This document provides an outline on disorders of sex development (DSD). It discusses key terms, incidence, embryology, psychosexual development, classification, causes and evaluations of DSD. Ambiguous genitalia at birth can be a diagnostic dilemma for physicians. A multidisciplinary approach is needed to accurately diagnose and counsel parents on therapeutic options for conditions affecting sex determination.

1. Saleamlak T.( MD,Pediatric surgery Resident)
Oct, 2019

2. OUTLINES
 Introduction
 Terms
 Incidence
 Embryology
 Psychosexual development
 Classification and causes
 Evaluations
 Management
 Summary
 Reference

3. Introduction
 The birth of a new baby is one of the most
dramatic events in a family
 The first question is usually “is it a boy or a girl?”
 When a child is born with ambiguous external
genitalia
 It often comes as a surprise for the parents
 Diagnostic dilemma for the treating physicians
 It is also considered as an endocrine emergency situation presenting a
problem of sex assignment.
 It is important for clinicians to promptly make an accurate diagnosis
and counsel parents on therapeutic options

4. Terms
 In the past several names
 Intersex
 Hermaphrodite(hermaphroditism)
 Pseudohermaphrodite
 Sex reversal
 All the terms were replaced by the term
Disorders of Sexual Development (DSD)
 Coined by International Consensus Conference on Intersex
organized by
 The Lawson Wilkins Pediatric Endocrine Society and
 The European Society for Pediatric Endocrinology in 2006

5. Terms
 Disorders of sex development (DSD)
 Defined as congenital conditions in which development of
 Chromosomal , gonadal, or anatomical sex is atypical.
The three general descriptive terms to describe the sex of a person
 Genotypic
(Chromosomal sex):
 Gonadal sex:
 Phenotypic sex
Refers to the sex based on the number of sex chromosomes
Depends on the presence of 46,XX or 46,XY chormosomes
Refers to the sex according to the gonadal differentiation.
Depends on the presence of ovaries or testes and internal
genitalia
Refers to the sex based on the external anatomy of the
genitalia

7. Incidence
 DSDs are rare and complex
 It is estimated that the overall incidence of DSDs
 1 in 4,500–5,500 live births
 Congenital adrenal hyperplasia (CAH) and mixed
gonadal dysgenesis
 Are the most common causes of ambiguous genitalia
• Constituting approximately over 50 % of all cases of genital ambiguity
in the newborn period
 The incidence of
• CAH – 1:15,000 and
• Mixed gonadal dysgenesis – 1:10,000
 Currently, many countries screen newborns for CAH by use of
filter-paper blood spot 17-hydroxyprogesterone measurements

8. Embryology of Sexual Differentiation
 Normal sexual differentiation is based on the
genetic sex (XX or XY)
 Until 7th weeks
 Two undifferentiated bipotential gonads
 Two pairs of internal ducts (whether the fetus is female or male)
• The Wolffian ducts
• The Müllerian ducts
 At about 7weeks ( Gonadal differentiation)
 The indifferent gonads and in the presence of a Y chromosome
• Begin to develop into testes
 The indifferent gonads and in the absence of a Y chromosome
• Begins to develop into ovaries

10. Gonadal Differentiation

11. Internal Genitalia Differentiation

12. External genitalia

14. Psychosexual Development
Three stages:
Gender labeling- 18months
Gender constancy- 3yrs
Gender stability – 4-5yrs
Three components :
Gender identity
Self recognition as a boy or a girl
Gender role:
Sex-typical behaviors
Sexual orientation
The direction(s) of sexual interest
Factor affect psycosexual dev’t:
 Androgen exposure
 Sex chromosome genes and
brain structure
 The society and family
perspectives
 Gender dysphoria
 Indicates unhappiness with the assigned sex
 It results from an inconsistency between the assignment and the
inherent identity later in life

