title: PSP-CBS with Dopamine Deficiency in a Female with a FMR1 Premutation.
abstract: Premutations in the fragile X mental retardation 1 (FMR1) gene cause fragile X-associated tremor/ataxia syndrome (FXTAS) and FMR1-related primary ovarian insufficiency (POI). Female FMR1 premutation carriers rarely develop motor features. Dual pathology is an emerging phenomenon among FMR1 premutation carriers. Here, we describe a family affected by FMR1-related disorders in which the female index case has developed a rapidly progressive and disabling syndrome of atypical parkinsonism. This syndrome consists of early onset postural instability, echolalia, dystonia, and varying types of apraxia like early onset orobuccal apraxia and oculomotor apraxia. She has also developed supranuclear gaze palsy, increased latency of saccade initiation, and slow saccades. These features are compatible with progressive supranuclear palsy (PSP) of a corticobasal syndrome (CBS) variant. Imaging displays a marked reduction of presynaptic dopaminergic uptake and cerebrospinal fluid analysis showed reduced dopamine metabolism; however, the patient is unresponsive to levodopa. Midbrain atrophy ("hummingbird sign") and mild cerebellar atrophy were found on brain MRI. Her father was affected by a typical FXTAS presentation but also displayed dopamine deficiency along with the hummingbird sign. The mechanisms by which FMR1 premutations predispose to atypical parkinsonism and dopamine deficiency await further elucidation.
authors.affiliation: Department of Neurology and Clinical Neuroscience, Karolinska University Hospital and Karolinska Institutet, 141 86, Stockholm, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Paucar
authors.affiliation: Department of Neurology and Clinical Neuroscience, Karolinska University Hospital and Karolinska Institutet, 141 86, Stockholm, Sweden.
authors.forename: Stanislav
authors.initials: S
authors.lastname: Beniaminov
authors.affiliation: Department of Neurology and Clinical Neuroscience, Karolinska University Hospital and Karolinska Institutet, 141 86, Stockholm, Sweden.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Paslawski
authors.affiliation: Department of Neurology and Clinical Neuroscience, Karolinska University Hospital and Karolinska Institutet, 141 86, Stockholm, Sweden. per.svenningsson@ki.se.
authors.forename: Per
authors.initials: P
authors.lastname: Svenningsson
mesh_terms: D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging; D004298:Dopamine / Q000172:deficiency*; D005190:Family; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D013494:Supranuclear Palsy, Progressive / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000235:genetics*; D019680:Trinucleotide Repeat Expansion
chemical_list: D004298:Dopamine; D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human
keywords: Corticobasal syndrome; Dopamine; FMR1; FXTAS; Fragile X; Progressive supranuclear palsy