Clinical and Genetic Characteristics of Participants with Juvenile PD: The CORE-PD Study (IN10-2.001)

Objective: We describe all Juvenile Parkinson9s Disease (JPD) probands who were recruited through the CORE-PD study. Background JPD is exceptionally rare, seldom reported, and defined as disease age at onset (AAO) Design/Methods: Eleven hundred and three individuals with early-onset PD (defined as AAO SNCA , PRKN , PINK1 , DJ1 , LRRK2 and GBA . Results: Twenty probands (1.8%) reported AAO PRKN carriers, two were PRKN heterozygotes, two carried heterozygous GBA mutations (one L444P and one N370S) and one carried the LRRK2 G2019S mutation. Only four (20%) reported a family history of PD in a first degree relative, all of whom carried PRKN mutations (two compound heterozygotes and two heterozygotes). Of these four probands, two had a family history of JPD in siblings (one heterozygote with AAO=16 and one compound heterozygote with AAO=12), each with a similar genotype to proband. None of the 66 PRKN mutation carriers with disease onset>20 had a sibling with JPD. Conclusions: JPD is extremely rare among EOPD. While identifiable genetic risk factors are common, first degree family history of PD is present in a minority. Supported by: Funded by NIH NS36630, UL1 RR024156 (K.S.M.), NS050487, NS060113 (L.N.C.), the Parkinson9s Disease Foundation (K.S.M., S.F., and L.N.C.), P50 NS039764 (W.K.S) and NS36960 (H.P). RNA is a Brookdale Foundation Leadership in Aging Fellow. Disclosure: Dr. Alcalay has nothing to disclose. Dr. Rosado has nothing to disclose. Dr. Mejia-Santana has nothing to disclose. Dr. Orbe-Reilly has nothing to disclose. Dr. Caccappolo has nothing to disclose. Dr. Tang has nothing to disclose. Dr. Ruiz has nothing to disclose. Dr. Ross has nothing to disclose. Dr. Verbitsky has nothing to disclose. Dr. Kisselev has nothing to disclose. Dr. Louis has nothing to disclose. Dr. Comella has received personal compensation for activities with Ipsen, Merz Pharma, Allergan, Inc., and NuPathe. Dr. Comella has received research support from Ipsen, Merz Pharma, Allergan, Inc., the National Institutes of Health, and the Dystonia Study Group. Dr. Colcher has nothing to disclose. Dr. Jennings has received personal compensation for activities with Lundbeck Research USA as a speaker. Dr. Nance has received research support from Medivation, Santhera, Juvantia, Neurosearch Sweden, Pfizer Inc, Neuraltus, Impax, and Schwarz Biosciences. Dr. Bressman has received license fee payments from Beth Israel/Mount Sinai/Athena. Dr. Scott has nothing to disclose. Dr. Tanner has received personal compensation for activities with Impax Pharmaceuticals, Allergan, Inc. & Genentech, Inc. as a consultant. Dr. Tanner has received research support from Michael J. Fox Foundation, Department of Defense, Parkinson9s Disease Foundation, Parkinson9s Institute, Unity Walk and Brin Foundation. Dr. Andrews has nothing to disclose. Dr. Waters has received personal compensation for activities with Boehringer Ingelheim Pharmaceuticals, Inc., Novartis, and Teva Neuroscience as a speaker. Dr. Fahn has received personal compensation for activities with Intec Pharma, Merz Pharma, Oxford Biomedica, RJG Foundation, IMPAX Pharmaceuticals, and Lundbeck as a consultant. Dr. Fahn has received personal compensation in an editorial capacity for Elsevier and Springer. Dr. Cote has nothing to disclose. Dr. Frucht has received personal compensation for activities with UCB Pharma. Dr. Ford has received personal compensation for activities with Novartis and Medtronic, Inc. Dr. Rezak has received personal compensation for activities with Medtronic, Teva, Novartis, Allergan, Smih-Klein, Boehringer-Ingleheim, and UBC as a speaker. Dr. Novak has nothing to disclose. Dr. Friedman has received personal compensation for activities with Teva Neuroscience, Boehringer Ingelheim Pharmaceuticals, Inc., Genzyme Corporation, Adix, Roche Diagnostics Corporation. Dr. Friedman has received research support from Teva Neuroscience, Merck & Co., Inc., EMD Serono, Schering-Plough Corporation, National Institutes of Health, Michael J. Fox Foundation, GE Healthcare and Acadia. Dr. Pfeiffer has received personal compensation for activities with UCB Pharmaceuticals, Teva Neurosciences, Novartis, Glaxo-Smith-Kline, and Boehringer Ingelheim.Dr. Pfeiffer has received personal compensation in an editorial capacity for Parkinsonism and Related Disorders.Dr. Pfeiffer has received (royalty or license fee or contractual rights) payments from Butterworth Heinemann, Elsevier, CRC Press, Taylor & Francis, and Humana Press.Dr. Pfeiffer has received research support from Boehringer Ingelheim, UCB Pharmaceuticals, and Schwarz Biosciences. Dr. Marsh has received research support from Eli Lilly & Company, Forest Pharmaceuticals, Acadia, Ovation, and National Institutes of Health. Dr. Hiner has received personal compensation for activities with Teva Neuroscience. Dr. Siderowf has received personal compensation for activities with Teva Neuroscience, Supernus Pharmaceuticals, Schering-Plough, and Merck Serono. Dr. Siderowf has received research support from the NINDS, the Department of Health of the Commonwealth of Pennsylvania, and Avid Radiopharmaceuticals. Dr. Payami has nothing to disclose. Dr. Molho has received personal compensation for activities with Allergan, Teva, Merz, Ipsen, and Boehringer Ingelheim. Dr. Molho has received research support from Teva, Allergan, Merz, IPsen, Parkinson9s Study Group, and Huntington9s Study Group. Dr. Nutt has received personal compensation for activities with XenPort, Impax Laboratories, Neurogen, Synosia, Neuroderm, Merck, Lily/Medtronic, Elan Pharmaceuticals, Lundbeck, Merz Pharmaceuticals, Synagile, and the National Parkinson Foundation. Dr. Nutt has received research support from Merck. Dr. Factor has received personal compensation for activities with Merz and Ipsen as a consultant. Dr. Factor has received personal compensation in an editorial capacity for Current Neurology and Neuroscience. Dr. Factor has received research support from Ceregene, Teva Neuroscience, Ipsen, and EMD Serono. Dr. Ottman has received personal compensation for activities with Ortho-McNeil Janssen Scientific Affairs, LLC. Dr. Clark has nothing to disclose. Dr. Marder has received personal compensation in an editorial capacity for Current Neuroscience. Dr. Marder has received research support from the NIH, Michael J. Fox Parkinson Disease Foundation, CHDI, and the Huntington9s Disease Society of America.