Intra-familial phenotypic heterogeneity in adult onset vanishing white matter disease.
Clinical Neurology and Neurosurgery. 2008-12-01; 110(10): 1068-1071
DOI: 10.1016/j.clineuro.2008.08.003
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1. Clin Neurol Neurosurg. 2008 Dec;110(10):1068-71. doi:
10.1016/j.clineuro.2008.08.003. Epub 2008 Oct 8.
Intra-familial phenotypic heterogeneity in adult onset vanishing white matter
disease.
Damon-Perriere N(1), Menegon P, Olivier A, Boespflug-Tanguy O, Niel F, Creveaux
I, Dousset V, Brochet B, Goizet C.
Author information:
(1)CHU Bordeaux, Fédération des Neurosciences Cliniques, Hôpital Pellegrin, 33076
Bordeaux, France.
Vanishing white matter (VWM) disease, also known as childhood ataxia with central
nervous system hypomyelination (CACH) syndrome, is an autosomal recessive
transmitted leukodystrophy. Classically characterised by early childhood onset,
adult onset formed with slower progression have been recently recognized. The
course of neurological impairment is usually progressive with possible occasional
episodes of acute deterioration following febrile illnesses or head trauma.
Neurological features are dominated by cerebellar ataxia and spasticity with
relatively preserved mental abilities. Brain MRI shows diffuse abnormal signal of
the cerebral white matter and cystic degeneration. Mutations in one of the genes
coding for the five subunits of the translation factor eukaryotic initiation
factor 2B (eIF2B) have been identified. We report here on two sisters affected by
adult onset VWM with variable phenotypic expression. The proband is remarkable by
the very late age of the disease onset (age of 42). A homozygous p.Arg113His
mutation in the eIF2Bvarepsilon gene was identified. This mutation had been
recurrently associated with adult onset VWM establishing phenotype-genotype
correlations. We will show an important intra-familial phenotypic variability and
discuss it in the light of recent molecular progresses. External precipitating
factors are contributing for some of the differences observed.
DOI: 10.1016/j.clineuro.2008.08.003
PMID: 18845387 [Indexed for MEDLINE]