A Systematic Review of Genetic, Clinical, and Gender Associated Aspects of the SNCA Gene in Familial Parkinson’s Disease

Abstract

Parkinson's disease (PD) presents as a progressive neurological disorder that manifests through motor symptoms such as tremors and movement stiffness, which drastically affect both mobility and quality of life. This is caused by dopamine-producing cells in the brain. The worldwide prevalence is estimated at 149 cases per 100,000 persons, indicating a rise to 25.2 million by 2050. By conducting a comprehensive PubMed database search for SNCA AND Parkinson's from 2020 to 2025, with adult populations as the focus, the researchers identified relevant studies for data extraction and analysis. The SNCA gene holds critical significance because it produces alpha-synuclein, which forms toxic Lewy bodies in brain tissue. Rare SNCA mutations that result in gene multiplication trigger severe early-onset Parkinson's disease, while common genetic variations such as REP1 polymorphism increase idiopathic PD risk. Research indicates that individuals with longer SNCA-Rep1 alleles have a greater chance of developing Parkinson's disease while also experiencing worsening cognitive impairment and non-motor symptom severity. Men exhibit a 1.5-2 fold higher prevalence of Parkinson's disease and experience symptoms earlier in life compared to women, but women display tremors more frequently when diagnosed with the disease. Female patients show elevated striatal dopamine measurements while experiencing symptoms and describe a greater intensity of pain and emotional responses. The evaluation of motor symptoms like bradykinesia through gyroscope signals demonstrates potential since it aligns closely with clinical rating scales such as the Unified Parkinson's disease rating scale (UPDRS). Many non-motor symptoms, including neuropsychiatric difficulties, sleep disorders, and autonomic dysfunction, affect up to 95% of patients with hyposmia and lower quality of life before motor symptoms appear. Analysing how genetics and gender contribute to symptom development is crucial for developing improved diagnostic tools and treatment methods for Parkinson's disease.