CADASIL [the NOTCH3 gene] [1 gene]
Cerebrovascular diseases represent a reasonable percentage of neurological consultations in adults, and genetic factors can be among the underlying etiological causes. On top of different risk factors of this nature, a series of diseases following a Mendelian pattern of inheritance have been described. Although their prevalence is low, establishing a diagnosis allows for a more specific clinical management and family counseling.
Among the conditions considered for the development of these panels is particularly relevant cerebral microangiopathy, in which we highlight the following phenotypes:
- CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, the NOTCH3 gene). CADASIL is a disease characterized by episodes of recurrent ischemic stroke that begin in adulthood and are associated with cognitive decline that leads to dementia, migraine with aura, psychiatric disorders, and diffuse white matter lesions and subcortical infarcts on neuroimaging, with typical involvement of anterior temporal lobes.
- CARASIL (cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy, the HTRA1 gene). CARASIL is characterized by deep white matter alterations of early onset. Affected individuals may present with gait abnormalities due to spasticity, stroke-like episodes, mood disturbances, pseudobulbar palsy, and cognitive decline beginning between the ages of 20 and 50.
We have also developed a specific panel for familial cavernomatosis and other monogenic diseases, such as familial hemiplegic migraine, and diseases that present an imaging pattern in cerebral angiography similar to Moyamoya disease.
Priority Genes : Genes where there is sufficient evidence (clinical and functional) to consider them associated with the disease; they are included in the clinical practice guidelines.
Secondary Genes: Genes related to the disease, but with a lower level of evidence or that constitute sporadic cases.
* Candidate Genes: Not enough evidence in humans, but potentially associated with the disease.
- Ilinca A, Samuelsson S, Piccinelli P, et al. A stroke gene panel for whole-exome sequencing. Eur J Hum Genet. 2019 Feb;27(2):317-324. doi: 10.1038/s41431-018-0274-4.
- Mancuso M, Arnold M, Bersano A, et al. Monogenic cerebral small-vessel diseases: diagnosis and therapy. Consensus recommendations of the European Academy of Neurology. Eur J Neurol. 2020 Mar 20. doi: 10.1111/ene.14183.