Dementia associated with early‐onset Parkinson’s disease: Description of a family case in Colombia

Abstract

AbstractBackgroundParkinson’s Disease (PD) is a motor neurodegenerative disorder of the dopaminergic neurons in the substantia nigra1. One of the frequent complications is dementia and often is a late symptom1,2. Some studies suggest that around 10% of patients with PD develop dementia per year2,3. Mutations in PLA2G6 are responsible of PARK14, an autosomal recessive L‐DOPA responsive dystonia/parkinsonism with early/adult onset4. This phenotype presents a high clinical variability, which consists in the occurrence of cerebral and cerebellar atrophy, iron accumulation in the basal ganglia, and cognitive decline4. In this study, we describe the genotype of two brothers diagnosed with early onset PD and a phenotype with FTD‐like characteristics.MethodA complete clinical evaluation consisting of geriatric, psychyatric, neurologic and neurpsychologic evaluation, was carried out in two affected male individuals, and their family. NGS was performed (PD targeted panel, WES, WGS) and MLPA on the two affected individuals.ResultThe two affected individuals were diagnosed around their thirties, presenting classic motor symptoms of PD. Subsequently, dementia associated to frontotemporal disease was diagnosed. No iron accumulation in the basal ganglia was found in either of the affected siblings. Genetic tests showed the pathogenic variant in heterozygous state c.2132C>G, p.Pro711Arg in PLA2G6 gene in the two affected brothers and their healthy mother.ConclusionAtypical frontotemporal dementia in two siblings with early‐onset PD is described. Additional studies should be performed to identify another variant or another gene in this family. Some studies have risen the hypothesis that even heterozygous PLA2G6 mutations may cause PARK144.