# A Very Rare Variant of Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leucoencephalopathy (CADASIL) on the gnomAD Database With Variable Phenotypic Expression

## TL;DR

This paper describes a rare case of CADASIL, a genetic disorder causing stroke and dementia, with variable symptoms and a confirmed NOTCH3 gene mutation.

## Contribution

The paper presents a rare variant of CADASIL with variable phenotypic expression confirmed via genetic testing.

## Key findings

- A 46-year-old man showed CADASIL symptoms including slurred speech and white matter abnormalities.
- Genetic testing confirmed a NOTCH3 mutation as the cause of the patient's condition.
- The case highlights the variable expression and diagnostic challenges of CADASIL.

## Abstract

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is an important genetic cause of stroke and vascular dementia, which may also demonstrate variable phenotypic expression. The causative mutation is in the NOTCH3 gene, which maps to chromosome 19 and is largely expressed in the vascular smooth muscle cells of small cerebral blood vessels. The predominant clinical manifestations of this disease include migraines, subcortical ischaemic events, mood disturbances, apathy, and cognitive decline. We herein describe a 46-year-old man who presented to the emergency department with slurred speech, right-sided facial drop, and right lower limb incoordination. Three years before the presentation, he had episodes of right-sided leg stiffness and visual disturbances, which were suspected to be a demyelinating event. Physical examination confirmed increased tone in his lower limbs, worse on the right. His brain MRI showed severe, widespread white matter T2 signal abnormality. The possibility of an adult-onset leucodystrophy was entertained, and the diagnosis of CADASIL was confirmed through genetic testing, which identified a mutation in the NOTCH3 gene. This paper outlines the aetiopathogenesis, clinical presentation, investigations, and management of CADASIL.