Journal of Neurology

, Volume 261, Issue 4, pp 768–772 | Cite as

Hereditary diffuse leukoencephalopathy with axonal spheroids: three patients with stroke-like presentation carrying new mutations in the CSF1R gene

  • Carla Battisti
  • Ilaria Di Donato
  • Silvia Bianchi
  • Lucia Monti
  • Patrizia Formichi
  • Alessandra Rufa
  • Ilaria Taglia
  • Alfonso Cerase
  • Maria Teresa Dotti
  • Antonio Federico
Original Communication

Abstract

Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) is an autosomal dominant disorder characterized by white matter neurodegeneration, progressive cognitive decline, and motor symptoms. Histologically, it is characterized by axonal swellings (“spheroids”). To date, over 20 different mutations affecting the tyrosine kinase domain of the protein have been identified in the colony stimulating factor 1 receptor (CSF1R) gene. Our goal is to describe three unrelated Italian patients affected by HDLS and carrying new CSF1R mutations, thus expanding the mutational spectrum and phenotypic presentation. CSF1R gene analysis was performed in 15 patients (age range 25–83 years) with undefined leukoencephalopathy and progressive cognitive decline. In three patients (two males and one female, aged 58, 37, and 48 years, respectively), new heterozygous missense mutations affecting the protein tyrosine kinase domain of the CSF1R gene were detected. In all of these patients, behavioural and cognitive changes were preceded by an ischemic stroke-like episode. A positive family history was present in only one case.

Keywords

HDLS CSF1R Presenile dementia Axonal spheroids Leukoencephalopathy 

Notes

Acknowledgments

This work was supported by a grant from MIUR (Ministero dell’Istruzione, dell’Università e della Ricerca), programmi di ricerca cofinanziati-2009 (MIUR 2009-prot. 20095JPSNA) to MTD.

Conflicts of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Carla Battisti
    • 1
  • Ilaria Di Donato
    • 1
  • Silvia Bianchi
    • 1
  • Lucia Monti
    • 2
  • Patrizia Formichi
    • 1
  • Alessandra Rufa
    • 1
  • Ilaria Taglia
    • 1
  • Alfonso Cerase
    • 2
  • Maria Teresa Dotti
    • 1
  • Antonio Federico
    • 1
  1. 1.Neurology and Neurometabolic Diseases Unit, Department of Medicine, Surgery and NeuroscienceUniversity of SienaSienaItaly
  2. 2.Neuroimaging and Neurointervention Unit, Department of Neurological and Sensorineural SciencesAzienda Ospedaliera Universitaria Senese, Policlinico “Santa Maria alle Scotte”SienaItaly

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