Abstract Details

Title SNCA G51D Missense Mutation Causing Juvenile Onset Parkinson’s Disease

Topic Movement Disorders

Presentation(s) P5 - Poster Session 5 (5:30 PM-6:30 PM)

Poster/Presentation
Number 10-026

Objective To report the clinical and genetic features in a Parkinson’s patient with the SNCA G51D missense mutation.

Background α-synuclein (SNCA) gene mutations are recognized for causing rare familial forms of Parkinson’s disease (PD). The SNCA G51D missense mutation has been associated with a unique parkinsonian phenotype, often overlapping PD and multiple system atrophy, and with abundant pathological accumulation of α-synuclein. In the few published cases available, symptomatology of G51D patients reveals early onset, levodopa-responsive parkinsonism, pyramidal signs, cognitive impairment, visual hallucinations, and autonomic dysfunction.

Design/Methods A 23 year-old male of European ancestry with a 9-year history of parkinsonism first developed visual hallucinations at age 10 and tremors in his left leg and right arm at age 14. He developed profound motor parkinsonism with rapid progression, marked wearing off, dyskinesias, stiffness, and freezing (video). He is responsive to medications including carbidopa/levodopa, rotigotine, and apomorphine, but other PD-medications provided only short-term benefit. Visual hallucinations have been absent in his adulthood. Current neuropsychological evaluation reveals a MMSE 26/30 and intact cognitive function. DBS evaluation is presently underway. Of note, his father died at the age of 42 after having parkinsonism and dementia; autopsy revealed diffuse Lewy Body disease with severe involvement of hippocampal CA2-4 fields.

Results Using a next generation sequencing panel we screened the entire coding region and intron-exon boundaries of 18 genes linked to neurodegenerative disorders in which parkinsonism has been reported. We identified a pathogenic mutation in the SNCA gene, c.152G>A (p.Gly51Asp).

Conclusions This report illustrates a case of the SNCA G51D missense mutation causing parkinsonism with marked motor fluctuations, modest dopaminergic response, and intact cognitive/autonomic function. To our knowledge, our case is the youngest reported for age of onset. While cases in the literature share the G51D genotype, clinical phenotypes remain heterogeneous. Future reports on responsiveness to DBS will be informative regarding therapies/outcomes.

Authors/Disclosures
Christa S. Cooper, PA (Rush University Medical Center) PRESENTER	No disclosure on file
Jennifer G. Goldman, MD, MS, FAAN	Dr. Goldman has received personal compensation in the range of $500-$4,999 for serving as an officer or member of the Board of Directors for Parkinson's Foundation Scientific Advisory Board. The institution of Dr. Goldman has received research support from Michael J. Fox Foundation. The institution of Dr. Goldman has received research support from Parkinson's Foundation.
Cyrus P. Zabetian, MD (VA Puget Sound Health Care System)	The institution of Dr. Zabetian has received research support from American Parkinson Disease Association. The institution of Dr. Zabetian has received research support from Department of Veterans Affairs. The institution of Dr. Zabetian has received research support from NIH. Dr. Zabetian has a non-compensated relationship as a Member, Scientific Advisory Council with Lewy Body Dementia Association that is relevant to AAN interests or activities.
	No disclosure on file
James B. Leverenz, MD, FAAN (Cleveland Clinic)	Dr. Leverenz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acadia. Dr. Leverenz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Leverenz has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eisai.

��ɫ��

��ɫ��