Diagnosis?

Question

My grandson’s gene test yielded the following result:

Heterozygous TG10/TG12 and heterozygous for the 5T variant IVS8:TG12-5T/TG10-7T in the pyrimidine tract.

We were told there is a 90% chance that cystic fibrosis can be ruled out. But what about the meconium plug at birth and then the ileus at three weeks? The little one turned two months yesterday and is now back in the hospital.

Would you advise us to present to a specialized clinic?

His defecation is still difficult, although it has improved a bit after taking Creon®.

Kind regards and many thanks your effort.

Answer

Dear questioner,

First of all: regardless of the gene test, with a clinical presentation of “meconium plug,” your son needs to be seen at a cystic fibrosis clinic.

This can also be derived from the comment that “there is a 90% chance that cystic fibrosis can be ruled out” – this is not very helpful in making a decision, as unfortunately it is possible after all that the rather improbable 10%-case applies.

The gene test result can be interpreted as follows: one of your grandson’s two CFTR copies carries the “T5-TG12” variant, which is thought to possibly cause CF. A European expert group’s statement on this topic literally says: “In exceptional cases, TG12-T5 [....] may cause a mild form of CF” (source: J Cyst Fibros 2011; 10 Suppl 2:S86-S102).

But: cystic fibrosis is a recessive disorder, which means that in order for it to break out, both CFTR copies (the one inherited from the father as well as the one inherited from the mother) need to be defective. Your grandson’s other chromosome, according to the gene test, which says “TG10-T7”, is “completely normal,” i.e. a healthy CFTR gene. Translated, the gene test result means: a hint to cystic fibrosis has only been found on one of your grandson’s two CFTR genes – unfortunately, this does not mean that he is healthy, because a gene test can not rule out cystic fibrosis, since it does not detect all disease-causing variants of the cystic fibrosis gene.

In conclusion: please present to a nearby cystic fibrosis clinic. Unfortunately, a gene test can not rule out cystic fibrosis, since it is not possible to distinguish between “no disease-causing CFTR variant was found” and “a disease-causing variant does not exist” by way of genetic analysis.

Best wishes,
Frauke Stanke

04.11.2013