Chromosome Disorders

Question 1

Give some examples of chromosomal abnormalities

Answer 1

• polyploidy (e.g. Triploidy)
• autosomal trisomies (13, 18, 21)
• sex chromosome abnormalities
• dels/dups/inversions/ring chromosomes
• translocations (robertsonian/reciprocal)
• mosaicism
• uniparental disomy (UPD)

Question 2

Name five common chromosomal abnormalities

Answer 2

• Down syndrome (trisomy 21)
• Edward syndrome (trisomy 18)
• patau syndrome (trisomy 13)
• Klinefelter syndrome (47XXY)
• Turner syndrome (45X)

Question 3

Provide some stats for the risk of Down syndrome in relation to maternal age

Answer 3

All ages = 1/650

• 20yrs = 1/1500
• 30yrs = 1/900
• 40yrs = ~1/100

Question 4

What are the two common type of chromosomal translocations and what forms can they take?

Answer 4

• Robertsonian and reciprocal

- balanced/unbalanced forms

Question 5

Describe Robertsonian translocations. In what chromosomes do these occur?

Answer 5

non-reciprocal translocation between two paired/different chromosomes. participating chromosomes break at their centromeres and long arms fuse to form single large chromosome with single centromere. short arms also join to form smaller reciprocal product (usually lost within a few cell divisions)

These occur in the five acrocentric chromosomes (13,14,15,21,22)

Question 6

What is a reciprocal translocation?

Answer 6

Usually an exchange of material between non-homologous (different) chromosomes. Can be balanced or unbalanced

Whilst balanced translocation individuals may be phenotypically normal, they have an increased risk of creating gametes with unbalanced translocations

Question 7

Give examples of sex chromosome abnormalities

Answer 7

• Turner syndrome 45X (can be mosaic: 45X/46XX, 45X/47XXX, 45X/46XY)
• Triple X
• Klinefelters (47XXY)
• XYY syndrome

Question 8

Micro deletion syndromes are usually too small to be picked up by standard karyotyping - how would we pick them up instead?

Answer 8

FISH testing

Question 9

Name some common microdeletion syndromes

Answer 9

1. Angelman/Prader-Willi: 15q11-13
2. Williams (elastin gene): 7q11.23
3. Velocardiofacial/digeorge: 22q11.2
4. Smith-Magenis: 17p11.2

Question 10

6% of unexplained mental retardation can be attributed to what?

Answer 10

Cryptic telomeric translocation

Question 11

What are the indications for a chromosomal analysis?

Answer 11

greater than or equal to 2 of the following:

• Dev delay/LD
• intrauterine growth failure/failure to thrive
• microcephaly
• facial dysmorphism
• multiple congenital malformations

Question 12

What are the recurrence risks for the different types of Down syndrome?

Answer 12

• trisomy 21 (mum under 37) = 1%
• mum 14/21 trans carrier = 10%
• dad 14/21 trans carrier = 2%
• either parent 21/21 trans carrier = 100%