16. Sex chromosome aneuploides

Question 1

What is the karyotype of Klinfelter syndrome?

Answer 1

Commonly 47,XXY

Also 48,XXYY; 48,XXXY; 49,XXXXY

Question 2

What causes Klinefelter syndrome?

Answer 2

Non-disjunction of one X during meiosis I (paternal) or meiosis II (maternal)

Question 3

What causes a more severe phenotype in KS? Why?

Answer 3

More severe phenotype with increased number of X chromosomes

Due to extra copies of genes on pseudoautosomal regions which escape X inactivation

Question 4

What is the recurrence risk of KS?

Answer 4

Not increased above general population risk

Question 5

What is the clinical phenotype of KS?

Answer 5

Hypogonadism, infertility, decreased endocrine function, speech delay, dev delay, gynaecomastia, small testes, tall stature

Question 6

What karyotypes cause Turner syndrome?

Answer 6

50% are 45,X

Also:
- 46,X,(delXp)
- 46,X,i(Xq)
- 46,X,r(x)

Question 7

In TS, who is the single X chromosome usually inherited from?

Answer 7

Mother

Due to non-disjunction in father (associated with increased paternal age)

Question 8

What is the clinical phenotype of TS?

Answer 8

Congenital ovarian hypoplasia = POF, streak gonads, infertility, hypergonadotropic hypogonadism

Short stature, webbed neck, skeletal abnormalities, heart defects

Frequently mosaic

Question 9

What phenotype is associated with mosaic Turner syndrome?

Answer 9

Milder phenotype with 45,X/46,XX

Question 10

What is the recurrence risk of TS?

Answer 10

Not increased in subsequent pregnancies

Question 11

What causes the skeletal abnormalities seen in TS?

Answer 11

SHOX important for bone development, located in PAR - loss of one copy results in short stature & skeletal abnormalities

Question 12

What causes a phenotype in trisomy X?

Answer 12

Over-expression of genes on X-chromosome that escape inactivation

Question 13

What is the phenotype of trisomy X?

Answer 13

Variable phenotype so under diagnosed

Tall stature, epicanthal folds, hypotonia, clinodactyly, seizures, POF, motor/speech delay

Question 14

What is the cause of trisomy X?

Answer 14

Usually due to meiotic non-disjunction, occasionally due to post-zygotic non-disjunction

Question 15

How are sex chromosome aneuploidies detected?

Answer 15

QF-PCR & confirmed by karyotyping - gives structural info and therefore info about recurrence

Often detected in adults following investigations for fertility

Question 16

What are the mosaic forms of trisomy X?

Answer 16

Mosaic in 10% of cases

1. 45,X/47,XXX
2. 46,XX/47,XXX
3. 47,XXX/48,XXXX