02.01.2005

In the moment when a women's egg is fertilized by a man's sperm, the baby's gender is determined:
If two X chromosomes come together, the baby becomes a girl; if one X and one Y chromosome come together a boy is developing.

If you imagine a boy inheriting only a "defect X" (and not a second and dominating X) plus his gender determining Y chromosome you can understand that he will be born with the disease, whereas a girl whose "healthy X" dominates the "defect X" will usually not express the disease.

There are rare exceptions; according to some researchers this is due to a certain process called X inactivation (and if the "healthy X" is inactivated, the "defect" gene can make females express the disease - but normally not fully!). But the vast majority of the afflicted individuals is male!

Females, however, who carry one "defect X" (even without expressing any symptoms) can pass the disease on to 50% of their sons, and 50% of their daughters normally become carriers. This is the statistics. But some families seem to have different medical histories. Genetic counsellors will try to answer the specific questions in case a baby is planned.

It must be noted that no woman should feel guilty for having passed a disease gene on to her child. The reason why less diseases are passed on by the Y chromosome is that ther is only a single Y chromosome in males (only) and therefore diseases located on this chromosome are logically not passed on as often as if there were two Y chromosomes. And a woman is indeed not guilty for having two copies of the same chromosomes and for the fact that therefore a disease can be passed on more often.
 
 

Not in every afflicted person is the disease due to the same mutation. Although it is always the gene for the L1CAM proteine(location Xq28, that is the X chromosome, long arm of the chromosome (q), band 28) that causes the MASA (CRASH) syndrome, i. e. the gene responsible for the growth of the neuronal cells during embryonic/fetal development, but there can be either a small or a larger mutation. Thus there may be differences in larger or smaller parts of the genetic program.

In the case of our son Andy there is a point mutation, i. e. of the four possible bases that encode the construction of amino acids only one was changed.

But how can such a small mutation cause such a lot of damage?

Well, indeed there are such small mutations all the time which in most cases do not have a negative effect - that is how evolution works. But in Andy´s case there is a mutation leading to a structural change in the L1CAM proteine that had a negative effect on the proteine's functions. And in this case the result is that the cell adhesion during the development of the brain does not work properly. Thus it comes to problems in the growth of the brain leading to cerebral damages with different symptoms.

Additional info: Andy's doctor in the children's centre of the hospital of the University of Essen let us know that a possible connection between a maternal hypothyreosis (during pregnancy) and the MASA Sydrome is being discussed. It is interesting that this is something I told Andy's genatic councellor in the children's centre in Munich years ago. Now I certainly ask myself whether the initial idea was mine and is now spreading or if others had the same idea. First of all I would love to get to know the final result of this discussion. I myself am suffering from a hypothyreosis that was diagnosed shortly after Andy's birth and should have been worst during pregnancy. Since than I keep wondering whether this fact acted as a trigger (trigger function). In this context it should be stated that only one of our five son's is affected by MASA (and not half of the males).