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[CADASIL: a case with clinical, radiological, histological and genetic diagnoses]
I J Posada1, I García-Morales, M A Martínez
1Servicio de Neurología, Hospital 12 de Octubre, Madrid, Spain. iposada@hdoc.insalud.es
Insights
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare genetic brain disorder. A novel NOTCH3 gene mutation, C406T (Arg110Cys), was identified in a patient presenting typical CADASIL symptoms.
Area of Science:
- Neuroscience
- Genetics
- Pathology
Background:
- Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare inherited cerebrovascular disorder.
- Clinical manifestations include migraine with aura, transient ischemic attacks, and subcortical dementia.
- Neuroimaging reveals deep cerebral infarcts and leukoencephalopathy; neuropathology shows vascular smooth muscle cell degeneration.
Observation:
- A patient with classic CADASIL clinical, neuroimaging, and pathological features was studied.
- Genetic analysis identified a C406T (Arg110Cys) missense mutation in the NOTCH3 gene.
Findings:
- The identified C406T (Arg110Cys) mutation in the NOTCH3 gene is linked to CADASIL pathogenesis.
- This finding expands the known genetic spectrum of CADASIL.
Implications:
- This case contributes to understanding CADASIL genetics, particularly in populations with limited reported families.
- Further research into NOTCH3 mutations can improve diagnosis and potential therapeutic strategies for CADASIL.
Abstract:
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare inherited cerebrovascular disease. The onset of clinical symptoms occurs with migraine with aura, transient ischemic attacks, recurrent subcortical ischemic infarcts, neuropsychiatric changes reaching subcortical dementia. Brain magnetic resonance images show multiple deep cerebral infarcts in white matter and basal ganglia and diffuse leukoencephalopathy. Neuropathologic hallmark consists of deposition of small electron dense granular patches related to the basement membrane of vascular smooth muscle cells with degeneration of smooth muscle cells and media and luminal obliteration. Recently, the genetic characteristics of this disorder have been reported. Missense mutations in notch3 gene localized in chromosome 19 are involved in its pathogenesis. Only three families from Spain have been reported. Here we describe a patient with typical clinical symptoms, neuroimaging and pathology of CADASIL. C406T (Arg110Cys) mutation in notch3 gene was found. We comment on the clinical symptoms of different members of the patient's family.