15. Classification
 2006 Chicago consensus( ESPE and
LWPES)
 DSD can be classified into 3 diagnostic Groups
( based on the peripheral blood karyotype)
1. 46XY DSD
2. 46XX DSD
3. Sex chromosome aneuploidy DSD
a. 47,XXY- Klinefilter syndrome
b. 45, X – Turner syndrome
c. 45,X/ 46, XY- Mixed Gonadal Dysgenesis
d. 46XX/ 46XY- Mosaicism

16. 46,XX DSD (Androgenized Females) , Prev.
Female pseudohermaphroditism
 Defn.
 Virilisation of external genitalia of a 46,XX female
 Intrauterine exposure to androgens at critical phase of
differentiation
 From mild clitoromegaly to a normal male appearance
 Sources
 Adrenal- CAH( 95%)
 Testicular - O-T DSD with 46xx karyotype
 Maternal
 Ingestion of drugs, or
 Androgen secreting tumors
 Presentation
 Ambiguous external genitalia
 Phallic enlargement, Labial fusion
 Normal internal genitalia(Ovaries, Fallopian tubes, Uterus,Cervix
& Upper vagina)
 Later age
 Gradual enlargement of clitoris- Nonclassic CAH

17. Congenital Adrenal Hyperplasia
 The commonest cause of genital
ambiguity at birth
 Inability of the adrenal gland to
produce cortisol
 Due to deficiency of steroidogenic
enzymes
 21 -hydroxylase deficiency(95%)
• Type 1- non salt wasting- 25%
• Type2 – salt wasting – 75%
 11 beta-hydroxylase deficiency
 3ß-hydroxysteroid dehydrogenase
deficiency
 Diagnosis
 Serum 17OH-progesterone (21OHase)
 Serum deoxycorticosterone (11OHase)
Treatment
Medical management
Fluid and electrolyte replacement
Hydrocortisone
Fluorohydrocortisone
Surgical management
Clitoroplasty
Labioplasty
Vaginoplast

18. 46 XY DSD (Unandrogenized males) prev. male
pseudohermaphroditism
Failure to produce testosterone
 Pure XY gonadal dysgenesis
(Swyer’s syndrome)
 Anatomical testicular failure
(testicular regression syndrome)
 Leydig-cell agenesis
 Enzymatic testicular failure
Failure to utilize testosterone
 5-alpha-reductase deficiency
 Androgen receptor deficiency
 Complete androgen insensitivity
syndrome(CAIS)
 Incomplete androgen Insensitivity(PAIS)
Ambiguous or
Female external genitalia

19. Swyer syndrome
46, XY
No SRY OR its receptors
STREAK GONADS
- NO MIF (Uterus +)
- NO SEX STEROIDS
Female Internal
Genitalia
Female external
Genitalia

20. Testicular regression syndrome
(congenital anorchia)
46-XY/SRY
Testis  MIF
(self destruction))
± testosterone
± DHT
± Male
Internal
genitalia
Female or
ambiguous
External
genitalia

21. Leydig-cell agenesis
46-XY/SRY
TESTIS  MIF
( partial/ complete absence
Of leydig-cells)
No or  testosterone
No or  DHT
 ± Male Internal
Genitalia
 Female or
 ambiguous
external
Genitalia

22. Testicular enzymatic failure
46-XY/SRY
Testis  MIF
(defects in testosterone Synthesis)
 testosterone precursors
DHT
Male Internal GenitaliaAmbiguous
External
Genitalia

23. 5-alpha-reductase deficiency
46-XY/SRY
Testis  MIF
Testosterone
**5--rductase
Male Internal
Genitalia
Female or
Ambiguous
external Genitalia
DHT

24. Androgen Insensitivity Syndrome
46-XY/SRY
TESTIS  MIF
Testosterone
5--reductase
DHT
**Absent or insensitive androgen
receptors
Male Internal Genitalia
Female External Genitalia
Incomplete form  Ambigious genitalia

