Pre-pubertal and Congenital Disorders

Question 1

Normal Male Development

Answer 1

Y chromosome has SRY gene which stimulates testes development. Testes produce 2 cells: Sertoli (AMH) and Leydig (testosterone). AMH causes regression of Mullerian ducts. Testosterone stimulates development of internal male genitalia: epididymis, seminal vesicles, vas deferens
Scrotal skin contains 5 alpha reductase which converts testosterone into more potent DHT which causes virilization of male external genitalia
Genital tubercle become glans penis, folds become scrotum

Question 2

Normal Female Development

Answer 2

Absence of SRY gene and AMH leads to development of ovaries, Mullerian ducts form uterus, fallopian tubes and upper 2/3 of vagina. No testosterone so no virilization. Lower third of vagina comes from urogenital folds.
Genital tubercle becomes clitoris, folds become labia

Question 3

Turner’s Syndrome

Answer 3

45 XO
Most common chromosomal anomaly in females
Short stature, neck webbing, wide carry angle
Associated with coarctation, IBD, SNHL, CHL
Ovary does not complete normal development, only stroma is present at birth
Ovary does not produce oestrogen or oocytes
Diagnosed at birth or childhood
Child: Growth
Puberty: Induction
Pregnancy requires ovum donation

Question 4

Swyer Syndrome

Answer 4

XY Karyotype
Complete gonadal dysgenesis
Gonad remains streak gonad
Does not produce hormones
Absence of AMH, Mullerian structures develop into female internal genitalia
Virilization does not occur due to lack of testosterone
Present at adolescence with pubertal failure
Dysgenic has high malignancy risk-removal laparoscopically
Induce puberty with oestrogen

Question 5

Mixed Gonadal Dysgenesis

Answer 5

Mosaicism might be present, if both functional ovarian and testicular tissue then ovotesticular DSD

Question 6

Complete Androgen Insensitivity Syndrome

Answer 6

Karyotype: 46 XY
X-Linked recessive
Inability of androgen receptor to respond to androgen
Have testes, Mullerian regression, testosterone production is normal
Breast development normal, pubic and axillary hair abnormal due to lack of androgen effects
Investigate: Karyotype and Pelvic US
Management: gonadectomy after puberty and long term-HRT
Vagina dilation for sexual function

Question 7

Partial AID

Answer 7

Typically diagnosed at birth with ambiguous genitalia

Question 8

5-a-reductase deficiency

Answer 8

Karyotype: XY
Normal functioning testes
Unable to convert testosterone to DHT
Present with ambiguous genitalia at birth
Increasing virilization at puberty due to high testosterone

Question 9

Congenital Adrenal Hyperplasia

Answer 9

Enzyme deficiency of 21-OH hydroxylase in classical CAH in corticosteroid pathway.
Less cortisol leads to negative feedback leading to adrenal hyperplasia leading increasing progesterone production and excessive androgen precursors and therefore testosterone
In XX individuals:
Virilization of External Genitalia, enlarged clitoris, fused labia and scrotal appearance
2/3 are also Salt wasting due to inability to produce aldosterone-dangerous
Need life-long steroid replacement with hydrocortisone and fludrocortisone
MDT management

Question 10

Mullerian Obstruction

Answer 10

Failure of complete canalisation of Mullerian strcutres leading to menstrual obstruction, commonly at junction of lower 1/3 vagina at level of hymen-transverse vaginal septae
Presents as imperforate hymen, increasing abdominal pain at menarche and retained blood leads to vaginal stretching causing haematocolpus, large pelvic mass seen as bulging membrane at vaginal entrance
Treat with surgical incision and drainage of blood

Question 11

Mullerian duplication

Answer 11

May be complete duplication of uterus, cervix and vagina or simply midline uterine septum with otherwise normal internal genitalia

Question 12

Mullerian agenesis

Answer 12

Absent or rudimentary uterus and upper vagina
Rokitansky syndrome
Normal ovarian function typically
Presents as primary amenorrhoea in presence of otherwise normal pubertal development
Can have own genetic children
Blind ending vagina

Question 13

Ethical Considerations

Answer 13

Duty to inform patients of diagnosis including karyotype
Move to reduce childhood surgical procedures
Protection against discrimination

Question 14

Gender Recognition Act

Answer 14

Allow people with Gender Dysphoria legal recognition as members of the sex appropriate for their gender