CADASIL syndrome in a large Turkish kindred caused by the R90C mutation in the Notch3 receptor

Area of Science:

• Genetics
• Neurology
• Molecular Biology

Background:

• Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetic, adult-onset neurologic disorder.
• It is characterized by recurrent strokes and dementia, typically diagnosed through clinical features and cerebral MRI findings.
• Mutations in the Notch3 gene are identified as the causative agent of CADASIL.

Observation:

• A Turkish family with four generations and 12 affected individuals exhibiting typical CADASIL symptoms was studied.
• Genetic analysis revealed the R90C mutation in the Notch3 gene in affected family members.
• Two young mutation carriers presented with migraine without aura as their sole initial symptom, preceding other clinical signs or MRI abnormalities.

Findings:

• The R90C mutation in the Notch3 gene was identified in affected individuals of the Turkish family.
• Migraine without aura was observed as an early, isolated symptom in young CADASIL mutation carriers.
• The absence of MRI abnormalities in these early-stage patients complicates diagnosis without genetic screening.

Implications:

• Migraine without aura should be considered a potential early indicator of CADASIL, particularly in individuals with a family history.
• Molecular screening for Notch3 mutations offers a rapid and accurate diagnostic method for CADASIL.
• Early diagnosis through genetic testing can facilitate timely intervention and management of CADASIL.