25. Sex chromosome DSDs:
 Sex chromosome DSD
 Formerly termed as gonadal dysgenesis
 If a testis is poorly formed
• It is called a dysgenetic testis
 If an ovary is poorly formed
• it is called a streak gonad
 A patient with a Y chromosome is at high risk of developing a
tumor in a streak or dysgenetic gonad
 Mixed gonadal dysgenesis
 2nd most common cause of ambiguous genitalia
 Ovotesticular DSD
 Partial gonadal dysgenesis
 Pure gonadal dysgenesis

26. The Prader Scale

27. The Prader Scale Of Genitalia
 Stage 0
 Normal female genitalia.
 Stage 1
 Mildly enlarged clitoris, slightly reduced vaginal opening.
 Stage 2
 phallus being intermediate in size, small vaginal opening with separate urethral
opening. Posterior labial fusion present.
 Stage 3
 Further enlarged phallus than Stage 2, with single urogenital sinus and nearly
complete fusion of the labia.
 Stage 4
 looks more male than female, with an empty scrotum and a normalsized penis-like
phallus
 A small urethral/vaginal opening at the base of the shaft/phallus (hypospadias in a
male).
 Stage 5
 This is complete male virilisation – a normally-formed penis is present, with the
urethral opening at or near the tip, and the scrotum formed, but empty.
 Stage 6

28. Evaluation of a Newborn with DSD

29. Evaluation of a Newborn with DSD
 The evaluation, diagnostic approach and management of a newborn
with DSD involves a multidisciplinary team approach.
 This team include:
 Neonatologists
 Geneticists/genetic counselor
 Pediatric endocrinologists
 Pediatric surgeons
 Social worker
 Pediatric urologist
 Psychologist

30. The Neonate with Ambiguous Genitalia
 Diagnostic Rules and Clinical Significance
1. Testes descend (through the abdominal wall and down to the scrotum), but ovaries
do not Federman’s rule
 Federman’s rule:– a gonad felt below the inguinal ligament is a testicle until proven otherwise
2. Testicular descent is tightly linked to Müllerian duct regression
3. The presence of the uterus (on digital examination or ultrasonography)
4. Regulation by male hormones of the internal genitalia is exocrine or paracrine
5. Circulating androgens from an abnormal adrenal gland or other sources are
insufficient to allow development of the male internal genitalia
6. External virilisation is directly proportional to the amount of androgens
7. The degree of external masculine development is inversely proportional to the
degree of lower vaginal development
8. Circulating androgens only masculinise the external genitalia (except for the
phallus) between 8 and 12 weeks of development
9. Use of the word ‘ hypospadias’ assumes the affected infant is a boy, and should
only be diagnosed at birth (without investigation) when both testes are fully
descended into a fused scrotum
10. Genital anomalies may be caused by non-endocrine mechanisms

31. Ambiguous Genitalia
 Apparent female genitalia
 Enlarged clitoris
 Posterior labial fusion
 Inguinal or labial mass
 Apparent male genitalia
 Bilateral nonpalpable testes
 Micropenis
 Isolate perineal hypospadias
 Mild hypospadias with UDT
 Family hx of DSD
 Genital and karyotype discordance

32. Local examination
External genitalia
 Present or absent
If present:
Male/ female component
Male component:
Phallus:
Size
Measure Stretched penile length(normal
> 2.5cm)
Site of urethral opening
Scrotum:
Skin , pigmentation, bifid
Palpate testis :
volume, inguinal region( NP)
 Female component:
Labia majora / minora
Posterior labial fusion
Urethral opening, vaginal
opening
clitoris : Measure(N < 1cm)
Gonads
Palpate inguinal region and labia majora
Per rectal examination – uterus
 Anogenital ratio

33. The Prader Scale

34. Investigations
 Karyotyping
 The serum electrolytes, glucose and 17-
OH progesterone
 To assess gonadal function
 Serum testosterone (Leydig cells), FSH, LH (pituitary),
and MIS/AMH (Sertoli cells)
 The serum ratio of testosterone/DHT
 DIAGNOSTIC TESTS
 hCG-stimulation test
 ACTH stimulation test
 Testosterone Trial test

