kleinfelter syndrome, Turner syndrome, mixed gonadal dysgenesis, 46, XY disorders of gonadal dysgenesis, 5-alpha reductase deficiency, and 21-hydroxylase deficiency.
What are the major classifications in disorders of sex development (DSD)?
- Sex chromosome DSD
- 46, XY DSD
- 46, XX DSD
What are the major diseases of sex chromosome DSD?
- Kleinfelter Syndrome (47, XXY)
- Turner Syndrome (45, XO)
- Mixed Gonadal Dysgenesis (46, XY/45,XO)
Describe the chromosomal makeup, external and internal genitalia, and abnormalities of the genitalia in Kleinfelter syndrome.
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Chromosomal makeup
- 47 XXY
-
Internal/External genitalia
- male - testis
- infancy - may be undescended
- puberty - starts to increase in size and then fail to continue to grow at small size due to fibrosis
- gynecomastia - increase in breast tumors
- tall stature with longer lower legs
- male - testis
-
Abnormalities of genitalia
- infertility, azoospermia
- insulin resistance
- language difficulties and behavioral problems
Describe the chromosomal makeup, external and internal genitalia, and abnormalities of the genitalia in Turner syndrome.
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Chromosomal makeup
- 50-60%, X monosomy
- 30% 45, X with mosaicism
- 5% 46, C with Y chromosome material with structural abnormalities
-
Internal/External genitalia
- female
-
Abnormalities of the genitalia
- ovarian dysgenesis (streak gonads)
- 10-30% have spontaneous pubertal development
- 5-16% with spontaneous menses
- 2-8% with spontaneous fertility
- infertility treatment modalities available, but have significantly increased morbidity and mortality
- ovarian dysgenesis (streak gonads)
What are some common physical findings of Turner Syndrome?
- short stature
- low hairline
- shield-shaped thorax
- widely spaced nipples
- shortened metacarpal
- small finger nails
- brown spots (nevi)
- constriction of aorta
- elbow defomity
What are some common physiological findings of Turner Syndrome?
- Lymphedema
-
Cardiac malformations
- coarctation of the aorta
- bicuspid valve
-
Renal abnormalities
- horseshoe kidney
- duplication of renal pelvis
-
Short stature
- absent SHOX gene
-
Learning disabilities
- math
- spatial
Describe the chromosomal makeup, external and internal genitalia, and abnormalities of the genitalia in mixed gonadal dysgenesis.
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Chromosomal makeup
- 45 XO
- 46 XY
-
Internal/External genitalia
- variable
- leads to highly variable PE findings
-
Abnormalities in the genitalia
- usually dysgenetic
- increased risk of tumor formation
What are some common 46 XY DSD?**
- Disorders of Gonadal Development
- complete or partial gonadal dysgenesis
- often due to transcription factor abnormalities
- Ovotesticular DSD
- ovotestis
- ovary on one side and testis on another
- ambiguous genitalia
- complete or partial gonadal dysgenesis
- Disorders of Androgen Synthesis or Action
- LH receptor mutations
- forms of congenital adrenal hyperplasia
- complete or partial androgen insensitivity
- 5-alpha reductase deficiency
What are the main features of complete androgen insensitivity syndrome?**
- 46, XY
- Mutation in androgen receptor (AR) gene
-
Characteristics
- testes
- female external genitalia
- absence of mullerian duct derivatives
- sparse sexual hair
- spontaneous pubertal breast development
- aromatization of androgens to estrogens
-
Presentation
- inguinal/labial masses
- amenorrhea
- Raised female
What are the main features of partial androgen insensitivity syndrome?**
- 46, XY
- Mutation in androgen receptor, but still partially responsive to androgen
-
Presentation
- infancy with ambiguous genitalia
-
Characteristics
- testes
- absent mullerian structures
- wolffian ducts abnormal
- undervirilized external genitalia
-
Puberty
- enlargement of phallus
- usually still small
- Raise as male or female (?)
Describe the chromosomal makeup, external and internal genitalia, and abnormalities of the genitalia in 5-alpha reductase deficiency.
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Chromosomal makeup
- 46, XY
-
Internal/External genitalia
- impaired conversion of testosterone to DHT
- undervirilization
- testes
- differentiation of wolffians tructures
- absence of mullerian derived structures
- small phallus
- urogenital sinus with perineal hypospadias
- blind vasinal pouch raise
- Abnormalities of genitalia
- at puberty, progressive virilization
- muscular development
- voice change
- phallic enlargement
- scanty facial hair
- small prostate
- low fertility
- at puberty, progressive virilization
What are the major 46, XX DSD?
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Disorders of gonadal development
-
testicular DSD
- translocation of SRY onto X chromosome
- gonads - normal testicles
- male internal and external genitalia
- ovotesticular DSD
- Transcription factor abnormalities
-
testicular DSD
-
Disorders of androgen synthesis
- maternal virilizing tumors
-
congenital adrenal hyperplasia (CAH)
- 21 hydroxylase deficiency
- 11 hydroxylase deficiency
- Placental aromatase deficiency
Describe the chromosomal makeup, external and internal genitalia, and abnormalities of the genitalia in 21 hydroxylase deficiency.
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Chromosomal makeup
- homozygous or compound heterozygous mutations
- 46, XX
- 46, XY
-
types
- classical salt wasting (more common)
- simple virilizing
-
Internal/External genitalia
- ovaries
- female internally
- variable ambiguity externally
-
Abnormalities of the genitalia
-
classic form
- presents in infancy
- ambiguous genitalia and salt-wasting
- replace cortisol and aldosterone
-
non-classic form
- presents later in life
- mild virilization
-
classic form