Genetic Epilepsy

Gene: NOTCH3

Green List (high evidence)

Pre-print (https://sciprofiles.com/publication/view/62eb776390415f0166f73fae7cd172ed)

Review of research and diagnostic databases and literature review found 50 individuals from 31 families with biallelic variants.

13 PTCS (including splice) and 15 missense resulting in gain or loss of Cys residue.

AR PTCs are associated with early onset leukoencephalopathy including cognitive decline, dev delay/ID and dysmorphism; seizures, spasticity, hypotonia, ataxia

AR missense are associated with CADASIL-like phenotype

Created: 30 Apr 2024, 5:02 a.m. | Last Modified: 30 Apr 2024, 5:02 a.m.

Panel Version: 0.2611

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
neurodevelopmental disorder MONDO:0700092, NOTCH3-related

Variants in this GENE are reported as part of current diagnostic practice

Red List (low evidence)

CADASIL typically presents with adult-onset migraine, TIA/stroke, cognitive disorders. Seizures noted in 5-10% of patients with CADASIL, usually preceded by stroke. Less than 5 cases described of adult-onset epilepsy as initial presenting symptom of CADASIL. All had characteristic MRI-B changes and review of cases shows that a number of them had preceding migraine or other symptoms.

Not suitable for inclusion in genetic epilepsy panel as seizures are adult-onset, rarely observed, and usually develop as a secondary phenomenon.
Sources: Expert list, Literature

Created: 17 Oct 2021, 11:50 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
?Myofibromatosis, infantile 2 - 615293; Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1 - 125310; Lateral meningocele syndrome - 130720

Publications

• 33020014
• 30776699
• 21414809
• 30056822
• 17675836