35. Imaging and surgical work up
 Imaging
 Abdominal and Pelvic ultrasonography
 Detect the neonatal uterus
 Demonstrate the location of intra-abdominal gonads
 Assess the urinary tract
 CAH
 Urogenital sinugram( Genitogram)
• Confirm the presence of and delineate the anatomy of the lower
vagina
 Endoscopy
• The contrast X-ray fails to demonstrate a vaginal opening
 Laparoscopy
 Gonadal biopsy
 Genital skin biopsy

39. Unsuspected cases
If you get the testes while operating the female child with herniotomy, what do you do?
If the child has CAIS, is that possible to suspect preoperatively?
 Take a picture for documentation
 Take gonadal biopsy
 Replace them within the abdomen
 Complete inguinal herniotomy
 Gonadal excision left to later date
 Abnormal growth of testes
 Palpation of the enlarged gonad in
the hernial sac

40. DSD Later in Childhood

41. How to put a Proper Diagnostic Documentation?
Prefixed : by karyotype
 Followed: by Gonadal morphology or diagnostic group
 Ended : by phenotype anatomy(using recognized
pictoral scale- as Prader Scale)
Eg.
A neonate with ambiguous
genitalia due to PAIS
46, XY, PAIS, Prader 3
Eg.
A neonate with highly virilised
genitalia genitalia due to CAH
46, XX, CAH, Prader 5

42. Management of DSD
 Initial evaluation
 Medical evaluation as soon as possible
 Sex assignment
 Crisis for the parents
 Avoid referring as “she”, “he” even “it”
 This is the defining step in management of a child with a DSD
 The decision on the sex of rearing should be delayed until
 A precise diagnosis has been established
 The likely functional potential of the genitalia has been adequately
assessed
1) The phenotype
2) The appearance of the genitals
3) The surgical options
4) The need for future hormonal replacement therapy
5) The potential for future fertility
6) The culture and preferences of the family
7) The effect of high levels of testosterone exposure on the brain development
What are the factors that must be considered during sex assignment?

43. Sex assignment(Principles)
 46,XX,DSD
 Mostly virilized female with CAH
 Assigned as female
 Exceptional
• Late presentation with established male identity
 46, XY,DSD
 Female gender assignment- advised
 External genitalia- predominantly or entirely female
 Male gender assignment
 Significant male phenotype
 Stimulation test indicates responsiveness to androgen
 MGD and O-T DSD
 Size of the phallus and the potential for androgen production
 Male or female
 MIS deficiency or receptor insensitivity
 Male assignment
 5-alpha-reductase deficiency
 Assigned a male sex, Fertility is preserved.
Cultural considerations upon the decision regarding sex of rearing
Eg. highly virilised 46xx DSD.

44. Surgical Management of DSD
 Feminising genitoplasty
 Clitoroplasty
 Labioplasty
 Vaginoplasty
 Masculinising genitoplasty
 Orchidopexy
 Repair of hypospadias with chordee correction
 Excision of retained Müllerian duct structures
 Phalloplasty???
 Penile transplantation???????????????
 Gonadal excision

45. Timing of surgery
 During infancy Vs Later time
 AAP Guideline
 Feminizing genitoplasty
• During the first 6 months of life
 The optimum timing for masculinising genitoplasty
• Is between the ages of 6 and 18 months

46. Feminising Genitoplasty
 The surgical repair of infants being raised as
females includes the following principles:
1. Reduction of the erectile tissue of the enlarged phallus
 With preservation of the glans and its neuro-vascular supply
2. Creation of a normal looking introitus
 With labia minora and labia majora
3. Vaginoplasty
 To provide an adequate opening in the introitus for the vagina

47. Clitoroplasty
 Historical
 Until 1960
 The principal surgical procedure to manage enlargement
clitoris was excision of the clitoris or clitoridectomy
 1960s and 1970s
 Bury the clitoris in the mons
• Preserved neurovascular supply and function, and
• Produced a good cosmetic effect in early childhood
 But led to painful erection during sexual arousal in adult life
 Reduction clitoroplasty
 Part of the erectile tissue was removed with preservation of
the glans and neurovascular bundles

