GENETICS Flashcards
Mr Davies has a number of relatives who developed hypertension in their 50’s and 60’s.
State the likely inheritance pattern of hypertension in his family (½)
Multifactorial/ complex
Mr Arend lost his father following a heart attack at the age of 42, his paternal grandfather died following episodes of severe chest pain at the age of 39 and both of Mr Arend’s two brothers have been treated for high cholesterol and angina for many years. Mr Arend has a daughter of 30 years.
Draw the pedigree (5)
If this were due to an abnormality in a cholesterol metabolism gene state the likely mode of inheritance (½)
Autosomal dominant
State the risk for Mr Arend’s daughter of having cholesterol problems (½)
50% (1 in 2)
Indicate the term used to explain the observation that the same genetic mutation does not always produce the same severity of illness (½)
Variable expression
State the most common mode of inheritance of stroke (½)
Multifactorial inheritance
Patient is worried as both her mother and her maternal grandmother died after developing a pulmonary embolus following surgery and her mother’s sister had a clot in her leg twice during her pregnan cies. The intern does some genetic testing which shows she has factor V Leiden.
Draw the pedigree (4)
Outline the immediate implications for Ms Smith (2)
Increased risk for deep vein thrombosis - other factors may influence that risk too – would have to weigh up risk and benefits of anticoagulation with surgery but at least take maximum non-invasive precautions against DVT.
Outline two (2) aspects of lifestyle advice you should give her on discharge (2)
Advice against smoking
Certain oral contraceptives should be avoided if possible
Avoiding long periods of reduced mobility
She is concerned about her 7 month old baby girl and 2 year old son. Indicate the risk to each of them of having Factor V Leiden and justify your answer (1) Outline the advice that you would give her regarding having her children tested (2)
Autosomal dominant so each at 50% risk
Reduced penetrance and not expected to alter any care in childhood so generally not recommend in childhood unless particular high-risk situation that will change management
List three (3) genetic disorders that would increase the risk of intracranial haemorrhage and state the inheritance pattern of each: (4½)
- Haemophilia A: X linked recessive
- Haemophilia B: X linked recessive
- Von Willebrands Disease (most autosomal dominant a few autosomal recessive)
- Others… most autosomal recessive.
Mr Botha, a 65-year old farmer was found by his wife, as she returned home from shopping, slumped in a chair. He did not answer any of her questions and appeared to have a facial droop on the right. His wife relates that about a week prior to this, he told her of transient right-hand weakness with difficulty lifting a cup of coffee.
On examination, he was mute, yet able to follow simple commands. He appeared frustrated while trying to answer questions. He had a drooping right side of the mouth and face but had normal movement of the forehead. He had slightly decreased power in the right arm with a right arm drift (i.e. when asked to close his eyes and hold his arms straight in front of him, his right arm slowly drifted out of position.)
Mrs Botha tells you that her husband’s mother died at the age of 28 from a blood clot to her lungs during her 4th pregnancy. He lost his sister, who was a heavy smoker, from a stroke at the age of 48, and his brother had a deep vein thrombosis after flying overseas 10 years ago, but is now well. Mr and Mrs Botha have 2 sons.
Explain how knowing this family history would influence your management of Mr Botha (2)
Draw a genogram of Mr Botha’s family (2)
- Looking for genetic predispositions to thrombosis.
- Avoidance of risk factors.
- Counselling other family members about risk
If there is a genetic disorder in this family, state the likely inheritance pattern (1)
Autosomal dominant
Autosomal Dominant Hypercholesterolaemia is very common in South Africa.
The pedigree for Martha and Jack’s families is shown below (only Martha is known to be affected, the status of all other members of the family is unknown). Martha carries a mutation in the LDLR (low density lipoprotein receptor) gene that predisposes to Familial Hypercholesterolaemia (FH).
For each of the persons labelled 1, 2, 3 & 4 in the pedigree, state whether you would request genetic testing or not. Give one reason for your decision about each person [4]
- Individual 1: [1] is related to Jack and NOT Martha, therefore their risk of carrying a LDLR mutation is at the general population level. I would therefore NOT send them for genetic testing.
- Individual 2: [1] is Martha’s sibling and therefore is at 50% risk of carrying the same LDLR mutation. I WOULD send them for genetic testing.
- Individual 3: [1] Martha and Jack’s children and are all at 50% risk of getting the mutated chromosome from Martha. They too MUST be tested
- Individual 4: [1] As for individual 3
Mitchel’s son, Bob, visits the hospital and tells you that he has haemophilia A for which he gets regular factor VIII replacement. Bob’s only sister, Sally, has a son (Bob’s nephew), with haemophilia. Bob is worried that haemophilia may have caused Mitchell’s brain bleed. Bob is particularly worried as he has a healthy daughter who is married to a man who has haemophilia A and they are expecting twins, a boy and a girl in 2 months.
Draw the pedigree (5)
½ symbols correct; ½ relationship lines correct; ½ each for Bob, his nephew and his son in law indicated as affected; ½ each for his mother, sister & daughter indicated as obligate carriers and ½ if correct symbol for X- linked carrier used.
Do you think that Mitchel (Bob’s father) has haemophilia A? Explain your answer (2)
No. X linked disorder & he got Y from his father and it would be very unlikely for his father to have had inherited it form his mother and only present at this stage of life.
What is the chance of Bob’s grandchildren (expected twins) having haemophilia A? Explain your answer (2)
Boy - 50% chance – their mother an obligate carrier
Girl 50% chance of being affected and 50% chance of being just a carrier – must inherit a mutated X from her father and 50% chance from mother - if mutated x form mom will have haemophilia B, if not will be a carrier.
