Clinical and Genetic Characteristics of Patients with Essential Tremor Who Develop Parkinson’s Disease

TL;DR

This study examines patients with essential tremor who later develop Parkinson’s disease to better understand the genetic and clinical connections between the two conditions.

Contribution

The study identifies novel genetic variants in patients with overlapping essential tremor and Parkinson’s disease features.

Findings

Seventeen different mutations were detected in 16 out of 40 patients with ET who later developed PD.

Three pathogenic or likely pathogenic variants were identified, none previously linked to PD following ET.

The findings suggest a need for further research into the genetic basis of overlapping ET and PD features.

Abstract

Background and Objectives: Essential tremor (ET) is a common neurological disorder, typically presenting as bilateral, rhythmic, and symmetric kinetic or postural tremors. In contrast, Parkinson’s disease (PD) is a progressive neurodegenerative disorder, characterized by resting tremor, rigidity, bradykinesia, and postural instability. Although both disorders involve tremor, ET and PD differ in clinical presentation and pathophysiology: ET generally involves action tremor and has a strong familial component, while PD more commonly presents with resting tremor and a weaker family history. A subset of ET patients may develop Parkinsonian features over time, although the relationship between ET and subsequent PD remains unclear. Genetic studies have identified only a few pathogenic variants in ET, suggesting it develops as a result of multifactorial genetic and environmental influences rather than simple Mendelian inheritance. ET is also recognized as a risk factor for developing PD, although the underlying mechanisms remain poorly understood. This study aimed to clarify potential genetic overlaps and distinctions in patients diagnosed with both ET and PD. Materials and Methods: We retrospectively analyzed 40 patients with a family history of ET or PD who were initially diagnosed with ET and later developed PD. Genetic screening and clinical assessments were conducted to investigate associated variants and clinical features. Results: Among these 40 patients, 17 different mutations were detected in 16 individuals. Three pathogenic or likely pathogenic variants were identified. The clinical characteristics and treatment responses of these patients were reviewed in relation to their genetic findings. Notably, none of the identified variants had previously been reported in association with PD following ET. Conclusions: A comprehensive clinical and genetic evaluation of ET patients who develop PD may offer insights into the underlying pathophysiology and inform future therapeutic strategies. Our findings support the need for further studies to explore the genetic landscape of patients with overlapping ET and PD features.

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