Clinical Characteristics of Parkinsonism in Frontotemporal Dementia Syndromes Associated with Mutations in MAPT, PGRN, C9ORF72 (P06.075)

Abstract

Objective: To compare and contrast the features of parkinsonism in cases with different genetic mutations associated with frontotemporal lobar degeneration (FTLD). Background FTLD has been associated with mutations in the microtubule associated protein tau ( MAPT) , progranulin (PGRN) and the GGGGCC hexanucleotide repeat expansion in the open reading frame 72 on chromosome 9 ( C9ORF72 ). Several of affected individuals with an FTLD syndrome exhibited parkinsonism. The specific features of parkinsonism associated with these mutations have not been well-characterized. Design/Methods: Using data collected prospectively on the UPDRS during the course of yearly visits, we analyzed all the parkinsonian features of the patients affected by one of the three mutations. Results: We compared 14 cases with C90RF72 , 12 with PGRN and 12 with MAPT that had parkinsonism. A symmetric akinetic-rigid parkinsonism phenotype was present in the majority of the cases. Hypomimia and bradykinesia were the most common features. Tremor was present in 5% of the cases with C90RF72 , 18% with MAPT , and absent in all cases with PGRN . None in whom levodopa therapy was administered benefited from treatment. Conclusions: Although some variability exists, among those with familial FTLD associated with mutations in C90RF72, PGRN and MAPT mutations, the parkinsonian features are typically akinetic rigid and symmetric without a significant presence of tremor. Supported by: Grants AG016574, AG006786, the ALS Association, and the Robert H. and Clarice Smith and Abigail Van Buren Alzheimer s Disease Research Program of the Mayo Foundation. Disclosure: Dr. Savica has nothing to disclose. Dr. Graff-Radford has received personal compensation for activities with Codman as a participant on a scientific advisory board. Dr. Graff-Radford has received personal compensation in an editorial capacity for the Neurologist. Dr. Graff-Radford has received research support from Janssen Pharmaceuticals, Inc., Pfizer Inc, Medivation, Inc., Forrest Laboratories and Allon Therapeutics Inc. Dr. DeJesus-Hernandez has nothing to disclose. Dr. Knopman has received personal compensation for activities with Lilly Pharmaceuticals as a data safety monitoring board member. Dr. Knopman has received personal compensation in an editorial capacity for Neurology. Dr. Knopman has received research support from Elan, Forest, and Baxter. Dr. Adeli has nothing to disclose. Dr. Boot has nothing to disclose. Dr. Kuntz has received research support from Cephalon, Inc. Dr. Petersen has received personal compensation for activities with Pfizer, Inc., Janssen Alzheimer9s Immunotherapy, Elan Pharmaceuticals, and GE Healthcare. Dr. Rutherford has nothing to disclose. Dr. Baker has nothing to disclose. Dr. Rademakers has nothing to disclose. Dr. Boeve has nothing to disclose.