The Genetics of PXE

PXE is always a genetic disease. That is, it is always caused by a combination, or combinations of altered genes, ie genes that are not normal - also called "mutant" (changed) genes. That is why PXE is always referred to as a genetic disease. Unfortunately, the fact that it is classed as a genetic disease does not mean that we can identify the pattern of inheritance in every single family in which it occurs.

Every human being has to sets of genes, one set of which is inherited from the mother, in the ovum or egg and one set which is inherited from the father, in the sperm. Every human being therefore has two copies of every gene except those that determine gender (sex). There is no form of PXE that is X-linked or sex linked.

Recessive Inheritance

PXE is recessive. In this situation, each parent is a carrier for one mutant copy of a different PXE gene, which, when coupled with a normal copy is undetectable. That is, it causes no recognisable diseases or trait. So, when two carriers have children there are four possible outcomes to any pregnancy:

  1. The child gets one normal copy from the male side and one normal copy from the female side. Thus, this is entirely genetically normal and appears normal.
  2. The child gets the normal copy from the male side and the PXE copy from the female side and is therefore a carrier same as the parent but has no detectable trait.
  3. The child gets the PXE copy from the male side and the normal copy from the female side and is therefore a carrier same as the parent but has no detectable trait.
  4. The child gets the PXE copy from the male side AND the PXE copy from the female side, The child thus has two PXE copies and NO NORMAL COPY. This child is therefore affected.

There is no way of proving that the parents are carriers until they have another affected child, in which case, the only reasonable interpretation is that both parents are carriers. The risk to any subsequent pregnancy is one chance out of four to be affected and three chances out of four that the child will not have the trait and will appear normal. (But remember, two of those three normal-appearing children will be carriers, and one of the three will be genetically normal-normal).