Cystic fibrosis help - interpreting results

[CFhelp]

Hi,

My partner was diagnosed with CF last week - I have no idea where to post this but is there anyone with any knowledge out there that could help decipher what this all means please?

We only found this out via fertility investigations so it came as a massive shock, we just don't know what this means or what's next..

The fertility consultant acknowledged he knew nothing about CF and said we would need to wait to be referred to genetic specialists but that there will be a really long wait so in the meantime, we are left just knowing what's on the attached. My partner is becoming increasingly anxious (as am I and it's difficult to support him when we need answers to lots of questions).

Any help deciphering the attached or signposts to any good websites/info sources would be most appreciated!

Thanks so much.

I don't know much at all on this subject but do know people who have been investigated to see if they had the gene, in turn the risk of their child having CF. I don't think carrying the gene means he has CF? CF is a lifelong condition that he would have needed medical attention for from childhood. I think that both parents need to be a carrier of the same gene, for the risk to be passed on to the child. Sometimes both parents can carry the gene and go on to have a child without CF.

Hopefully someone more knowledgeable will come along with some answers.

From what I know men with CF tend to be infertile. There is also the issue around passing along the gene. Now if he's a carrier which is likely if he's only just been diagnosed that could be a very different picture.

Thank you for your response.

I know we thought the same, but he was told he actually has it but it is mild and rare, so would still be a risk in terms of offspring in terms of passing on CF. We just don't understand the results (only just picked them up from the hospital today). We don't think he has absence of the vas deferens as he does have sperm, albeit a low count. So many questions!

I know I need to be tested once referred to genetics and then we will need to decide based on that the next steps with IVF/potential testing etc.

It's just the wait now for the referral, it's been one thing after another. Just trying to look up info re these mutations in the meantime.

Thanks again.

If he had the disease he’d have been diagnosed and treated as a child, CF is a significant disease I don’t think you can get to adulthood and not know you have it.

Sounds like he is a carrier of CF. Therefore your children could be affected if you’re also a carrier and inherit those genes from both of you.

As it says in the letter you as his partner can get screened to see if you’re also a carrier. If not your children won’t have CF but they may become carriers themselves- it says in the letter they can be screened for this when born so they know.

You need to get screened I don’t think it’d be expensive.
What was the context of the test? Are you having fertility investigations? Just trying to understand context.

Thank you.

Yes we've found that on research, but he's had multiple semen analysis over the last year and an ultrasound of his testes etc and although low count (which is why we started all of the fertility investigations over a year ago in the first place), he does have sperm present (between 1-4 million total motile sperm and a normal volume) - so none of it seems to add up!

He has no other symptoms of CF although has had mild asthma since he was a child, but runs marathons and exercises regularly so nothing of concern.

So many questions, we will probably need to wait to be referred to genetics it's just the wait isn't it!

Thanks for responding.

Read this, sounds mild. I don’t think it’s a mutation that represents serious disease. Did you not have a follow up with a genetic counselor though so you can understand it better.

www.sciencedirect.com/science/article/pii/S156919931100049X

Thank you, yes all very strange (see my other responses). We was told he does have it, but it's mild and rare and in fact, he was told "he is very lucky as it could have been a lot worse", but also, it was the fertility consultant who told us this and also said he knows nothing about CF... the letter reads as though he has it, but it could be asymptomatic (but I have no idea re the letter contents in all honesty!!).

Yes, this has only come about via fertility investigations . His karotype tests came back as normal, but he's got low sperm count etc.

Thanks for responding

I did a genetics degree a looong time ago. I'd read those results as:

He has one copy of a 'pathogenic' CF allele. This means he carries CF - his children have a 50% chance of inheriting this, those who do would also be carriers. If you don't carry CF they can't inherit two copies and be affected.

He also has a CF-related allele, which is associated with abnormal sperm. He has two copies of this. Any children would inherit one copy from him. Again, if you don't carry this, they would also have a 'normal' copy from you.

It's possible that he does have another rare 'pathogenic' CF allele that was not tested for. They can do further tests to determine this.

Has he actually been diagnosed with CF? Does he have symptoms?

Thanks so much. Will take a look.

No, this was fed back by the fertility consultant who didn't know a thing about CF and said we would need to wait for referral to genetics to know more and discuss, but implied we would be waiting months and months when asked... so just trying to do some research.

Thanks again

CF is usually detected shortly after birth. I've never heard of anyone being diagnosed with it as an adult. I know someone with the condition and they are monitored annually but they also sometimes get ill enough to be hospitalised. It's a teenager that I know.

Im sure both parents have to be carriers. Neither of the parents I know have CF.

Sorry, I took so long to type there were loads of x posts.

Even if he has two 'pathogenic' CF alleles (one being mild and undetected by this test), assuming you don't have any, children will not have CF, but will be carriers.

I think it means your husband carries the gene that causes CF, if you carry the same gene any child you have will have CF, if you do not carry the gene you still may have a child with CF. Men with CF gene may be able to have children otherwise there wouldn’t be any people born with it. You can carry the gene but not be ill. Is there anyone in your husbands family with CF? Im surprised this hasn’t been picked up before tbh. Hope this helps. Having worked in paeds and having a child that thankfully tested negative for this, I wouldn’t wish this disease on anyone, but treatments have improved in 30 years

So you think it reads as though he is a carrier, rather than having it?

