GiM: Familial Cancer Syndromes and Dysmorphology

Question 1

What are oncogenes?

Answer 1

Genes that code for proteins that stimulate growth.
Regulate cell growth & differentiation.
Gain of function/ activating mutations increase the risk of cancer.

Question 2

What is Knudson’s 2-hit hypothesis? What is a classic example of this?

Answer 2

The hypothesis that cancer is a result of accumulated mutations to a cell’s DNA.
Retinoblastoma= childhood ocular cancer. Rb1 gene (gatekeeper gene), both genes lost/mutated in tumour. Bilateral cases= germline, but also high new mutation rate.

Question 3

What is Familial Adenomatous Polyposis (FAP)?

Answer 3

Hundreds of bowel polyps (adenomas) from teens onwards.
Accounts for 1% bowel cancers, high risk if untreated.
APC tumour suppressor gene
Autosomal Dominant Inheritance

Question 4

Hereditary Non-Polyposis Colorectal Cancer (HNPCC- Lynch syndrome)?
What are the 4 genes associated with it?

Answer 4

Accounts for 2-3% bowel cancers
60-80% risk bowel cancer from mid-20s onwards
Other cancer risks (stomach/ endometrial/ ovarian)
Mismatch repair genes.
MLH1 (50%), MLH2 (40%), MLH6 (10%), PMS1/2 (rare)

Question 5

What are some criteria for looking at HNPCC?

Answer 5

One member diagnosed with colorectal cancer <50yrs
Two affected generations
Three affected relatives

Polyps removal will improve survival. Strong association between aspirin and prevention of polyps. Hysterectomy recommended to prevent endometrial cancer.

Question 6

BRCA1&2 links with breast cancer?

Answer 6

• BRCA1&2 are involved in DNA repair.
• 10% cases of breast cancer under 40, and 25% of those with strong FH
• High penetrance genes: breast cancer risk 80%
• Some increased risk of other cancers (prostate, melanoma, male breast)

Question 7

What is Li Fraumeni syndrome and gene mutation is it associated with?

Answer 7

• Greatly increased risk of developing other types of cancer (breast, sarcoma, brain, adrenocortical, leukemia). Close to 100% risk over lifetime.
• TP53 mutations (tumour suppressor gene)

Question 8

22q11. 2 deletion syndrome (DiGeorge Syndrome)…

- mnemonic to remember the symptoms?

Answer 8

Autosomal dominant inheritance
Catch-22:
-Cardiac abnormality (truncus arteriosus, tetrology of Fallot)
-Abnormal facial expression
-Thymic aplasia
-Cleft palate
-Hypocalcemia/Hypoparathyroidism

Question 9

What does Achondroplasia cause?

Answer 9

Rhizomelic limb shortening
Short stature
Foramen magnum compression/ hydrocephalus

Question 10

Beckwith-Wiedemann Syndrome and what does is cause?

Answer 10

• Large tongue
• Exomphalos (weakness in abdominal wall where is joins the umbilical cord)
• Hemihypertrophy (one side of body larger)
• Neonatal hypoglycaemia
• Increased risk of Wilms tumour (nephroblastoma)

Question 11

What is Kabuki syndrome?

Answer 11

Congenital heart disease (50%)
Developmental delay and intellectual disability
Hearing impairment
Cleft palate
Persistent fetal finger pads

Question 12

What is Peutz-Jeghers syndrome?

Answer 12

GI polyps= bleeding, obstruction
Malignancies (colorectal, gastric, pancreatic, breast, ovarian)
Children with this often develop small dark-coloured spots around the lips, mouth, eyes and anus.

Question 13

What is Treacher-Collins syndrome?

Answer 13

Affects the development of bones and other tissues in the face
Cleft palate
Hearing impairment

Question 14

Waardenberg syndrome?

Answer 14

Sensorineural hearing impairment
Iris heterochromia
Premature greying
White forelock
Areas of skin hypopigmentation

Question 15

What is William’s syndrome?

Answer 15

7q11 deletion
‘Cocktail party’ speech= well developed form but weak conceptual meaning
Congenital heart disease
Hypercalcaemia