brief ,illustrated presentation about disorder of sex development in paediatrics

1. Presented by:
Dr. Mona
Mohammed Ali

2. Introduction:
Disorders of sex development (DSDs),
formerly termed intersex conditions, are
seen in infants who are born with
ambiguous or abnormal genitalia and may
have indeterminate phenotypic sex.

3. Classification:
 In 2006, the Lawson Wilkins Pediatric Endocrine Society
(LWPES) and the European Society for Pediatric
Endocrinology (ESPE) published new classification.
Previous Term Revised Term
Female pseudohermaphrodite 46,XX DSD
Male pseudohermaphrodite 46,XY DSD
True hermaphrodite Ovotesticular DSD
XX male 46,XX testicular DSD
XY sex reversal
46,XY complete gonadal
dysgenesis

4. As examples, classifications of sex
chromosome DSD include the following:
1. 45,X ( Turner syndrome and variants)
2. 47,XXY ( Klinefelter syndrome and variants)
3. 45,X/46,XY (mixed gonadal dysgenesis,
ovotesticular DSD)
4. 46,XX/46,XY (chimeric, ovotesticular DSD)

5. Classifications of 46,XY DSD include the
following:
1. Disorders of testicular development (complete and
partial gonadal dysgenesis)
2. Disorders of androgen synthesis (complete and
partial androgen insensitivity, disorders of
antimüllerian hormone [AMH]/receptor, androgen
biosynthesis defect)
3. Other (severe hypospadias, cloacal exstrophy

6. Classifications of 46,XX DSD include the
following:
1. Disorders of ovarian development
(ovotesticular DSD, testicular DSD, gonadal
dysgenesis)
2. Androgen excess (fetal [eg, congenital
adrenal hyperplasia (CAH)], fetoplacental,
maternal)
3. Other ( vaginal atresia, cloacal exstrophy)

7. History:
 Evaluation of a newborn with ambiguous genitalia requires a team effort.
 The most common disorder of sex development (DSD), congenital adrenal hyperplasia (CAH),
results in virilization of a 46,XX female and thus is classified under the heading of 46,XX DSD.
 The clinician's challenge is to distinguish CAH from other, less common causes of ambiguous
genitalia. A detailed family history is essential; the following considerations should be kept in
mind:
1. A family history of genital ambiguity, infertility, or unexpected changes at puberty may
suggest a genetically transmitted trait .Recessive traits tend to occur in siblings, whereas X-
linked abnormalities tend to appear in males who are scattered sporadically across the
family history
2. A history of early death of infants in a family may suggest a previously missed adrenogenital
deficiency
3. Maternal drug ingestion is important, particularly during the first trimester, when virilization
may be produced exogenously in a gonadal female
4. Although extremely rare, a history of maternal virilization may suggest an androgen-
producing maternal tumor (arrhenoblastoma)

8. Physical Examination:
 Certain physical characteristics may suggest the directions toward
which a successful investigation might be pursued.
 Examination of the external genitalia should include the following:
1. Note the size and degree of differentiation of the phallus, since
variations may represent clitoromegaly or hypospadias
2. Note the position of the urethral meatus
3. Labioscrotal folds may be separated or folds may be fused at the
midline, giving an appearance of a scrotum .
 Labioscrotal folds with increased pigmentation suggest the possibility
of increased corticotropin levels as part of adrenogenital syndrome

9. Physical Examination:
 Gonadal examination should include the following:
1. Documentation of palpable gonads is important; although ovotestes have been
reported to descend completely into the bottom of labioscrotal folds, in most
patients, only testicular material descends fully.
 If examination reveals palpable inguinal gonads, diagnoses of a gonadal
female, Turner syndrome, and pure gonadal dysgenesis can be eliminated
 Impalpable gonads, even in an apparently fully virilized infant, should raise the
possibility of a severely virilized 46,XX DSD patient with CAH.
 Rectal examination should include the following:
1. Rectal examination may reveal the cervix and uterus, confirming internal müllerian
structures
 The uterus is relatively enlarged in a newborn because of the effects of maternal
estrogen, permitting easy identification

10. Differential Diagnosis:
1. 3-Beta-Hydroxysteroid
Dehydrogenase Deficiency
3. 5-Alpha-Reductase Deficiency
5. Androgen Insensitivity Syndrome
7. Congenital Adrenal Hyperplasia
9. Denys- Drash Syndrome
11. Gender Identity
13. Genital Anomalies
15. Precocious Puberty
2. Gonadoblastoma
4. Hypogonadism
6. Hypospadias
8. Menstruation Disorders in
Adolescents
10. Microphallus
12. Paediatric Hydrocele and Hernia
Surgery
14. Paediatric Hypopituitarism
10

11. Workup:
Lab tests:
 A logical workup in infants with ambiguous genitalia
includes the following:
1. Chromosomal analysis
2. Endocrine screening
3. Serum chemistries/electrolyte tests
4. Androgen-receptor levels
5. 5-Alpha-reductase type II levels
6. Antimüllerian hormone (AMH)/müllerian-inhibiting substance
(MIS) level

12. Workup:
 Renal/bladder ultrasonography (US). . In a neonate, ambiguous
genitalia, enlarged adrenal glands, and evidence of a uterus are
virtually pathognomonic for CAH.
 Genitography helps determine ductal anatomy.
 Computed tomography (CT) and magnetic resonance imaging
(MRI) are usually not indicated but may help identify internal
anatomy.
 Cystourethroscopy.
 Open exploration, though rarely used nowadays, Laparoscopy
under general anesthesia to identify the exact anatomy and biopsy
the gonads

13. Management:
 Approach Considerations
 Factors to consider when planning for definitive management
of disorders of sex development (DSDs) include the following:
1. Phenotype
2. Functional potential of the external and internal genitalia
3. Tumor risk of the gonads
4. Fertility potential
5. Psychosexual issues (gender identity and sexual orientation)

14. Medical Care:
• Medical therapy for DSDs depends on the
underlying cause and is indicated for the conditions
associated with ambiguous genitalia,
including congenital adrenal hyperplasia (CAH).
• Supplemental hormone therapy may be
implemented if gonadal function is compromised.

15. Surgical Care:
There remains considerable controversy
surrounding the treatment of DSDs.
In a virilized female, the surgical procedure is
termed feminizing genitoplasty and includes
vaginoplasty, labiaplasty, and clitoroplasty (see the
images below).
The optimal timing of feminizing genitoplasty has not
been determined.

16. Patient with congenital adrenal hyperplasia
(CAH; 46,XX DSD). Note phalluslike clitoris and
empty scrotal appearance of labia majora.
Same patient with congenital adrenal hyperplasia
(CAH; 46,XX DSD), after feminizing genitoplasty
surgery. Note achievement of three components of
surgery: clitoroplasty, vaginoplasty. and labiaplasty.
Upper catheter is in urethra

17.  Undervirilized males typically have hypospadias requiring
surgical reconstruction.
 The limited data available on the timing of reconstructive
hypospadias surgery derive mainly from reconstructive
studies and expert opinion; until more and better data
become available, it may be reasonable to advocate early
surgery, between the ages of 6 and 18 months.
 Gender reassignment may be considered in patients with
46,XY DSD and genital inadequacy.
Surgical Care:

18. Consultations:
The following consultations may be obtained:
1. Genetics/genetic counseling
2. Endocrinology
3. Pediatric gynecology
4. Pediatric urology
5. Psychology
6. Social work

19. THANKS