Neuropathological Findings in a Case of Parkinsonism and Developmental Delay Associated with a Monoallelic Variant in PLXNA1.

BACKGROUND

PLXNA1 encodes for Plexin-A, a transmembrane protein expressed in the developing nervous system. Mutations in this gene have been associated with developmental delay but have not been previously associated with the development of parkinsonism.

OBJECTIVES

To describe the case of a 38-year-old patient with developmental delay who developed parkinsonism later in life.

METHODS

Post-mortem exome sequencing was performed with confirmation by Sanger sequencing. Brain autopsy was also performed.

RESULTS

Post-mortem exome sequencing on the proband identified a heterozygous predicted nonsense PLXNA1 variant (c.G3361T:p.Glu1121Ter). Pathology demonstrated arhinencephaly with brainstem heterotopia, diffuse Lewy body disease, and frontotemporal lobar dementia-tau.

CONCLUSIONS

This case of a patient with developmental delay and parkinsonism with PLXNA1 mutation highlights a need for assessing long-term outcomes of individuals with neurodevelopmental disorders, as well as the need for genetic testing in adults. It also suggests that the link between PLXNA1 and α-synuclein should be explored in the future. © 2021 International Parkinson and Movement Disorder Society.