Genetic testing of a sibling in spite of negative sweat test?

Question

Dear expert team,
we have a daughter at toddler's age suffering from CF as well as a son of 7 years. At the time the diagnosis of CF was made in our daughter, we also had a sweat test done to our son.
This test showed a value of 11 mmol/l in the normal range. The sweat test had been performed at the same children's hospital as the one from our daughter, there are already some CF patients cared for there and I think the test has been done correctly.
Now it is like this that our son has again and again cough for several weeks (more than our daughter with CF). We are right now again in such a phase of cough (productive cough, also wheezing) that already lasts for 5 weeks. Now I think every time, can it be that the sweat test was false negative respectively probably not every CF patient has a positive sweat test. I know e.g. about a CF-patient who had 3 times non-elevated values and only the blood test gave clarity, and that after 20 years.
The pediatrician prescribed montelukast to our son. He takes it now for 13 days and the cough is unchanged (especially in the mornings in bed and in case of exertion, i.e. in case of running or jumping etc....).
The last throat swab of our daughter showed Haemophilus influenzae, however she has not any complaints at all (no cough, no rhinitis...). Is it not possible that our son has also this Haemophilus influenzae and this is causing the cough?
At the last visit at our pediatrician I would actually have wanted a throat swab to be done on my son, this has however not been regarded to be necessary and therefore montelukast has been prescribed. The pediatrician assumed that it was a viral thing and the bronchi still had an inflammation.
Our son is also regularly present at the physiotherapy appointments of our daughter and participates in nearly all excercises. Also there he coughs a lot and the physiotherapist said, this did not sound like viscous mucus, it would be loose.
How do you judge the situation? Does a genetic testing make sense? Does the health insurance covers unproblematically a genetic testing for a sibling even if the sweat test had been negative?
I am looking forward to your anwer. Many thanks.

Answer

Hello,
cough is a frequent symptom for very many different diseases. The negative sweat test excludes a classical CF to the greatest extent. In rare singular cases it is false negative or also false positive. In case in here is uncertainty, the doctor can indicate a genetic investigation and either perform it himself or delegate it to a center with human genetic expertise. After the indication from the physician, the costs are covered of course by the health insurance. with a chloride value of 11 mmol/l the result is not even boderline but in the normal range. Talk about your worries also at the CF center, where your daughter is cared for. Then one can there plan a common approach with the pediatrician. Complaints in case of exertion point more at an exertional asthma and a bronchial hypersensitivity. This suspects also your pediatrician. Therefore, I find the therapeutic attempt with montelukast very good. In case of further remaining cough, one should investigate further. Allergies? Asthma? Reflux of stomach acid?

Yours sincerely,

Dr. Olaf Eickmeier

12.06.2013

12.06.13
It has to be emphazised that it is important that the sweat test has to be performed by an experienced center according to existing guidelines: using the so-called "pilocarpine ionotophoresis" to measure the chloride concentration in the sweat. If this is true for the above mentioned case, the sweat test is indeed in the normal range (if chloride concentrations are under 40 mmol/l, the sweat test is re regarded to be negative) and gives a high porportion of security to exclude CF. If it is not assured that the test has been performed like this, it should be repeated under the above mentioned conditions.
Genetic testing may be of importance in case of doubt, otherwise genetic testing of the sibling to reveal a carrier status of one CF-mutation is important for the later family planning of the child itself, but it should be defered until the child is old enough to understand the issue and requests the test in person.
D. d'Alquen