Biallelic PRKN (Parkin) mutations are associated with autosomal recessive early-onset Parkinson’s disease (PD), typically marked by slow progression and a good response to dopaminergic therapy. However, it may also show atypical features such as dystonia and tremors that may resemble Essential Tremor (ET). The precise role of PRKN mutations in the coexistence of ET and PD is not fully understood.

A 44-year-old woman with a history of learning disability and anxiety presented with progressive action tremor beginning in adolescence. Her family history included tremor in her father, paternal grandfather, sister, and son. The tremor, initially in her hands, spread to her legs, voice, trunk, and head, becoming disabling by her 30s. Neurologic examination showed severe high-amplitude tremor in her upper extremities, legs, neck, and voice, leading to a diagnosis of ET. Multiple medications, including levodopa, failed to provide significant benefit, though alcohol and cannabis provided partial relief. At age 39, she underwent a gamma knife thalamotomy of the ventral-intermediate nucleus (VIM) of the thalamus, which was unsuccessful. In her early 40s, she developed bilateral foot dystonia. Genetic testing identified 2 pathogenic biallelic PRKN variants; no mutations associated with ET were found. DaT-SPECT showed decreased dopamine transporter availability, and she was subsequently diagnosed with PD. Levodopa was resumed with partial improvement, but due to an unsatisfactory response to medication, she is now being evaluated for deep brain stimulation (DBS).

This case underscores the importance of genetic testing in ET, especially for patients with a strong family history. Earlier identification of the PRKN mutation could have optimized management, potentially avoiding gamma knife surgery in favor of DBS. Research indicates that patients with PRKN mutations may respond well to DBS, which may better address bradykinesia and tremor. Personalized treatment plans should integrate genetic testing and early intervention for optimal outcomes.