Definition, Transmission, Frequency

Disease Definition

CADASIL:  (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy).
 
This very descriptive name was proposed in 1993 by two researchers, Professors Bousser and Tournier-Lasserve who have helped identify the disease thanks to advances of MRI Technology and Genetics. It means that the disease affects arteries in the brain; it is autosomal dominant i.e. it can be passed or inherited through one of the parents; and it results in subcortical infarcts and leukoencephalopathy (brain white matter diseases).

The disorders are caused by cerebrovascular strokes (myocardial infarction of small arteries).

The disease is linked to impairment of muscle cells surrounding the blood vessels (vascular smooth muscle cells) responsible for contraction of the arterial walls, which are abnormally thickened. This arterial disease affects all organs, however it results only in neurological signs caused by poor blood flow in some areas of the brain.

A mutation of the NOTCH3 gene on chromosome 19 is responsible for the disease.
 
Neurological disorders affect motor, sensory and/or psychic brain functions.

Meaning of Acronym:

• Cerebral: related to the brain.

• Autosomal Dominant: describes the genetic nature of the disease and its mode of transmission.

• Arteriopathy: generic term describing all diseases of the arteries.

• Subcortical: pertaining to the central region of the brain, consisting mainly of the white matter.

• Infarcts: brain damage, due to partial or total interruption of blood flow (infarction, also called strokes) located in the white matter of the brain.

• Leukoencephalopathy: "leuko" means white in Greek, "encephalo" refers to the brain and "pathy" disease, hence a disease of the brain’s white matter.

This name summarizes the main characteristics of the disease. For the sake of international understanding, the term was determined in English although the disease was discovered and described by a French medical team.

Disease transmission

CADASIL is a genetic disease with a transmission mode called "autosomal dominant", meaning it touches both men and women and on average one out of two children born to an affected parent. The disease is caused by an abnormality of the "NOTCH3" gene located on chromosome 19.

Each child of a parent with CADASIL has a 50% risk of carrying the disease.

Disease frequency

The exact frequency of CADASIL has not yet been determined. It is still widely underestimated. Hundreds of families have been identified worldwide. The disease affects both men and women and on average, one out of two children born to an affected parent is at risk of inheriting this disease.

In France, about 300 patients in 2014 were monitored at the Lariboisière Hospital. Taking into account the number of undiagnosed individuals due to misdiagnosis or young gene carriers having not yet exhibited symptoms, we can assume that the number of people carrying the CADASIL gene is much higher.

Sporadic cases have been identified where a person has undergone genetic mutation while his/her parents are not carriers ("de novo" mutation).

For more information, refer to CERVCO web site. (in french)♦