Fatal infantile leukodystrophy: A severe variant of CACH/VWM syndrome, allelic to chromosome 3q27

P. Francalanci, E. Eymard-Pierre, C. Dionisi-Vici, R. Boldrini, F. Piemonte, R. Virgili, G. Fariello, C. Bosman, F. M. Santorelli, O. Boespflug-Tanguy, Enrico Bertini

Research output: Contribution to journalArticlepeer-review


Objective: To describe clinical and neuropathologic studies and linkage analysis on two sisters with a severe form of leukodystrophy. Methods: A detailed study was performed on the second sister. Genotyping markers for chromosome 3, including eight additional markers surrounding the vanishing white matter (VWM) locus, were used. Results: During the first year of life, two sisters developed a severe neurologic condition after an intercurrent infection. It was accompanied by irritability and stupor with rapid loss of their motor abilities. Results of extensive metabolic studies were negative. Brain MRI showed severe and diffuse abnormalities of the encephalic white matter. Neuropathologic examination showed a severe lack of myelin with diffuse vacuolating white matter lesions in the brain, associated with an increased density of oligodendrocytes and a reduced number of astrocytes on morphometric analysis. In sharp contrast, the spinal cord white matter was preserved. The affected sibpairs shared a common haplotype for a broad region in chromosome 3. They were homozygous between markers D3S1565 and D3S3669, including the VWM locus. Conclusions: This condition is an unusual variant of childhood ataxia with diffuse central hypomyelination (CACH)/VWM, with characteristic shrinking and perivascular clustering of astrocytes. Haplotype analysis suggests that this variant is allelic to the VWM locus located on chromosome 3q27.

Original languageEnglish
Pages (from-to)265-270
Number of pages6
Issue number2
Publication statusPublished - Jul 24 2001

ASJC Scopus subject areas

  • Neuroscience(all)


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