What causes CADASIL?

CADASIL is caused by the mutation of a single gene named NOTCH3 which is situated on Chromosome 19. A mutation is a permanent change in a piece of our genetic makeup (DNA) that prevents it from doing its original function. This gene is responsible for the proper functioning of the vascular smooth muscle cells (VSMCs) which provide the structural integrity and regulate the desired diameter of the blood vessel. In CADASIL the mutation means that progressive and inadequate blood flow causes the degeneration of the VSMC in the arteries.

VSMC make up the majority of the blood vessel wall and regulate the local blood pressure and volume of blood vessels (by contraction and relaxation) travelling through the blood vessels. In CADASIL both the structural integrity of the blood vessels and their capacity to dilate and contract is affected. Degeneration of VSCMs in CADASIL leads to progressive wall thickening and fibrosis. This causes narrowing of the vessels internal diameter in small and medium sized arteries that penetrate deep into the brain.

In other words, due to CADASIL, the muscle cells in your blood vessels (arteries, veins and capillaries) that regulate how much blood, and thus oxygen your organs get is damaged by the mutation and your organs are not able to work optimally.

Complications

Diabetes, Hypertension and excessive build-up of cholesterol in the blood (Hypercholesterolaemia) need to be carefully monitored as they are all risk factors in CADASIL.

How do you get CADASIL?

CADASIL is an inherited condition caused by mutations in the NOTCH3 gene on Chromosome 19. It is inherited in an autosomal dominant pattern. We have 22 pairs of non-sex chromosomes called autosomes and 1 pair of sex chromosomes; the X and the Y. A woman has 2 X chromosomes whilst a man has 1 X and 1Y Chromosome. CADASIL is an autosomal dominant disorder which means the faulty copy (allele) dominates the good copy producing the disorder.

What happens in every pregnancy if one parent is affected?

  • There is a 50% chance that the child will inherit a faulty copy and a working copy and will get CADASIL.
  • There is a 50% chance that the child will inherit both working copies, will not get CADASIL and cannot pass it on.

What happens in every pregnancy if both parents are affected?

This is a very rare occurrence in an Autosomal Dominant pattern.

  • There is a 25% chance that the child will inherit both working copies, will not get CADASIL and cannot pass it on.
  • There is a 50% chance that the child will inherit a faulty copy and a working copy and will get CADASIL.
  • There is a 25% chance that the child will inherit both faulty copies and usually will be severely affected.

It also can be a new mutation, therefore, it will be the first time and there will be no family history.

Contact ACSN

Please feel free to contact us with any questions or enquiries you have