A novel CSF1R mutation mimicking frontotemporal dementia: A glimpse into a microgliopathy

CSF1R-related leukoencephalopathy (CRL), formerly defined as adult-onset leukoencephalopathy with axonal spheroids and pigmented glia, hereditary diffuse leukoencephalopathy with spheroids, and pigmentary orthochromatic leukodystrophy (POLD), is a rare autosomal dominant leukoencephalopathy due to mutations in the CSF1R gene.1 This gene codes for the colony stimulating factor 1 receptor (CSF1R), a transmembrane tyrosine kinase receptor mainly expressed in microglia. The most accepted pathogenetic mechanism is CSF1R haploinsufficiency, causing a microgliopathy with primary axonopathy followed by demyelination.2 Characteristic pathological findings are reduced, dysmorphic and pigmented microglia, giant neuroaxonal swellings (spheroids) and blood-brain barrier (BBB) impairment. Patients typically show cognitive decline and neuropsychiatric symptoms, accompanied by motor signs.