Adult-onset genetic leukoencephalopathies: A MRI pattern-based approach in a comprehensive study of 154 patients
Open Access
- 19 December 2014
- journal article
- research article
- Published by Oxford University Press (OUP) in Brain
- Vol. 138 (2), 284-292
- https://doi.org/10.1093/brain/awu353
Abstract
Inherited white matter diseases are rare and heterogeneous disorders usually encountered in infancy. Adult-onset forms are increasingly recognized. Our objectives were to determine relative frequencies of genetic leukoencephalopathies in a cohort of adult-onset patients and to evaluate the effectiveness of a systematic diagnostic approach. Inclusion criteria of this retrospective study were: (i) symmetrical involvement of white matter on the first available brain MRI; (ii) age of onset above 16 years. Patients with acquired diseases were excluded. Magnetic resonance imaging analysis identified three groups (vascular, cavitary and non-vascular/non-cavitary) in which distinct genetic and/or biochemical testing were realized. One hundred and fifty-four patients (male/female = 60/94) with adult-onset leukoencephalopathies were identified. Mean age of onset was 38.6 years. In the vascular group, 41/55 patients (75%) finally had a diagnosis [including CADASIL (cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy, n = 32) and COL4A1 mutation, n = 7]. In the cavitary group, 13/17 (76%) patients had a diagnosis of EIF2B-related disorder. In the third group (n = 82), a systematic biological screening allowed a diagnosis in 23 patients (28%) and oriented direct genetic screening identified 21 additional diseases (25.6%). Adult-onset genetic leukoencephalopathies are a rare but probably underestimated entity. Our study confirms the use of a magnetic resonance imaging-based classification with a final diagnosis rate of 64% (98/154) cases.This publication has 27 references indexed in Scilit:
- A practical approach to diagnosing adult onset leukodystrophiesJournal of Neurology, Neurosurgery & Psychiatry, 2013
- Adult-onset cerebral X-linked adrenoleukodystrophy with major contrast-enhancement mimicking acquired diseaseClinical Neurology and Neurosurgery, 2013
- Krabbe disease in adults: phenotypic and genotypic update from a series of 11 cases and a reviewJournal of Inherited Metabolic Disease, 2012
- FXTASNeurology, 2012
- Teaching Neuro Images : Oculodentodigital dysplasiaNeurology, 2012
- Leukoencephalopathies in Mitochondrial Disorders: Clinical and MRI FindingsJournal of Neuroimaging, 2012
- Histoire naturelle des leucodystrophies avec mutation EIF2B : étude rétrospective multicentrique de 24 cas adultesRevue Neurologique, 2011
- The burden of inherited leukodystrophies in childrenNeurology, 2010
- The effect of genotype on the natural history of eIF2B-related leukodystrophiesNeurology, 2004
- The phenotypic spectrum of CADASIL: Clinical findings in 102 casesAnnals of Neurology, 1998