title: Adult-onset autosomal dominant leukodystrophy without early autonomic dysfunctions linked to lamin B1 duplication: a phenotypic variant.
abstract: The early presentation of autonomic dysfunctions at the disease onset has been considered the mandatory clinical feature in adult-onset autosomal dominant leukodystrophy, which is a rarely recognised leukodystrophy caused by duplication of the lamin B1 gene. We report the first family with adult-onset autosomal dominant leukodystrophy and lamin B1 duplication, without the distinguishing early-appearing autonomic dysfunctions. Subjects from three consecutive generations of a multi-generational Serbian family affected by adult-onset autosomal dominant leukodystrophy underwent clinical, biochemical, neurophysiological, neuroradiological, and genetic studies. The patients atypically exhibited late autonomic dysfunctions commencing at the disease end-stages in some. Genetic findings of lamin B1 duplication verified adult-onset autosomal dominant leukodystrophy, which was supported also by neuroimaging studies. Exclusively, proton magnetic spectroscopy of the brain revealed a possibility of neuro-axonal damage in the white matter lesions, while magnetic resonance imaging of the spinal cord excluded spinal myelin affection as a required finding in this leukodystrophy. The detection of lamin B1 duplication, even when autonomic dysfunctions do not precede the other symptoms of the disease, proves for the first time that lamin B1-duplicated adult-onset autosomal dominant leukodystrophy may have a phenotypic variant with delayed autonomic dysfunctions. Prior to this report, such a phenotype had been speculated to represent an entity different from lamin B1-duplicated leukodystrophy. Hereby we confirm the underlying role of lamin B1 duplication, regardless of the autonomic malfunction onset in this disorder. It is the only report on adult-onset autosomal dominant leukodystrophy from Southeastern Europe.
authors.affiliation: Medical Faculty, Clinic for Child Neurology and Psychiatry, University of Belgrade, 6A Dr. Subotica Street, Belgrade 11000, Serbia. a.potic@yahoo.com
authors.forename: Ana
authors.initials: A
authors.lastname: Potic
authors.forename: Aleksandra M
authors.initials: AM
authors.lastname: Pavlovic
authors.forename: Graziella
authors.initials: G
authors.lastname: Uziel
authors.forename: Dusko
authors.initials: D
authors.lastname: Kozic
authors.forename: Jelena
authors.initials: J
authors.lastname: Ostojic
authors.forename: Attilio
authors.initials: A
authors.lastname: Rovelli
authors.forename: Nadezda
authors.initials: N
authors.lastname: Sternic
authors.forename: Mladen
authors.initials: M
authors.lastname: Bjelan
authors.forename: Elisa
authors.initials: E
authors.lastname: Sarto
authors.forename: Daniela
authors.initials: D
authors.lastname: Di Bella
authors.forename: Franco
authors.initials: F
authors.lastname: Taroni
mesh_terms: D000328:Adult; D017668:Age of Onset; D001341:Autonomic Nervous System / Q000503:physiopathology*; D001921:Brain / Q000473:pathology; D004247:DNA / Q000235:genetics; D005091:Exons / Q000235:genetics; D005190:Family; D005260:Female; D020440:Gene Duplication; D005838:Genotype; D020279:Hereditary Central Nervous System Demyelinating Diseases / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D034921:Lamin Type B / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D055771:Serbia; D013534:Survival
chemical_list: D034921:Lamin Type B; D004247:DNA