Sex Determination

Question 1

What is an embryo described as before sex determination?

Answer 1

Bipotent or sexually indifferent

Question 2

When does sex determination begin?

Answer 2

<7 weeks gonadal ridges could develop into testes or ovaries
> 7 weeks gender development as determined by sex chromosomes

Question 3

Normal male sex determination?

Answer 3

1) Sry gene activates cascade of genes on autosomes and y involved in male development
2) testes development is initiated
3) testes release testosterone - leading to normal male development

Question 4

Normal female development >7 weeks

Answer 4

Not just absence of SRY- 2 x’s required for normal female development

Question 5

Gene involved in secondary dif- important for development of kidneysa and gonads?

Answer 5

WT1:11p13

Question 6

Location and role of SF1?

Answer 6

9q33

Steriodogenic factor 1

Question 7

Gene that is a transcription factor for gonadal development?

Answer 7

LHX9: 1q31-32

Question 8

Role and location of sox9?

Answer 8

17q24-25 required for male and female development. Mutations can lead to sex reversal

Question 9

Location and role of DAX1

Answer 9

Xq21- dosag sensitive sex reversal adrenal hyperplasia Critical region

Question 10

What is sex reversal?

Answer 10

When phenotypic sex and chromosomal sex differ

Question 11

What are the two causes of male sex reversal?

Answer 11

80% have unbalanced X-Y translocation so Y material (including SRY)on distal X
20% have no SRY and partial male/ambiguous sexual development

Question 12

Causes of sex reversal in females?

Answer 12

XY females usually carry a copy of the SRY gene and either
A) SWYER SYNDROME- a genetic mutation in Sry or other genes in development cascade
B) androgen insensitivity syndrome - sry working but have failure of response of an androgen receptor

Question 13

Symptoms of swyer syndrome/pure gonadal dysgenesis?

Answer 13

Streak gonads (mainly fibrous tissue)
Female external genitalia 
Failure of puberty
30% risk of developing gonadoblastoma (remove gonads in 1st decade of life)

Question 14

Symptoms of complete androgen insensitivity/ testicular feminisation?

Answer 14

Female external genitalia 
; short/absent vagina 
At puberty development of breasts 
Amenorrhea 
Intra abdominal testes
2-5% risk of gonadoblastoma

Question 15

Examples of androgen resistance syndromes?

Answer 15

5alpha-reductase

17alpha hydroxylase deficiency

Question 16

Symptoms of androgen resistance syndromes ?

Answer 16

46, XY karyotype
Bilateral testes and normal secretion of testosterone
Female external genetalia but virilisation of external genetalia at puberty
Male breasts
Reduced spermatogenesis

Question 17

What causes congenital adrenal hyperplasia (CAH)?

Answer 17

Enzyme deficiencies affecting steroidogenesis

Classic = 21- hydroxylase deficiency

Question 18

In utero- what’s the phenotype of XX and XY with CAH?

Answer 18

XX- masculinisation of external genetalia

XY- normal genetalia

Question 19

How do u treat CAH pregnancies? What’s the risk if untreated?

Answer 19

Treat with DEXAMETHASONE in utero and with hormones after birth
If untreated = salt-wasters. Can die in a few weeks

Question 20

How does autosomal sex reversal occur? Give an example?

Answer 20

Autosomal imbalance in regions carrying other genes in the male determining cascade- e.g deletion/ unbalanced translocation of 9q33 (SF1)

Question 21

Phenotype of autosomal sex reversal?

Answer 21

Female phenotype

Usually also mentally retarded and dysmorphic due to unbalanced karyotype

Question 22

What is associated with a 9p24 deletion?

Answer 22

Contains SRXY genes - sex reversal

Question 23

Deletions of 10q26.1

Answer 23

Genital abnormalities - most common cryptorchidism (testes undescended)

Question 24

What syndromes associated with 11p13 deletion?

Answer 24

Gene= WT1- associated with Wilma tumour, WAGR, Frasier syndrome, and Denny - crash syndrome

Question 25

Phenotype of translocation involving 17q24.3-q25.1

Answer 25

Sox9 gene

Compomelic dysplasia - skeletal abnormalities and death!!

Question 26

What could cause an XY female?

Answer 26

Duplication of Xp21 (DAX1 gene) - double dose of DAX1 disrupts testis development

Question 27

What is hermaphroditism?

Answer 27

Gonads comprise both ovarian and testicular elements

Ambiguous external genetialia

Question 28

What are the most common causes of hermaphroditism?

Answer 28

Most common. 46, XX (no Y chromosome)

Occasionally chimerism 46 xx/46 xy

Question 29

What are pseudohermaphrodites?

Answer 29

Have ambiguous genetalia and gonads of either

1) ovarian elements only = female hermaphrodite
2) testicular elements only = male pseudohermaphrodite