Cystic fibrosis

Question

I do not know if I am right here, however I am desperate at the moment and do not know what to do next. In my son, 2.5 years old, the mutations Q1035X in the CFTR data base and D1152H in the CFTR as well as in the CFTR 2 data base have been detected (after 4 negative sweat tests). What does this mean for us, will our child be severly ill or is that a mild form? What do we have to envisage, feel a bit left alone by the physicians. What about a further child, should we better leave it, respectively what about the case if I am already pregnant? I am sorry that I bother you with such questions, but I just do not know what to do next.

Answer

Dear questioner,

at first in advance: the combination of both CFTR-variants determines the severity of the illness of cystic fibrosis, concerning your son I will answer first of all in three parts:

1. What does D1152H mean for your son?
2. What does Q1035X mean for your son?
3. What can be derived from the combination of D1152H and Q1053X?
And I will then answer the question about a new pregnancy. In this case, I assume that in your son both CFTR-variants D1152H and Q1053X have been found on two different chromosomes (that reads: you have e.g. inherited D1152H, your husband Q1035X or vice versa). "CFTR 2" is an internet database, there can only be found information about D1152H - Q1053X is so rare, that there is no information about it in the "CFTR 2".

1. What does D1152H mean for your son?
D1152H is a CFTR-variant, that is accompanied by a so-called variable phenotype: in some patients with mild CF D1152H has been found - mild CF means: the pancreas is functioning, the organs involved in CF are mildly involved. Furthermore, D1152H has also been found in some patients with a so-called CFTR-related disease - these patients do not show the typical whole body disease of CF, but only a part of the symptoms (e.g. only complaints of the lung, no complaints of the digestional tract).
This means in translation: some people with D1152H have CF, some people with D1152H do not have CF. The experts are therefore not sure, how D1152H has to be classified - therefore for sure the insecurity of a clear convention of speech concerning the diagnosis, that you experience at the moment.

2. What does Q1053X mean for your son?
There is one description of the course of the illness of Q1053X: in the year 2004 the collegues Nadja Bogdanova, Bernd Dworniczak and Jurgen Horst from the institue of human genetics of the university of Münster [Germany] described a 29-year-old CF patient, who carries on one chromosome Q1053X. The authors described the course of the illness as mild.

3. What can be derived from the combination of D1152H and Q1053X?
Your son will not suffer from a severe CF, as D1152H as well as Q1053X are described either with mild CF (for D1152H and Q1053X) or are only associated with manifestation of a CFTR-related disease (described for D1152H). This you do already know: the sweat test has been negative several times, that means the salt channel CFTR functions well enough in your son. In spite of this it is important that you make use of the actual progess of medicine for your son: look for a specialized CF-physician at a specialized CF-center [adresses were provided for the German CF-centers via the website of the German patient organization]. Regular check-ups will show, which (or if necessary at all) drugs and therapies are necessary. In any case it pertains: even people with restricted CFTR-dysfunction, in whom the diganosis CF is not made in the end, profit from the experience of a CF-physician in dealing with symptoms like e.g. recurrent colds in childhood. A precise prediction of the furhter course is not possible with D1152H/Q1053X: environmental factors (like e.g. the treating physician, access to specialized drugs) have great influence on the symptoms.

Now to your question about a further pregnancy: please ask a specialist for human genetics, you are in a typical counselling situation. D1152H and Q1053X can be detected genetically.
However: only if the child has inherited both variants, the question "CF or not" can occurr. Somebody, who carries only D1152H is as healthy as you (or as healthy as your husband), somebody who carries only Q1053X is as healty as your husband (or as you). Only the combination of both CFTR-variants can lead to clinically detectable CFTR-dysfunction in the child, the parents are both healthy and carry one of both variants each. The chance that a future child inherits both variants from the parents is 1/4.

With best wishes for your son,
Frauke Stanke

09.09.2013