This document discusses disorders of sexual development (DSDs). It begins by defining DSDs as conditions where chromosomal, gonadal, or anatomical sex is atypical, often presenting as ambiguous genitalia. It then discusses the physiology of typical sexual development and classifies common types of DSDs. It provides examples of clinical features, diagnostic considerations, and genetic and gonadal characteristics for different DSD types, including 21-hydroxylase deficiency, gonadal dysgenesis, ovotesticular DSD, and partial androgen insensitivity. Images are included to illustrate some clinical presentations. The document emphasizes the importance of karyotyping and hormonal testing to diagnose DSDs.

1. APPROACH TO CHLID
WITH DISORDER OF
SEXUAL
DEVELOPMENT
DR. SACHIN SONI
DNB PEDIATRICS

2. What is DSD
• A condition “In which development of chromosomal, gonadal or
anatomical sex is atypical”
• Atypical or ambiguous genitalia- Any case in which the external genitalia
do not appear completely male or completely female
• Standards for genital size dimensions, variations in size of these
structures do not always constitute ambiguity

3. • Physiology of sexual development
• Testis-determining factor differentiation is visible by the 4th week of gestation
XY karyotype XX karyotype
7th week of gestation
Functional Leydig Functional Sertoli cells

5. Sexual differentiation and the development of internal and
external genitalia

6. Disorders of sexual development
classification

7. 21-OH
DEFICIENCY*
GONADAL
DYSGENESIS
WITH Y
CHROMOSOME
OVO
TESTICULAR
DSD
PARTIAL
ANDROGEN
INSENSITIVITY
BLOCK IN
TESTOSTERONE
SYNTHESIS
CLINICAL FEATURE
Palpable gonad − +/− +/− + +
Uterus present + + Usually − −
Increased skin
pigmentation
+/− − − − −
Sick baby +/− − − − +/−
Dysmorphic
features
− +/− − − −

8. 21-OH
DEFICIENCY*
GONADAL
DYSGENESIS
WITH Y
CHROMOSOME
OVO
TESTICULAR
DSD
PARTIAL
ANDROGEN
INSENSITIVITY
BLOCK IN
TESTOSTERONE
SYNTHESIS
DIAGNOSTIC CONSIDERATIONS
Serum 17OHP Elevated Normal Normal Normal Normal
Electrolytes
Possibly
abnormal
Normal Normal Normal
Possibly
abnormal
Karyotype 46,XX
45,X/46,XY or
others
46,XX 46,XY 46,XY
Testosterone
response to hCG
NA Positive
Normal or
reduced
Positive response
Reduced or
absent
Gonadal biopsy NA Dysgenetic gonad Ovotestis
Normal testis
with
Normal testis

9. Diagnostic tests
• 1. Karyotype, with rapid determination of sex chromosomes
( within 24-48 hours)
• 2. Other blood tests:- a- Screen for congenital adrenal hyperplasia: Cortisol
adrenal androgens- 17-hydroxyprogesterone and androstenedione for 21-
hydroxylase deficiency
b- Screen for androgens and their biosynthetic precursors
c- Screen for gonadal response to gonadotropin in patients suspected of
having testicular gonads: stimulation with injections of HCG; measure
testosterone and dihydrotestosterone before and after HCG
d- Molecular genetic analyses for SRY (sex-determining region of the Y
chromosome) and other Y-specific loci
e- Gonadotropin levels

12. Gonadal and chromosomal characteristics of
DSD

13. 46,XX DSD
• Previously known as female-pseudohermaphrodites
• Most common forms of 46,XX DSD are virilizing forms of congenital
adrenal hyperplasia (CAH)
• Normal ovaries
• Internal female organs are present
• Variable degrees of virilisation of the external genitalia

14. A 6-yr-old girl with congenital virilizing adrenal hyperplasia. The height age was
8.5 yr, and the bone age was 13 yr

16. - Complete masculinisation
- Normal looking
hyperpigmented male
genitalia
(but no palpable testes)
A 46,XX patient known to
have congenital adrenal
hyperplasia due to 21 α-
hydroxylase deficiency

17. Pigmented, short, curved
phallus, central urogenital
slit,
and separated labioscrotal
testis
A 46,XY patient known to
have congenital adrenal
hyperplasia due to 3β-hydroxy
dehydrogenase deficiency

18. - Micropenis
- Underdeveloped scrotum
- Bilateral undescended testes
A 46,XY patient known to have
gonadotrophin hormone
deficiency

19. 5α-Reductase deficiency
Boys with a small phallus
Bifid scrotum
Urogenital sinus with
perineal hypospadias, and a
blind vaginal pouch

20. Androgen Insensitivity Syndromes
Partial androgen insensitivity with
descended testes in bifid labioscrotal folds
Less severe partial androgen insensitivity with
severe hypospadias and maldescent of testes

21. • X-linked recessive disorders is due to mutations in the androgen receptor
gene
• 46,XY chromosomal complement- Phenotypic females (in complete AIS)
to males with various forms of ambiguous genitalia and undervirilization
(partial AIS, or clinical syndromes such as Reifenstein syndrome) to
phenotypically normal-appearing males with infertility
• Presence of testes and normal or elevated testosterone and LH levels are
common to all children

22. • Complete AIS- Extreme form of failure of virilization
• Genetic males appear female at birth
• External genitalia are female, vagina ends blindly in a pouch, uterus is
absent due to normal production and effect of AMH In about one third of
patients, Unilateral or bilateral fallopian tube remnants
• Testes are usually intra-abdominal but may descend into the inguinal canal,
they consist largely of seminiferous tubules
• At puberty normal development of breasts, and the habitus is female, but
menstruation does not occur and sexual hair is absent.
• Adult heights of these women are commensurate with those of normal
males despite profound congenital deficiency of androgenic effects

23. • Normal male levels of testosterone and DHT
• Failure of normal male differentiation during fetal life
• Defective response to androgens, absence of androgenic effects is caused by a
striking resistance to the action of endogenous or exogenous testosterone at the
cellular level
• Partial AIS- Perineoscrotal hypospadias, bifid scrotum, and cryptorchidism to
extreme under virilization appearing as clitoromegaly and labial fusion
• Reifenstein syndrome- Incomplete virilization characterized by hypogonadism,
severe hypospadias, and gynecomastia
• Gilbert-Dreyfus and Lubs are additional syndromes

24. A 46,XY patient known to
have partial androgen
insensitivity
• Micropenis,
• Urogenital sinus
• Labioscrotal folds
(the left fold contains a
palpable gonad)

25. Partial androgen
insensitivity syndrome at
adolescence
Gynecomastia from
peripheral aromatase
conversion of testosterone to
estrogen
Abundant pubic hair implies
only partial resistance

26. Ovotesticular disorder
Both ovarian and testicular
tissues are present

27. THANK YOU