title: A familial form of pallidoluysionigral degeneration and amyotrophic lateral sclerosis with divergent clinical presentations.
abstract: We describe a family with a rapidly progressive neurodegenerative disorder characterized by amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) but with unusual neuropathologic features that include pallidoluysionigral degeneration. The proband presented with primary progressive aphasia that evolved into mutism. He subsequently developed dementia with mild disinhibition and parkinsonism and late in the disease showed evidence of motor neuron disease. Two other cases (the proband's mother and maternal uncle) had features of ALS exclusively. All 3 had a young onset (fourth decade) and rapid clinical course, with average time from onset of symptoms to death of 4 years. Postmortem neuropathologic examination of the proband and his uncle showed ALS changes and extensive pallidoluysionigral degeneration without neurofibrillary tangles, ubiquitin inclusions, or detectable abnormalities in the dentate nucleus of the cerebellum. Although this exceptional combination of neuropathologic features has been described in rare cases of sporadic ALS-FTD, no pedigrees have ever been reported. In 2 affected members of this family, we failed to identify mutations in genes associated with weakness, movement disorders, or dementia, including ALS, FTD, selected spinocerebellar ataxias, and Huntington disease. Thus, this disorder may represent a novel autosomal dominantly inherited and rapidly progressive neurodegenerative disorder with a spectrum of clinical presentations but common neuropathologic features.
authors.affiliation: UCLA Department of Neurology, Reed Neurological Research Center, 710 Westwood Plaza, Los Angeles, CA 90095, USA. cpcailliau@mednet.ucla.edu
authors.forename: Carlos
authors.initials: C
authors.lastname: Portera-Cailliau
authors.forename: Carsten
authors.initials: C
authors.lastname: Russ
authors.forename: Robert H
authors.initials: RH
authors.lastname: Brown
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Budson
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Vonsattel
authors.forename: Rebecca D
authors.initials: RD
authors.lastname: Folkerth
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Corbo
mesh_terms: D000328:Adult; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D005192:Family Health; D005260:Female; D005917:Globus Pallidus / Q000473:pathology*; D006801:Humans; D008297:Male; D009434:Neural Pathways / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D013378:Substantia Nigra / Q000473:pathology*; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1
chemical_list: C000606290:SOD1 protein, human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1