"CADASIL coma" in an Italian homozygous CADASIL patient: Comparison with clinical and MRI findings in age-matched heterozygous patients with the same G528C NOTCH3 mutation

Michele Ragno, Luigi Pianese, Manrico Morroni, Gabriella Cacchiò, Antonio Manca, Fabio Di Marzio, Serena Silvestri, Cristina Miceli, Maria Scarcella, Marco Onofrj, Luigi Trojano

Research output: Contribution to journalArticle

Abstract

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetic disorder caused by mutations in the NOTCH3 gene, with a striking variability in phenotypic expression. To date, only two homozygous patients have been reported, with divergent phenotypic features. We describe an Italian CADASIL patient, homozygous for G528C mutation, in whom early manifestation of the disease was migraine, but whose clinical evolution was characterized by a reversible acute encephalopathy followed by full recovery ("CADASIL coma"). Clinical evaluation, MR scan, neuropsychological and neurophysiological investigation did not reveal substantial differences between our homozygous patient and her heterozygous relatives sharing the same mutation, or between our patient and a group of heterozygous individuals with the same mutation but from different families. Skin biopsy identified peculiar features in the homozygous patient, with cytoplasmic pseudoinclusions likely containing granular osmiophilic material (GOM) in the vascular smooth muscle cells, but further studies are necessary to substantiate their possible relationships with CADASIL homozygosis. "CADASIL coma" did not seem to be specific of patient's homozygosis, since it was observed in one of her heterozygous relatives, whereas its pathogenesis seems to be related to peculiar constellations of unknown predisposing factors. The present study demonstrated that CADASIL conforms to the classical definition of dominant diseases, according to which homozygotes and heterozygotes for a defect are phenotypically indistinguishable.

Original languageEnglish
Pages (from-to)1947-1953
Number of pages7
JournalNeurological Sciences
Volume34
Issue number11
DOIs
Publication statusPublished - Nov 2013

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Keywords

  • Autosomal dominance
  • CADASIL
  • Homozygosis
  • Migraine
  • Stroke

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Dermatology

Cite this

Ragno, M., Pianese, L., Morroni, M., Cacchiò, G., Manca, A., Di Marzio, F., Silvestri, S., Miceli, C., Scarcella, M., Onofrj, M., & Trojano, L. (2013). "CADASIL coma" in an Italian homozygous CADASIL patient: Comparison with clinical and MRI findings in age-matched heterozygous patients with the same G528C NOTCH3 mutation. Neurological Sciences, 34(11), 1947-1953. https://doi.org/10.1007/s10072-013-1418-5