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Neurologic features and genotype-phenotype correlation in Wolfram syndrome†
Article first published online: 28 DEC 2010
Copyright © 2010 American Neurological Association
Annals of Neurology
Volume 69, Issue 3, pages 501–508, March 2011
How to Cite
Chaussenot, A., Bannwarth, S., Rouzier, C., Vialettes, B., Mkadem, S. A. E., Chabrol, B., Cano, A., Labauge, P. and Paquis-Flucklinger, V. (2011), Neurologic features and genotype-phenotype correlation in Wolfram syndrome. Ann Neurol., 69: 501–508. doi: 10.1002/ana.22160
- Issue published online: 28 MAR 2011
- Article first published online: 28 DEC 2010
- Manuscript Accepted: 12 JUL 2010
- Manuscript Revised: 11 JUL 2010
- Manuscript Received: 22 MAR 2010
Wolfram syndrome (WS) is a rare neurodegenerative disorder characterized by juvenile-onset diabetes mellitus and optic atrophy. Our aim was to describe the nature and the frequency of the neurologic manifestations, which had been poorly studied until now.
We performed a detailed clinical study with genotype-phenotype correlation in a series of 59 patients with WS.
The onset of neurologic symptoms, with a median age of 15 years, was much earlier than previously reported. Cognitive impairment, which was not frequent in previous reports, was observed in 32% of patients with neurologic signs. Like epilepsy, it was mainly found in patients who developed neurologic signs before 15 years of age. In contrast to previous series, we also found malformations of cortical development on magnetic resonance imaging in epileptic children and white matter involvement, including diffuse leukoencephalopathy, in adult patients. We identified 109 mutated alleles corresponding to 56 different mutations of the WFS1 gene, among which 10 were novel. Homozygosity or compound heterozygosity for missense mutation does not seem to influence the age of onset and the occurrence of neurologic complications. However, an interesting point concerns a possible correlation between the location of the mutations and the development of the neurologic manifestations.
This series concerns the largest cohort of WS patients reported to date. It illustrates the wide variety of neurologic signs in this syndrome and the necessity of rapid therapeutic coverage to improve the prognosis. Ann Neurol 2010.