Credits

• Section Writer: Dr. Om J Lakhani
• Section Editor: Dr. Om J Lakhani

Q. What is DSD ?

• Disorder of Sexual differentiation

Q. What features are considered atypical genitalia at birth ?

• Male type
  • Bilateral absent testis
  • Micropenis
  • Perineal hypospadias
  • Bifid scrotum
• Female type
  • Palpable gonads in labioscrotal folds
  • Clitoromegaly
  • Posterior labial fusion

Q. Which tests are sent immediately when you have a child with Atypical genitalia ?

• Karyotype with FISH for SRY
  • 17 OHP
  • Cortisol
  • Electrolytes
  • Pelvic abdominal USG

Classifications of DSD

Q. What are the three types of DSD ?

• XY DSD
• XX DSD
• Sex chromosome DSD

Q. What is another classification of DSD ?

• Malformative DSD – Abnormal morphogenesis of urogenital primordia
• Dysgenetic DSD- Abnormal gonadal differentiation
• Non Dysgenetic DSD- Abnormal sex hormone steroidogenesis

Q. What are causes of Malformative DSD ?

• Abnormal development of external genitalia
• Isolated micropenis
• Isolated hypospadias
• Abnormal development of internal genitalia
• MRKH
• Absent vas deferens – cystic fibrosis

Q. What are causes of Dysgenetic DSD ?

• Complete gonadal dysgenesis
• Partial gonadal dysgenesis
• Mild gonadal dysgenesis
• Asymmetric gonadal differentiation – ovotesticular DSD

Q. What are causes of complete gonadal dysgenesis ?

• Turner syndrome
• 46 XX gonadal dysgenesis
• WNT4 and RSPO1
• 46 XY gonadal dysgenesis
• Mutation in transcription factors – WT1, SRY SOX9, SF1, DHH, ATRX
• Chromosomal abnormalities- Yp deletion, 9q deletion (DMRT1), XP duplication

Q. What are causes of partial gonadal dysgenesis ?

• Same causes which cause complete GD can cause partial GD also
• Environmental factors- Endocrine disruptors
• Mosaic Turner

Q. What are causes of mild gonadal dysgenesis ?

• 46 XX male – transfer of SRY on X chromosome
• Klienfelter’s syndrome

Q. What are causes of ovotesticular DSD ?

• Mosaic sex chromosomes
• 46XY/45 X
• 46XY/46 XX

Q What are causes of Non dysgenetic DSD ?

• 46 XY
  • Abnormal testosterone biosynthesis pathway defect
  • Androgen receptor defect- Androgen insensitivity syndromes
  • Abnormality in AMH production or action- Persistent Mullerian Duct syndrome
• 46 XX
  • Virilizing CAH
  • Placental aromatase defect
  • Maternal virilization
  • Iatrogenic Androgen exposure

Q. Which are the Virilizing CAH in 46 XX ?

• 21 hydroxylase
• 3 beta HSD
• 11 beta-hydroxylase
• P450 oxidoreductase

Q. What are the causes of 46 XX DSD ?

• Malformative DSD- MRKH
• Dysgenetic DSD
  • Turner syndrome / Mosaic Turner
  • 46 XX male – SRY translocation to X
  • Complete gonadal dysgenesis – WNT4, RSPO1 defect
  • Ovotesticular DSD
• Non dysgenetic DSD
  • CAH
    • 21 hydroxylase
    • 3 beta HSD
    • 11 beta-hydroxylase
    • P450 oxidoreductase
  • Placental aromatase defect
  • Maternal virilization
    • Adrenal tumor
    • Ovarian tumor
    • Glucocorticoid resistance syndrome
    • Maternal virilizing CAH
  • Iatrogenic /environmental androgen exposure

Q. Enlist the causes of 46 XY DSD ?

• Malformative DSD
  • Isolated hypospadias
  • Isolated micropenis
  • Absent Vas deferns- Cystic fibrosis
• Dysgenetic DSD (gonadal dysgenesis)
  • Complete gonadal dysgenesis – SRY, WT1, SOX9, DHH, SF1
  • Partial gonadal dysgenesis – above in milder form
  • Mild GD – Kleinfetler’s syndrome
  • Ovotesticular DSD
  • Testicular regression syndrome
• Disorder of testosterone synthesis
  • LH receptor mutation
  • Smith Lemli Opitz
  • StAR defect
  • Sidechain cleavage enzyme defect
  • 17 alpha-hydroxylase defect
  • 17, 20 lyase defect
  • P450 oxidoreductase
  • 3 beta HSD defect
  • 17 beta HSD3 defect
  • 5 alpha reductase defect
• Disorder of androgen receptor
  • CAIS
  • PAIS
  • AMH defect
  • Persistent Mullerian duct syndrome