Highlighting the CSF1R mutational spectrum: c.2549C>T variant in late-onset leukoencephalopathy mimicking multiple...

Late-onset CSF1R-related disorder is an ultra-rare neurogenetic disorder caused by pathogenic variants in the colony-stimulating factor 1 receptor (CSF1R) gene. Due to the rapid disease progression and rapid deterioration of neuropsychological status of affected individuals, prompt and accurate diagnosis is essential. This report aims to highlight the need for clinicians to consider this differential diagnosis in patients with a rapidly progressive clinical course of multiple sclerosis (MS).

We report the case of an adult male presenting with rapidly progressive neurological deficits initially attributed to MS. Serial neuroimaging demonstrated progressive enlargement of hyperintense white matter lesions, correlating with marked clinical deterioration despite ongoing treatment. Genetic evaluation performed because of the aggressive disease course revealed a previously reported in a single patient variant in the CSF1R gene (c.2549C > T; p.Ser850Leu), located within the critical tyrosine kinase domain (TKD) of the receptor. In silico analysis, together with the patient's clinical phenotype, supported classification of this variant as likely pathogenic.

This case underscores the importance of considering CSF1R-related disorder not only in the differential diagnosis of adult-onset leukoencephalopathies but also in patients with rapidly progressive MS-like disease. Identification and characterization of novel variants contribute to expanding genotype-phenotype correlations in late-onset CSF1R-related disorder and highlight the crucial role of genetic testing in atypical MS cases.