Motor and Nonmotor Features of Carriers of the p.A53T Alpha-Synuclein Mutation: A Longitudinal Study

• Published in: Movement disorders Vol. 31; no. 8; pp. 1226 - 1230
• Main Authors: Papadimitriou, Dimitra, Antonelou, Roubina, Miligkos, Michael, Maniati, Matina, Papagiannakis, Nikolaos, Bostantjopoulou, Sevasti, Leonardos, Athannassios, Koros, Christos, Simitsi, Athina, Papageorgiou, Sokratis G., Kapaki, Elisabeth, Alcalay, Roy N., Papadimitriou, Alexandros, Athanassiadou, Aglaia, Stamelou, Maria, Stefanis, Leonidas
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01-08-2016; Wiley Subscription Services, Inc
• Subjects: A53T; Adult; Aged; alpha-synuclein; alpha-Synuclein - genetics; asymptomatic; Autonomic nervous system; Autonomic Nervous System Diseases - etiology; Autonomic Nervous System Diseases - physiopathology; Clinical trials; Cognitive ability; Dementia - etiology; Dementia - physiopathology; Female; Heterozygote; Hormone replacement therapy; Humans; Longitudinal Studies; Male; Middle Aged; Motor task performance; Movement disorders; Mutation; Neurodegenerative diseases; Olfaction; Olfaction Disorders - etiology; Olfaction Disorders - physiopathology; Parkinson Disease - complications; Parkinson Disease - genetics; Parkinson Disease - physiopathology; Parkinson's disease; Penetrance; Psychotic Disorders - etiology; Psychotic Disorders - physiopathology; REM sleep; Sleep disorders; Synuclein; Parkinson's disease; A53T; alpha-synuclein; asymptomatic; penetrance
• ISSN: 0885-3185; 1531-8257
• DOI: 10.1002/mds.26615

ABSTRACT
Background
G209A SNCA mutation carriers represent an important group of genetic PD. We describe motor and nonmotor features of G209A SNCA mutation carriers.
Methods
Longitudinal clinical assessments over 2 years were collected in 22 symptomatic and 8 asymptomatic G209A SNCA mutation carriers. Motor and nonmotor rating scales were administered. Correlations were performed between clinical variables and disease duration or age. Penetrance was calculated using Kaplan‐Meier survival curves.
Results
Asymptomatic carriers did not manifest clear premotor symptoms, but symptomatic carriers often reported that olfactory dysfunction and rapid eye movement sleep behavior disorder preceded motor symptoms. Prominent motor decline and deterioration of autonomic and cognitive function occurred at follow‐up; such nonmotor features correlated with disease duration, but not age. Disease penetrance was estimated at around 90%.
Conclusions
This study may help to inform clinical trials and provide the basis for studies of disease modifiers in genetic synucleinopathy cohorts. © 2016 International Parkinson and Movement Disorder Society