48. Clitoroplasty

50. Cliteroplasty

51. Vaginal reconstruction techniques
 Cut-back vaginoplasty
 Is rarely used and is appropriate for only simple labial fusion.
 Flap vaginoplasty
 Applicable to a low (distal) vaginal confluence
 In this procedure, the posterior walls of the sinus and vagina are opened
 But the anterior wall of the vagina is left intact.
 Pullthrough vaginoplasty
 Is used for a very high confluence
 Total and partial urogenital mobilization (TUM and PUM)
 Complete vaginal replacement
 Can be achieved by several techniques
 But it is used only for a rudimentary or absent vagina.

53. Masculinizing Genitoplasty
 Phalloplasty:
 Currently
 There is no tissue available to increase the size of an underdeveloped
phallus
 In patients with DSD associated with hypospadias
 The complexity of this procedure must be discussed with the parents
during the initial counseling
 The standard surgical repair include:
 Increase penile size and length with topical or injectable testosterone
 Chordee correction
 Repair of hypospadias

55. Gonadectomy:
 Time
 Controversy regarding the timing of gonadectomy
 Some recommended that gonadectomy should be performed soon after
diagnosis
• Because estrogen-replacement therapy could be started
 Others prefer delayed gonadectomy with the advantages of late
gonadectomy include
• Breast development
• Avoidance of poor adolescent compliance with estrogen- replacement therapy
 Indications
 Germ cell malignancy
 In patients with androgen biosynthetic defects raised who are
raised as females
 A scrotal testis in patients with gonadal dysgenesis

56. Medical and psychotherapy:
 Hypogonadism is common in patients with:
 Dysgenetic gonads
 Defects in sex-steroid biosynthesis
 Resistance to androgens
 Hormone-replacement therapy is often required
in patients with DSD to:
 Induce and sustain puberty
 Induce secondary sexual characteristics
 Induce pubertal growth spurt
 Optimize bone mineral accumulation
 Help with psychosocial maturation

57. Medical and psychotherapy:
 Boys with hypogonadism
 Require intramuscular injections of
 Either testosterone cypionate or ethanate for pubertal induction
 Other testosterone preparations
 Such as gels and patches are also available.
 In girls with hypogonadism
 Estrogen supplementation to induce secondary sexual changes
and menstruations is required
 Estrogen can be given orally, by injection, or patch.
 A progestin is usually added after breakthrough bleeding develops or
within 1–2 years of continuous estrogen.

58. Medical and psychotherapy:
 Psychosocial care
 Should be an integral part of the management of patients with
DSD to promote positive adaptation
 Families and individuals require ongoing counseling by
experienced personnel
 Other important resources include
 Access to confidential sexual counseling and support groups
 Regular follow-up from infancy to adulthood is important
 Sexual
 Psychological and
 Social parameters is important

59. Summary DSD is a congenital condition characterised by atypical development
of the three character of sex
 Management of infants suffering from DSD is challenging
 Especially in Africa and developing countries due to educational, financial, and
behavioural factors
 Cases should be managed through a multidisciplinary team
 No assignment should be offered before full work-up, and
 reassignment should be considered in some cases
 Surgical correction should be based on anatomical and functional
bases rather than a cosmetic one
 Early correction is advised in congenital adrenal hyperplasia
 Gonadectomy should be performed in cases at high risk to develop
gonadal carcinoma as well as in cases suffering gonadal dysgenesis or
PAIS with intraabdominal gonads
 Psychosocial care should be an integral part of the management of
patients with DSD

60. References
 Coran Pediatric Surgery, 7th ed
 Disorders of Sex Development, An Integrated Approach to
Management, John M. Hutson • Garry L. Warne • Sonia R.
Grover,2012
 The Kelalis-King-Belman Textbook of Clinical Pediatric Urology
Informa 2007.
 Essentials of pediatric urology 2nd, 2008
 Pediatric surgery :a comprehensive text for Africa(volume II)
 AAP guideline
 Journals

61. 6
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