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.

Method: Our case is a 23 year-old male of European ancestry with a 9-year history of parkinsonism. He first developed visual hallucinations at age 10, followed by behavioral changes at age 12, and tremors in his left leg and right arm at age 14. He developed profound motor parkinsonism with rapid progression and marked wearing off, dyskinesias, stiffness, and freezing (video). He is responsive to medications including carbidopa/levodopa, rotigotine, and apomorphine, but multiple 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 for about 5 years; 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).

Conclusion: This report illustrates a case of the SNCA G51D missense mutation causing parkinsonism with marked motor fluctuations, modest dopaminergic response, and intact cognitive and 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 and outcomes.

« Back to 2019 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/snca-g51d-missense-mutation-causing-juvenile-onset-parkinsons-disease/