title: Adult-onset genetic leukoencephalopathies: a MRI pattern-based approach in a comprehensive study of 154 patients.
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.
authors.affiliation: 1 Département de Neurologie, CHU de Montpellier, 34295 Montpellier, France.
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authors.affiliation: 1 Département de Neurologie, CHU de Montpellier, 34295 Montpellier, France.
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authors.affiliation: 30 Centre de référence maladies rares Leucodystrophies, Service de Neuropédiatrie et des Maladies Métaboliques, AP-HP Hôpital Robert Debré, Paris, France 31 NEUROPROTECT, Inserm U1141, Université Paris Diderot, Sorbonne Paris Cité, Hôpital Robert Debré, Paris, France.
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authors.affiliation: 30 Centre de référence maladies rares Leucodystrophies, Service de Neuropédiatrie et des Maladies Métaboliques, AP-HP Hôpital Robert Debré, Paris, France 31 NEUROPROTECT, Inserm U1141, Université Paris Diderot, Sorbonne Paris Cité, Hôpital Robert Debré, Paris, France.
authors.forename: Odile
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authors.lastname: Boespflug Tanguy
authors.affiliation: 1 Département de Neurologie, CHU de Montpellier, 34295 Montpellier, France labauge@yahoo.fr.
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mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D002561:Cerebrovascular Disorders / Q000235:genetics / Q000473:pathology; D005260:Female; D005602:France; D006801:Humans; D056784:Leukoencephalopathies / Q000235:genetics* / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D066127:White Matter / Q000473:pathology; D055815:Young Adult
keywords: MRI; genetic; leukodystrophy; leukoencephalopathies; metabolic