Progressive cavitating leukoencephalopathy associated with a homozygous POLG mutation of 264C>G (p.F88L)

Progressive cavitating leukoencephalopathy is a childhood neurodegenerative syndrome characterized by brain MR imaging findings of patchy leukoencephalopathy with cavities and vascular permeability, initially affecting the corpus callosum and centrum semiovale, and eventually coalescing into large cystic regions of white matter. We report a case of progressive cavitating leukoencephalopathy in a 2-year-old female patient presenting as intermittent motor deficits which partially resolved over several months. Whole exome sequencing revealed a homozygous c.264C>G (p.F88L) POLG variant of uncertain pathogenicity which was potentially related to this presentation. Further testing and information are needed to prove the pathogenicity of this variant, but considering other studies which report similar genotypes in association with differing phenotypes, the current case report supports a possible pathogenicity. This case could therefore represent the first reported instance of progressive cavitating leukoencephalopathy in the presence of a POLG mutation.