CYSTIC FIBROSIS Flashcards
Scenario 1.
A woman is 8 weeks pregnant and known to be a carrier of cystic fibrosis.
Her husband is Caucasian.
What is the risk of the child having cystic fibrosis?
Answer. 1 in 100. The risk of both being carriers is 1 in 1 for her multiplied by 1 in 25 for him. This gives 1 in 25. There is then a 1 in 4 risk of the child being affected, so the answer is 1 in 100.
Known carrier, mom: 1/1
Husband caucacian: 1/25
Both Carrier sum: 1/1X 1/25 = 1/25
Diseased: 1/4 X 1/25 = 1/100
About 1 in 25 Caucasians is a carrier. It is believed that carrier status is less prevalent in Afro-Caribbeans and Asians, but we don’t know exact figures. We should soon have a better idea of the figures for UK Afro-Caribbeans and Asians since the introduction of universal neonatal screening.
If both partners are carriers, there is a 1 in 4 chance of an affected child.
Make sure you can do the simple diagram of all the possibilities so that you can work it out if you forget in the heat of the exam.
The mother’s genes are: CF and N. CF = a cystic fibrosis gene, N = normal.
The father’s genes are: CF and N.
As I am baby-minding a granddaughter as I type, I have made it pink for girls and blue for boys!
The mother’s CF gene can link with either of the father’s genes.
CF + CF → the child will be homozygous for CF and have cystic fibrosis
CF + N → the child will be heterozygous and a carrier of CF
And her normal gene can do the same.
N + CF → the child will be heterozygous and a carrier of CF
N + N → the child will have no CF genes and will be “normal”.
This simple list of the permutations gives us the 4 possible outcomes in autosomal recessive inheritance:
1 chance in 4 of having the disease.
1 chance in 4 of being “normal”.
2 chances in 4 of being a carrier.
But this is not the case if one partner has CF. A man with CF will be almost always be sterile and we can assume he is sterile for the purposes of the exam.
A woman with CF must hand on a CF gene to all of her children. If her partner is a carrier, half the children will get a CF gene from him too and will have CF. The other half will get his normal gene and be carriers. If he is not a carrier, all the children will be carriers
Scenario 2.
Healthy woman attends for pre-pregnancy counselling.
Her brother has cystic fibrosis. Her husband is Caucasian.
He has been screened for cystic fibrosis. The test was negative.
What is the approximate risk of them having a child with cystic fibrosis?
MOM carrier: 2/3 (1 sibling affected)
Husband caucacian: 1/250 ( after test negative)
Both Carrier sum: 2/3 X 1/250 = 2/750
Diseased: 1/4 X 2/750 = 1/1000
Answer. About 1 in 1,500.
Her risk of being a carrier is 2 in 3.
His risk of being a carrier was 1 in 25 before testing.
And about 1 in 250 after testing, assuming testing to be about 90% effective.
The chance of both being carriers is 2/3 x 1/250.
The chance of an affected child is 1/4 x 2/3 x 1/250.
This is 2/3 x 1/1000.
Which is 1/ 1,500.
Explanation. Her brother is affected. Therefore, both parents must be carriers. Unless you are told otherwise you ignore the rare possibility that one parent has CF.
She was born with 4 possibilities: 1 of being “normal”, 2 of being a carrier and 1 of being affected.
She is healthy, so is not affected. This only leaves 3 possibilities, 2 of which are being a carrier, so her risk of being a carrier is 2 in 3.
He is Caucasian, so his starting risk is 1 in 25, the average for Caucasians.
If we assume that screening is ~ 90% effective, his risk after a negative screen becomes 10% of this starting risk. This takes his risk to 1 in 250.
The chance that they are both carriers is her risk multiplied by his risk. This is 2/3 multiplied by 1 in 250. The risk of an affected child is then ¼ of this.
Scenario 3.
A healthy woman is a known carrier of cystic fibrosis.
She attends for pre-pregnancy counselling. Her husband has cystic fibrosis.
What is the risk of them having a child with CF?
Answer. This is the trick question you need to look out for. He will be sterile, so there is no point in tests. There is a tiny chance that he is not sterile and the possibility of pregnancy via retrieval of spermatids from the testes and then ICSI and IVF. But don’t get screwed up by the tiny chance that he is fertile; for the exam we assume him to be sterile.
Scenario 4.
A healthy woman attends for pre-pregnancy counselling. Her sister has had a child with cystic fibrosis.
What is her risk of being a carrier?
Answer. 1 in 2. One parent must be a carrier. This gives a 50:50 chance of them handing on the CF mutation to our patient.
Again, you must keep it simple. You can dream up scenarios with both parents being carriers, one being affected etc. But these are very unlikely and we stick with the simplest one, which is one parent a carrier, the other normal.
Scenario 5.
A woman attends for pre-pregnancy counselling. Her mother has cystic fibrosis.
What is the risk that she is a carrier?
Answer. 100%
Scenario 6 .
A woman attends for pre-pregnancy counselling. Her mother has cystic fibrosis.
The partner’s risk of being a carrier is 1 in X.
What is the risk that she will have a child with CF?
Answer. 1 in 4X. She must be a ca
Allchildren will be carriers. If the partner does notcarry any of the common gene mutations for cysticfibrosis, the risk of having an affected child is⬍1:250. If the partner does carry one of thesegenes, the risk is 1:2
Allchildren will be carriers. If the partner does notcarry any of the common gene mutations for cysticfibrosis, the risk of having an affected child is⬍1:250. If the partner does carry one of thesegenes, the risk is 1:2
antenataldiagnosis can be performed by chorionic villusbiopsy in the first trimester. Alternatively, in vitrofertilisation with preimplantation genetic diagnosis
antenataldiagnosis can be performed by chorionic villusbiopsy in the first trimester. Alternatively, in vitrofertilisation with preimplantation genetic diagnosis
