Genetic Mutations and Deep Brain Stimulation

Parkinson disease (PD) is a neurodegenerative disorder characterized by rest tremor, rigidity, bradykinesia, and postural instability. While most cases of PD are sporadic in nature, cases secondary to genetic mutations have been identified. These are typically monogenic and often present as early-onset or juvenile-onset PD. While rare, individuals with PD may harbor multiple pathogenic variants in PD-linked genes, potentially leading to more severe presentations. This chapter reviews available data regarding deep brain stimulation (DBS) targets and DBS outcomes in cases that are genetically proved to be PD. We report a patient with juvenile-onset PD whose course featured severe peak-dose dyskinesias and generalized off dystonias. Genetic testing supported a rare diagnosis of digenic PD, with homogenous deletions in PRKN (Parkin) and a single transition in PARK6 (PINK1). Bilateral DBS electrodes were implanted into the globus pallidus pars interna (GPi), leading to significant amelioration of both off and on symptoms.