Familial young-onset Parkinson's disease associated with SNCA gene duplication: a case series of three sisters from Turkey.

Abstract

SNCA gene duplications are a rare cause of autosomal dominant Parkinson's disease (PD), linked to early onset and cognitive or behavioral symptoms. Data from Turkey remain limited. To describe the clinical, cognitive, behavioral, and genetic features of three Turkish sisters with familial PD due to SNCA duplication. This retrospective case series includes three sisters with PD. Clinical history, neurological examinations, Unified Parkinson's Disease Rating Scale (UPDRS-III) scores, treatment history, and neuropsychological findings were recorded. Genetic testing was conducted using whole exome sequencing. One sister underwent subthalamic nucleus deep brain stimulation (STN-DBS), and outcomes were followed over time. All patients presented with early-onset PD and classic motor symptoms, including bradykinesia and rigidity. Non-motor features such as REM sleep behavior disorder, orthostatic hypotension, urinary incontinence, and hallucinations were common. Two developed impulse control disorders, including hypersexuality and compulsive behaviors. Cognitive decline occurred in two, with MoCA scores of 24 and 22, and neuropsychological testing revealed frontal and temporolimbic dysfunction. The sister treated with DBS showed initial improvement but later motor and cognitive progression. This first detailed Turkish familial series highlights the broad symptom spectrum of SNCA duplication PD and underscores the need for genetic and neuropsychiatric assessment in familial cases.