Abstract

Objective: The alpha-synuclein gene (SNCA) is implicated in both Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). The purpose of this case study was to describe the neuropsychological profile, clinical trajectory, and treatment course of an individual with a known SNCA gene duplication who was followed over the course of three years. Methods: The patient was a healthy man who developed olfactory changes in early adulthood followed by parkinsonism and cognitive concerns around age 40. He underwent serial neurologic and neuropsychological evaluations and neuroimaging, as well as genetic testing for PD gene mutations. He consented to share his medical information to increase awareness of his condition. Results: Initial neuropsychological evaluation (age 44) revealed mild cognitive impairment primarily affecting executive and frontal/subcortical functions. Follow-up evaluations showed rapid cognitive decline that far surpassed the patient’s Parkinsonism, which responded well to carbidopa-levodopa. As symptoms progressed, he also developed features characteristic of DLB, including cognitive fluctuations, rapid eye movement sleep behavior disorder, and visual hallucinations. Conclusion: SNCA gene duplication has classically been associated with a slowly progressive syndrome closely resembling idiopathic PD, but less frequently it can cause rapidly progressive dementia. This case study is the first to describe this rare phenotype in terms of its full neuropsychological profile and trajectory. The case highlights the value of a transdisciplinary evaluation and treatment and brings up important ethical and practical issues that should be considered when working with patients who have suspected or known genetic disorders.

摘要

目的： α-突触核蛋白基因 ( SNCA ) 与帕金森氏病 (PD) 和路易体痴呆 (DLB) 相关。本案例研究的目的是描述一个已知SNCA基因重复的个体的神经心理学概况、临床轨迹和治疗过程，该个体被随访了三年。方法：患者是一名健康男性，在成年早期出现嗅觉变化，随后在 40 岁左右出现帕金森病和认知问题。他接受了一系列神经学和神经心理学评估和神经影像学检查，以及 PD 基因突变的基因检测。他同意分享他的医疗信息，以提高对他病情的认识。结果：最初的神经心理学评估（44 岁）显示轻度认知障碍主要影响执行和额叶/皮质下功能。后续评估显示认知能力迅速下降，远远超过患者的帕金森病，后者对卡比多巴-左旋多巴反应良好。随着症状的进展，他还出现了 DLB 的特征，包括认知波动、快速眼动睡眠行为障碍和幻视。结论： SNCA基因重复通常与非常类似于特发性 PD 的缓慢进展综合征相关，但较少见的是它可引起快速进展性痴呆。本案例研究首次根据其完整的神经心理学概况和轨迹来描述这种罕见的表型。该案例强调了跨学科评估和治疗的价值，并提出了在与疑似或已知遗传病患者打交道时应考虑的重要伦理和实践问题。