Sex Development 5

Question 1

What are the major classifications in disorders of sex development (DSD)?

Answer 1

• Sex chromosome DSD
• 46, XY DSD
• 46, XX DSD

Question 2

What are the major diseases of sex chromosome DSD?

Answer 2

• Kleinfelter Syndrome (47, XXY)
• Turner Syndrome (45, XO)
• Mixed Gonadal Dysgenesis (46, XY/45,XO)

Question 3

Describe the chromosomal makeup, external and internal genitalia, and abnormalities of the genitalia in Kleinfelter syndrome.

Answer 3

• 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
• Abnormalities of genitalia
  
  • infertility, azoospermia
  • insulin resistance
  • language difficulties and behavioral problems

Question 4

Describe the chromosomal makeup, external and internal genitalia, and abnormalities of the genitalia in Turner syndrome.

Answer 4

• 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

Question 5

What are some common physical findings of Turner Syndrome?

Answer 5

• short stature
• low hairline
• shield-shaped thorax
• widely spaced nipples
• shortened metacarpal
• small finger nails
• brown spots (nevi)
• constriction of aorta
• elbow defomity

Question 6

What are some common physiological findings of Turner Syndrome?

Answer 6

• 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

Question 7

Describe the chromosomal makeup, external and internal genitalia, and abnormalities of the genitalia in mixed gonadal dysgenesis.

Answer 7

• 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

Question 8

What are some common 46 XY DSD?**

Answer 8

• 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
• Disorders of Androgen Synthesis or Action
  
  • LH receptor mutations
  • forms of congenital adrenal hyperplasia
  • complete or partial androgen insensitivity
  • 5-alpha reductase deficiency

Question 9

What are the main features of complete androgen insensitivity syndrome?**

Answer 9

• 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

Question 10

What are the main features of partial androgen insensitivity syndrome?**

Answer 10

• 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 (?)

Question 11

Describe the chromosomal makeup, external and internal genitalia, and abnormalities of the genitalia in 5-alpha reductase deficiency.

Answer 11

• 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

Question 12

What are the major 46, XX DSD?

Answer 12

• 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
• Disorders of androgen synthesis
  
  • maternal virilizing tumors
  • congenital adrenal hyperplasia (CAH)
    
    • 21 hydroxylase deficiency
    • 11 hydroxylase deficiency
  • Placental aromatase deficiency

Question 13

Describe the chromosomal makeup, external and internal genitalia, and abnormalities of the genitalia in 21 hydroxylase deficiency.

Answer 13

• 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