CADASIL with Atypical Clinical Symptoms, Magnetic Resonance Imaging, and Novel Mutations: Two Case Reports and a Review of the Literature

Abstract

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary microangiopathy with adult onset caused by a missense mutation in the NOTCH3 gene in chromosome 19p13. It presents with autosomal dominant arteriopathy, subcortical infarctions, and leukoencephalopathy. Its common clinical presentations are seen as recurrent strokes, migraine or migraine-like headaches, progressive dementia, pseudobulbar paralysis, and psychiatric conditions. Two patients with CADASIL syndrome, whose diagnosis was made based on clinical course, age of onset, imaging findings, and genetic assays in the patients and family members, are presented here because of new familial polymorphisms. The first patient, with cerebellar and psychotic findings, had widespread non-confluent hyperintense lesions as well as moderate cerebellar atrophy in cranial magnetic resonance scanning. The other patient, with headache, dizziness, and forgetfulness, had gliotic lesions in both cerebral hemispheres. CADASIL gene studies revealed a new polymorphism in exon 33 in the first patient. In the other patient, the NOTCH3 gene was identified as a new variant of p.H243P (c.728A > C heterozygous). By reporting a family presenting with various clinical symptoms in the presence of new polymorphisms, we emphasize that CADASIL syndrome may present with various clinical courses and should be considered in differential diagnoses.

Keywords: CADASIL; Genetic testing; Headache; MRI; NOTCH3; Small vessel disease.