CADASIL is a rare inherited genetic disorder that affects the small blood vessels in the brain. It can lead to various neurological symptoms, including strokes and cognitive decline, and is a condition for understanding genetic contributions to cerebrovascular diseases.
Understanding CADASIL
Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy, or CADASIL, primarily impacts the brain’s small blood vessels. This damage impairs blood flow, leading to progressive tissue damage within the brain. Its effects tend to worsen over time.
The condition often manifests through recurrent subcortical ischemic strokes, which affect the deeper parts of the brain. It can also cause cognitive impairment that progresses to dementia. Other common features include migraines, particularly with aura, and mood disturbances like depression and apathy.
The Numbers: Unpacking Its Rarity
Precise global prevalence figures for CADASIL are challenging to obtain due to varying diagnostic practices and potential underdiagnosis. Estimates suggest a prevalence ranging from approximately 1 to 9 cases per 100,000 individuals. For example, in Europe, prevalence has been estimated between 1 in 50,000 and 1 in 25,000 people. Some studies indicate a prevalence of at least 4.1 per 100,000 adults.
Despite its rarity, CADASIL is the most common inherited cause of stroke and vascular dementia in adults. Recent large-scale genomic studies suggest a higher prevalence of pathogenic gene variants than previously thought, particularly among individuals of Asian descent.
The Genetic Basis of CADASIL’s Rarity
CADASIL is caused by mutations in the NOTCH3 gene. This gene provides instructions for making the NOTCH3 receptor protein, which plays a role in the function of vascular smooth muscle cells in the brain’s small arteries.
It is an autosomal dominant inherited disorder. This means a person only needs to inherit one copy of the mutated NOTCH3 gene from a parent to develop the condition. More than 95% of CADASIL cases are attributed to these NOTCH3 gene mutations. Over 280 distinct pathogenic mutations have been identified.
Diagnostic Challenges and Prevalence
Diagnosing CADASIL can be challenging. Its symptoms, such as stroke, cognitive decline, and migraines, overlap with more common neurological conditions, leading to misdiagnosis or delayed diagnosis. Some patients are initially diagnosed with conditions like multiple sclerosis.
Definitive diagnosis typically involves specialized tests, primarily genetic testing for NOTCH3 gene mutations. Magnetic Resonance Imaging (MRI) findings, which often show characteristic white matter changes and subcortical infarcts, also aid in diagnosis. Genetic testing can be expensive, and a small percentage of individuals with classic CADASIL symptoms may have negative genetic test results, possibly due to unidentified mutations. These diagnostic complexities suggest CADASIL may be underreported, impacting its known prevalence.