Objective: To illustrate the case of a 60 years old woman with A53T point mutation derived Parkinson’s disease (PD) and to review SNCA mutations phenotype, focusing on non-motor features.

Background: Monogenic forms of PD have always been an intriguing field on which to search for PD pathophysiology. The first mutation associated with familial PD was found in SNCA gene in 1997. Since then, intensive research efforts have established a total of 16 genes and 20 loci containing causal mutations for parkinsonism clinically resembling PD.

Methods: A literature search was performed using the terms “SNCA”, “Parkinson’s disease”, “PD”, “α-synuclein mutations”, “α-synuclein”, “monogenic”, “duplication”, “triplication” and “point mutations”. All works lacking of accurate clinical data were discarded.

Results: 128 cases with SNCA related-PD were found in English literature. According to Kasten, cases were organized into three groups: point mutations (PM), duplication (DM) and triplication (TM). No difference was noted for gender. Average age at onset was 45.47 years. Patients with TM showed an early onset (36.96 ± 7.70 years), regarding patients with both DM (46.59 ± 11.43 years) and PM (47.56 ± 12.86 years). Regarding motor symptoms, 33% of all patients presented tremor at rest with the highest frequency (84%) in triplication group. The frequency of cognitive impairment was 25% in PM, 42.86% in DM and 68% in TM. Psychosis and postural hypotension were more frequently observed in TM. Hyposmia was more common in DM.

Conclusions: Despite being perceived as a pure movement disorder, PD finds in non-motor features a clinical and quality of life im-pacting factor. Our case, a novel A53T SNCA mutation, presented a wide range of non-motor features including postural hypotension, severe Rem Behavior Disorders (RBD) and hyposmia. The intriguing view of RBD as first indication of an impending α-synuclein disorder, was confirmed by the high frequency among SNCA mutation carriers, especially DM. Hyposmia might represent, as highlighted in our case, an early and severe presenting feature of PD. The efforts in phenotype characterization might allow both to identify patients at particular risk for specific clinical features and to clarify pathogenic mechanisms leading to the development of useful biomarkers, curative therapies, and preventive measures.

« Back to 2016 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/clinical-phenotype-of-parkinsonian-patients-with-synuclein-mutation-our-case-report-and-review-of-the-literature/