We were told he actually has it (although mild and rare) - very confusing!

Thank you.

Thanks so much. Doing research, it appears loads of people are carriers without realising, so after being told he has it (and isn't just a carrier), we assumed his parents must have been carriers (his Dad is no longer with us) without knowing.

It's all been a bit of a shock, probably not helped as the initial conversation was with the fertility consultant who didn't know anything! x

That is not an easy report to read is it for a lay person! He has one copy of one of the classic (Caucasian) mutations, but he also has two copies of a ‘milder’ mutation. So he might have a milder version of CF but variable presentations have been reported. Or he might have no symptoms at all.

A clinical geneticist or genetics counsellor should be able to talk this all through, in terms of what this means for your partner and any future children. They might want to do testing like sequencing the gene as opposed to just testing for specific mutations. They can also organise testing for you and also your partners family. I hope you don’t have to wait too long for an appointment.

Thank you.

That's what we have been working on the basis of.. Based on my tests, if I am a carrier, then we would do testing via IVF (knowing the child would be a carrier, but not actually have CF), but if I'm not; then it would make no difference; any child would be a carrier but not have CF, but we would likely still need IVF due to low sperm count etc.

Sorry if my posts are unclear, my brain is scrambled! x

Yes. I think because he has two copies of the CF-linked allele it's more likely he has another pathogenic CF allele that hasn't been detected, but more likely doesn't mean likely, if you see what I mean.

Given he is asymptomatic I'd probably put my money on his being a carrier rather than having two different CF alleles, one very rare, causing very mild almost undetectable CF.

Again, CF requires two copies of a CF allele, so if you are clear children will not be effected, even if he has two copies.

On this response and the link I sent you sounds like he is a carrier for serious disease but also he has another cf mutation type that is mild and doesn’t impact lungs or intestines but does impact his fertility.
No doubt for ivf etc they want you to get tested too to assess the risk of any children having the serious disease and maybe offer you screening to transplant embryos without it if you are a carrier too.

All the best to you both. Sounds like he is in good health otherwise.

That's what we thought, but some forms of CF are mild apparently that can be asymptomatic.

It's all just come as a shock and so unclear but hopefully we can get some answers so we can move forward!

Thanks for responding

It's mind boggling isn't it and don't think we will understand much more until we can speak to the genetics specialists - it's just waiting with this letter and knowing very little more is frustrating. I feel for my partner so much who feels really anxious!

Thanks for responding, fingers crossed for a speedy referral.

Give the CF Trust a ring. They should be able to help understand about any v mild/rare versions.

Cystic Fibrosis Trust

Thank you, tried to give them a call earlier but no answer. Will try again tomorrow!

im sorry I don’t understand the report so can’t really help other than to say I’m sorry you’ve been left hanging in the dark like this. I have a family member with a comparatively mild variant that was diagnosed as a teenager. They are on drugs that help a lot, although do get ill quite a lot (but generally have normal life - exercise, full time job etc). They have biological children (following genetic testing that showed their partner was not a carrier). The CF trust are a great charity and brilliant advocates for patient needs/ new treatments.

We were tested when we had IVF because my husband's brother had CF. Which means that his parents must both carry a gene for CF. Because my husband doesn't have it, it meant that we knew he either carried one gene from one of his parents or that he want a carrier.

In the general population, 1 in 25 people carry one gene.
If both parents carry the gene and have a child then there is a 1 in 4 chance of the baby having CF, a 2 in 4 chance of the baby being a carrier and a 1 in 4 chance of them not being a carrier.

My GP was absolutely useless (quoted that only 1 in 250 in the general population were carriers so why were we worried), but once we were referred to the genetics team, they were fantastic. I ended up ringing the department at Liverpool to find out how to get a referral another way because the GP was so useless. The CF Trust website is fantastic for info- it's where I got the phone number for the hospital department from.

Both my husband and I were tested. He's a carrier and I'm not, so no chance of our children having CF (but we will get them tested at some point to see if they are carriers just so they know for when/ if they decide to have children).

The specialist who we saw to get our results from was fantastic at explaining everything - including that the blood test doesn't test for every single type of CF gene - some very very rare ones aren't tested for.

I think the main things to focus on are trying to push for a test yourself (ours were both done on NHS about 4 years ago, but you could look at going private if it's not likely you'll get one any time soon) and getting an appointment for someone to explain this 'mild CF-like gene.

I do recall a case a few years ago where a guy found out that he had some form of CF because he was diagnosed as infertile from it. He never had CF symptoms, but it was in the news because he'd believed the two children he'd raised and then paid child maintance for were his, only to find out later in life that he was actually infertile and couldn't possibly be the father. Sounds quite similar to what your DP may have.

My son, now 21, is a CF carrier (5T11TG) and is symptomatic. He was seen at Brompton hospital , London when he was 16 as he has intermediate sweat test results. The consultant said he could not rule out full CF as he may have rare mutation that has not been detected yet. He said if he wanted children when he was older they would test to see if he has CBAVD.