Hot Topic - Breakage syndromes

Question 1

Describe the testing procedure for Nijmegan breakage syndrome

Answer 1

Irradiate cultures
Score breakage compared to a normal control in 80-100 metaphases.

If abnormal, send for NBN mutation analysis

Question 2

Describe the testing procedure for Ataxia Telangiectiasia

Answer 2

Irradiate cultures
Score breakage/abberations in 50 cells
Check for rearrangements involving the TCR (between chromosomes 7 and 14)

If abnormal, send for ATM mutation analysis

Question 3

Describe the testing procedure for Fanconi Anaemia

Answer 3

Treat with MMC or DEB (clastogens)
Score the number of SCE compared to normal control in 80-100 cells

If abnormal send for Fanconi panel testing. (FANCA, FANCC and FANCG account for 90% of mutations)

Question 4

Describe the testing procedure for Bloom syndrome

Answer 4

Treat with BrDU
Score 20 cells for increased numbers of SCE (often 10x number in normal cells)
May also see quadriradials

If abnormal send for BLM testing

Question 5

Describe the clinical features associated with Fanconi Anaemia

Answer 5

Hypoplastic thumbs
Aplastic anaemia
Microcephaly
Pancytopaenia
cafe-au-lait patches
renal anomalies
Short
Increased risk of AML

Question 6

Describe the clinical features associated with Bloom syndrome

Answer 6

Butterfly rash
Short
Intellectual disability (in some)
long facies
micrognathia
At risk of multiple cancers
UV-sensitive

Question 7

Describe the clinical features associated with Ataxia Telangiectasia

Answer 7

Ataxia
Telangiectasia
Leukaemia
Lymphoma
Radiation sensitive
Breast cancer

Question 8

Describe the clinical features associated with Nijmegan breakage syndrome

Answer 8

Short stature
Microcephaly
ID
Distinctive facies
NHL