Abstract
Objectives: Using a family study design, we describe the motor and nonmotor phenotype in probands with LRRK2 G2019S mutations and family members and compare these individuals to patients with idiopathic Parkinson disease (iPD) and unrelated controls. Methods: Probands with G2019S mutations and their first-degree relatives, subjects with iPD, and unrelated control subjects were identified from 4 movement disorders centers. All underwent neurologic examinations and tests of olfaction, color vision, anxiety, and depression inventories. Results: Tremor was more often a presenting feature among 25 individuals with LRRK2- associated PD than among 84 individuals with iPD. Subjects with LRRK2-PD had better olfactory identification compared with subjects with iPD, higher Beck Depression Inventory scores, and higher error scores on Farnsworth-Munsell 100-Hue test of color discrimination. Postural or action tremor was more common among 29 nonmanifesting mutation carriers compared with 53 noncarriers within the families. Nonparkinsonian family members had higher Unified Parkinson's Disease Rating Scale motor scores, more constipation, and worse color discrimination than controls, regardless of mutation status. Conclusions: Although tremor is a more common presenting feature of LRRK2-PD than iPD and some nonmotor features differed in degree, the phenotype is largely overlapping. Postural or action tremor may represent an early sign. Longitudinal evaluation of a large sample of nonmanifesting carriers will be required to describe any premotor phenotype that may allow early diagnosis.
| Original language | English |
|---|---|
| Journal | Neurology |
| Volume | 77 |
| Issue number | 4 |
| Pages (from-to) | 325-333 |
| Number of pages | 9 |
| ISSN | 0028-3878 |
| DOIs | |
| Publication status | Published - 26.07.2011 |
Funding
Dr. Marras has served as a consultant for Solvay Pharmaceuticals, Inc.; and has received research support from Merck Serono, the National Parkinson Foundation, Parkinson Study Group, Parkinson Disease Foundation, Michael J Fox Foundation, and the Canadian Institutes of Health Research. Dr. Schuele receives research support from the California Institute for Regenerative Medicine, the Blume Foundation, and the Parkinson's Alliance. Dr. Munhoz reports no disclosures. Dr. Rogaeva receives research support from the Canadian Institutes of Health Research and the Ontario Research Fund. Dr. Langston serves on scientific advisory boards for Teva Pharmaceutical Industries Ltd., Merck Serono, NeuroNova, the Michael J Fox Foundation, and Elan Corporation; has received speaker honoraria from Teva Pharmaceutical Industries Ltd., Parkinson's Resources of Oregon, and Northwest Parkinson's; is listed as an author on patents re: Use of nicotine to treat L-dopa dyskinesias, High-throughput screening for anti-aggregation small molecules to block alpha-synuclein aggregation, Electrophysiological approach using heart rate variability to screen for pre-motor PD, and Use of agents that block GBA activity to treat PD; serves as a consultant for Elan Corporation, Teva Pharmaceutical Industries Ltd., and Lundbeck Inc.; serves on the speakers' bureau for Teva Pharmaceutical Industries Ltd.; receives royalties from sales of a psychometric testing tool (Cognistat), and has received research support from the US Department of Defense, the NIH/NIEHS, California Institute for Regenerative Medicine, the Michael J Fox Foundation, and The Blume Foundation/Stanford University. Dr. Kasten has received funding for travel from the Melvin Yahr Foundation and receives research support from the German Research Foundation (DFG). C. Meaney reports no disclosures. Dr. Klein has received speaker honoraria from GlaxoSmithKline, Boehringer Ingelheim, Merz Pharmaceuticals, LLC, and Orion Corporation; serves on the editorial boards of Neurology® , Movement Disorders , and Parkinson's Disease ; serves as a consultant for Centogene, Boehringer Ingelheim, and Link Medicine; and receives research support from the German Research Foundation (DFG), intramural funding from the University of Lübeck, the Volkswagen Foundation, the Possehl Foundation, the Hermann and Lilly Schilling Foundation, and the Fritz Thyssen Foundation. Dr. Wadia reports no disclosures. Dr. Lim has received speaker honoraria from Boehringer Ingelheim, GlaxoSmithKline, Novartis, and Roche; serves as an Associate Editor for Neurology Asia ; serves as a consultant for GlaxoSmithKline and Novartis; and has received research support from the University of Malaya. Dr. Chuang reports no disclosures. Dr. Zadikof has served on speakers' bureaus for and received speaker honoraria from Allergan, Inc., Teva Pharmaceutical Industries Ltd., Lundbeck Inc., and Ipsen; receives research support from Solvay Pharmaceuticals, Inc., the Michael J Fox Foundation, the Dystonia Medical Research Foundation, the National Parkinson Foundation, and the NIH; and has served as an expert witness in a medico-legal case. Dr. Steeves and Dr. Prakash report no disclosures. Dr. de Bie has received funding for travel from Medtronic, Inc. and Abbott; and has received research support from Medtronic, Inc., ZonMw Doelmatigheid, Het Internationaal Parkinson Fonds, Parkinson Vereniging, and Het Prinses Beatrix Fonds. Dr. Adeli reports no disclosures. Dr. Thomsen received unrestricted fellowship funding from Boehringer Ingelheim. Dr. Johansen reports no disclosures. Dr. Teive serves on the editorial boards of Parkinsonism and Related Disorders and Arquivos de Neuro-Psiquiatria . A. Asante and W. Reginold report no disclosures. Dr. Lang has served on scientific advisory boards for Abbott, Allon Therapeutics, Inc., Biovail Corporation, Boehringer Ingelheim, Cephalon, Inc., Ceregene, Eisai Inc., Medtronic, Inc. Lundbeck Inc., NeuroMolecular Pharmaceuticals, Novartis, Merck Serono, Solvay Pharmaceuticals, Inc., TaroPharma, and Teva Pharmaceutical Industries Ltd.; has received speaker honoraria from GlaxoSmithKline and UCB; receives/has received research support from the Canadian Institutes of Health Research, the Dystonia Medical Research Foundation, the Michael J Fox Foundation, the National Parkinson Foundation, and the Ontario Problem Gambling Research Centre; and has served as an expert witness in cases related to the welding industry.
