CADASIL — Frequently asked questions

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy. It is a hereditary disease of the small blood vessels of the brain caused by mutations in the NOTCH3 gene. Read the full overview →

CADASIL is caused by pathogenic variants in the NOTCH3 gene on chromosome 19. Most disease-causing variants alter cysteine residues in the EGFr domains of the NOTCH3 protein, leading to misfolding, accumulation in vessel walls, and progressive damage to the brain's small arteries.

Yes — CADASIL is inherited in an autosomal dominant pattern. Each child of a parent with CADASIL has a 50% chance of inheriting the pathogenic NOTCH3 variant. Both males and females are affected equally. Rare de novo variants have been described.

Reported clinical prevalence is roughly 2–5 per 100,000 adults, but population genomic data suggest pathogenic NOTCH3 variants are more common — possibly approaching 1 in 300 to 1 in 400 people, with many carrying milder, late-onset variants.

The core symptoms are migraine with aura (often beginning in the 20s–30s), recurrent ischemic strokes and TIAs (typically in the 40s–60s), mood disturbance and apathy, and progressive subcortical vascular cognitive impairment. Gait disturbance is common in advanced disease. Full symptoms guide →

Migraine in CADASIL is often migraine with aura, sometimes with prolonged or atypical features (visual, sensory, language, or hemiplegic). About 30–40% of CADASIL patients experience migraine with aura — frequently as the earliest symptom.

Migraine with aura often appears in the 20s–30s. Strokes and TIAs typically begin in the 40s–60s. Cognitive and mood changes can appear at any age, but become more prominent over time. There is wide variability between individuals — even within the same family.

CADASIL can lead to vascular cognitive impairment, which in advanced cases meets criteria for vascular dementia. But CADASIL is fundamentally a genetic small-vessel arteriopathy — dementia is one of its later manifestations, not the disease itself.

Diagnosis combines clinical pattern recognition, brain MRI, and NOTCH3 genetic testing. Skin biopsy with electron microscopy may be used when genetic results are inconclusive. Full diagnostic pathway →

Confluent T2/FLAIR white-matter hyperintensities — particularly in the anterior temporal poles and external capsules — together with lacunar infarcts, cerebral microbleeds (on SWI/GRE), and progressive atrophy. The corpus callosum and U-fibers are typically spared.

No — and CADASIL is often misdiagnosed as MS because both can produce white-matter lesions on MRI. CADASIL is a genetic small-vessel disease defined by NOTCH3 mutations; MS is an autoimmune demyelinating disease. MRI patterns differ — CADASIL classically involves the anterior temporal poles and external capsules and spares the corpus callosum and U-fibers, and CSF studies in CADASIL are negative for oligoclonal bands.

If you have symptoms suggestive of CADASIL or a strong family history, discuss testing with a neurologist and a genetic counsellor. Predictive testing in asymptomatic adult relatives is appropriate, deeply personal, and should be paired with pre- and post-test genetic counselling.

GOM is a pathognomonic ultrastructural finding in CADASIL — abnormal deposits in the basement membrane around vascular smooth muscle cells, visible on electron microscopy of small arteries (often sampled via skin biopsy).

There is currently no disease-modifying therapy for CADASIL. However, several therapeutic strategies — including antisense oligonucleotides targeting mutant NOTCH3 — are in early development. Excellent supportive care and aggressive vascular risk factor management can meaningfully improve outcomes. Treatment overview →

CADASIL care is typically led by a neurologist — often a stroke specialist or neurogeneticist — in collaboration with a genetic counsellor, primary care, and mental-health and rehabilitation professionals as needed.

Yes — meaningfully. Aggressive control of vascular risk factors (especially blood pressure and smoking), regular aerobic exercise, Mediterranean-style nutrition, sleep optimization, and treatment of mood disturbance are all evidence-informed components of care.

Triptans are not absolutely contraindicated, but caution is warranted given their vasoconstrictive profile and the underlying small-vessel arteriopathy. Decisions should be individualized in consultation with a CADASIL-aware clinician.

Antiplatelet therapy (typically aspirin) is commonly used after ischemic events in CADASIL — but must be balanced against the recognized risk of intracerebral hemorrhage from microbleeds. Long-term dual antiplatelet therapy is generally avoided. Anticoagulation is reserved for clear indications. Decisions should be individualized.

Penetrance is essentially complete with age, but expressivity is highly variable. Mild variants, late onset, or earlier deaths from unrelated causes can make the disease appear to skip generations even though the genetic variant is still present.

Each child has a 50% chance of inheriting the variant. Children who inherit the variant will eventually develop the disease — though age of onset and severity vary widely.

Many people with CADASIL work, raise families, and live full lives — particularly with early diagnosis, good care, and lifestyle support. The disease course is highly variable. Family planning decisions are personal and should be supported by genetic counselling.

Variable. Lifespan is typically reduced compared to the general population, but many people live for decades after diagnosis with good function — especially when vascular risk factors are aggressively managed and supportive care is in place.

Several therapeutic strategies are in early-stage development, including antisense oligonucleotides and other gene-targeted approaches. Natural-history studies and registries are active. Patients and families can ask their neurologist or contact us for current opportunities. Research overview →