Clinical variability of the cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy phenotype in two siblings of a large family showing the same mutation

Abstract

A 44-year-old Albanian male was consulted and diagnosed with dementia. His magnetic resonance imaging suggested diffuse white matter changes. The suspicion of cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) was raised, and a genetic analysis confirmed such a suspicion through uncovering a pathogenic mutation at the level of exon 4 (c.475C>T) of chromosome 19. The patient came from a large family of 13 children, all of whom underwent clinical, genetic, and imaging examination. The pathogenic mutation was found present only in his eldest sister (50 years old), and she presented also very suggestive signs of CADASIL in her respective imaging study, but without any clinically significant counterpart. All other siblings were free from clinical and radiological signs of the disorder. Our opinion was that we were dealing with a mutation showing a very low level of penetrance, with only two siblings affected in a large Albanian family with 13 children.

What factors determine phenotype of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)? Considerations in the context of a novel pathogenic R110C mutation in the NOTCH3 gene

“…In some of these reports the authors emphasized phenotypic variability of the disease even among family members with the same mutation [18] or monozygotic twins [11]. Our article on a CADASIL family with a novel R110C mutation joins that group of publications.…”

Tension Headaches and Vertigo in a Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy Patient

“…[2,13] Tension headaches are neither included in the types of CADASIL-related headaches [13] nor they receive a score in the widely used CADASIL scale. [14] However, they have been described in occasional patients [15] and, in some families with the R544C mutation, they are the prevailing type of headache (87.5%), with migraine being extremely rare. [16] Vertigo seems to be a rare (<7%) symptom in CADASIL [17] but may occur in occasional patients, even mimicking Meniere's disease.…”