Neurological Sciences

, Volume 34, Issue 11, pp 1947–1953

“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
Original Article

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.

Keywords

CADASIL Autosomal dominance Homozygosis Migraine Stroke 

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Copyright information

© Springer-Verlag Italia 2013

Authors and Affiliations

  • Michele Ragno
    • 1
  • Luigi Pianese
    • 2
  • Manrico Morroni
    • 3
  • Gabriella Cacchiò
    • 1
  • Antonio Manca
    • 4
  • Fabio Di Marzio
    • 1
  • Serena Silvestri
    • 2
    • 5
  • Cristina Miceli
    • 6
  • Maria Scarcella
    • 1
  • Marco Onofrj
    • 7
  • Luigi Trojano
    • 8
  1. 1.Neurology DivisionMazzoni HospitalAscoli PicenoItaly
  2. 2.Molecular Medicine SectionMazzoni HospitalAscoli PicenoItaly
  3. 3.Department of Experimental and Clinical Medicine, Section of Neuroscience and Cell BiologySchool of Medicine, Università Politecnica delle Marche and Electron Microscopy Unit, United HospitalsAnconaItaly
  4. 4.Department of RadiologyItalian National Research Center of AgingAnconaItaly
  5. 5.Doctoral Course in Environmental Sciences and Public HealthSchool of Advanced Studies, University of CamerinoCamerinoItaly
  6. 6.School of Biosciences and BiotechnologyUniversity of CamerinoCamerinoItaly
  7. 7.Dipartimento di Neuroscienze e ImagingUniversità “G.D’Annunzio” Chieti-PescaraChietiItaly
  8. 8.Department of PsychologySecond University of NaplesCasertaItaly

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