Disorders Of Sex development

Question 1

46,XY DSD

Ddx broad categories

Answer 1

Defects in testicular development

Deficiency of testicular hormones

Defect in androgen action

Question 2

46,XX DSD

Ddx broad categories

Answer 2

Androgen exposure

• fetal / fetoplacental source
• maternal source

Disorder of ovarian development

Question 3

What is needed to develop ovaries

Answer 3

46,XX
DAX1 on X chromosome
Signaling molecule on WNT-4
R-Spondin1

Question 4

What is needed for male phenotype

Answer 4

Y chromosome 
Intact SRY
SOX9
SF-1
WT1

Question 5

Mullerian ducts
Regress in presence of ….
If persist, become…

Answer 5

AMH
Uterus
Fallopian tubes
Cervix
Upper vagina

Question 6

Leydig cell start production of testosterone at ….. weeks

Stimulated by …..

Testosterone initiates development of…..

Answer 6

8 weeks

Placental hCG

Wolfian duct into epididymus, vas deferens, seminal vesicles

Question 7

Male external genitalia requires what hormones …

Action

Receptor required

Answer 7

Testosterone and Di hydro testosterone

Fuse genital folds

Two pathways to form DHY

• from circulating testosterone
• from androstanediol ( needed for complete prenatal virilisation)

Functional androgen receptor required (XL gene)

Question 8

Most common DSD

Answer 8

Virilisation of a female

Question 9

Most common forms of 46,XX

Answer 9

Virilising forms of CAH

Test 17-hydroxyprogesterone and androstenedione for 21- hydroxylase def

11-hydroxylase

Salt wasting more virilising

May present as bilateral cryptorchidism

Question 10

Defects in testicular differentiation

Syndromes and gene

Answer 10

Denys - Drash (WT1)

Fraser syndrome (WT1)

WAGR (del Ch 11p13- aniridia gene PAX6; WT1)

Campomelic syndrome
( SOX9, directly regulates COL2A1 )

Swyer: normal stature, female phenotype, hypergonadotrophic primary amenorrhea. Streak gonads. Mutation to SRY

Question 11

Defects in testicular hormones

What test required

Answer 11

Five genetic defects causing failure of enzymatic synthesis

And leydig cell aplasia

HCG stimulation test

Question 12

Defects in androgen action

Answer 12

DHT deficiency
Ambiguous external genitalia
Wolfian internal structures
Steroid a-reductase deficiency

Androgen insensitivity syndromes: most common XY DSD
CAIS: elevated LH infancy, testis found in herniorrhaphy; primary amenorrhea

PAIS: ambiguous genitalia , hypogonadism, gynaecomastia, severe hypospadias

Question 13

Smith-Lemli-Opitz
Inheritance
Defect
Features

Answer 13

AR
Sterol 7-reductase
Growth retardation, microcephaly, ptosis, syndactyly, severe cognitive impairment
Abnormal genitalia