title: A family with Parkinsonism, essential tremor, restless legs syndrome, and depression.
abstract: BACKGROUND
  Previous epidemiologic and genetic studies have suggested a link between Parkinson disease (PD), essential tremor (ET), and restless legs syndrome (RLS).
  
  
  METHODS
  We describe the clinical, PET, and pathologic characteristics of an extensive kindred from Arkansas with hereditary PD, ET, and RLS. The pedigree contains 138 individuals. Sixty-five family members were examined neurologically up to 3 times from 2004 to 2010. Clinical data were collected from medical records and questionnaires. Genetic studies were performed. Five family members underwent multitracer PET. Two individuals with PD were examined postmortem.
  
  
  RESULTS
  Eleven family members had PD with generally mild and slowly progressive symptoms. Age at onset was between 39 and 74 years (mean 59.1, SD 13.4). All individuals treated with l-dopa responded positively. Postural or action tremor was present in 6 individuals with PD, and in 19 additional family members. Fifteen persons reported symptoms of RLS. PET showed reduced presynaptic dopamine function typical of sporadic PD in a patient with PD and ET, but not in persons with ET or RLS. The inheritance pattern was autosomal dominant for PD and RLS. No known pathogenic mutation in PD-related genes was found. Fourteen of the family members with PD, ET, or RLS had depression. Neuropathologic examination revealed pallidonigral pigment spheroid degeneration with ubiquitin-positive axonal spheroids, TDP43-positive pathology in the basal ganglia, hippocampus, and brainstem, and only sparse Lewy bodies.
  
  
  CONCLUSIONS
  Familial forms of PD, ET, RLS, and depression occur in this family. The genetic cause remains to be elucidated.
authors.affiliation: Department of Neurology, Mayo Clinic Jacksonville, 4500 San Pablo Road, Jacksonville, FL 32224, USA. Wszolek.Zbigniew@mayo.edu
authors.forename: A
authors.initials: A
authors.lastname: Puschmann
authors.forename: R F
authors.initials: RF
authors.lastname: Pfeiffer
authors.forename: A J
authors.initials: AJ
authors.lastname: Stoessl
authors.forename: R
authors.initials: R
authors.lastname: Kuriakose
authors.forename: J L
authors.initials: JL
authors.lastname: Lash
authors.forename: J A
authors.initials: JA
authors.lastname: Searcy
authors.forename: A J
authors.initials: AJ
authors.lastname: Strongosky
authors.forename: C
authors.initials: C
authors.lastname: Vilariño-Güell
authors.forename: M J
authors.initials: MJ
authors.lastname: Farrer
authors.forename: O A
authors.initials: OA
authors.lastname: Ross
authors.forename: D W
authors.initials: DW
authors.lastname: Dickson
authors.forename: Z K
authors.initials: ZK
authors.lastname: Wszolek
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins / Q000378:metabolism; D003863:Depression / Q000150:complications* / Q000000981:diagnostic imaging / Q000235:genetics; D000072159:Dynactin Complex; D020329:Essential Tremor / Q000150:complications* / Q000000981:diagnostic imaging / Q000235:genetics; D039603:Eukaryotic Initiation Factor-4G / Q000235:genetics; D005192:Family Health; D005260:Female; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008137:Longitudinal Studies; D008297:Male; D008609:Mental Status Schedule; D008869:Microtubule-Associated Proteins / Q000235:genetics; D008875:Middle Aged; D020734:Parkinsonian Disorders / Q000150:complications* / Q000000981:diagnostic imaging / Q000235:genetics; D049268:Positron-Emission Tomography / Q000379:methods; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D012148:Restless Legs Syndrome / Q000150:complications* / Q000000981:diagnostic imaging / Q000235:genetics; D051844:alpha-Synuclein / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D000072159:Dynactin Complex; D039603:Eukaryotic Initiation Factor-4G; D008869:Microtubule-Associated Proteins; C497604:SNCA protein, human; D051844:alpha-Synuclein; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases