CSF1R-related disorder: A clinical, imaging and genetic profile review.

Background: Colony-stimulating factor 1 receptor (CSF1R) -related disorder (CSF1R-RD) is a primary microgliopathy with a distinct clinical, imaging and genetic profile.

Objective: Description of the clinical, imaging and genetic profile of CSF1R-RD and comparison of Indian cohort with Asian, European and American cohort.

Methods: Report of 2 cases of CSF1R-RD and review of reported cases of genetically confirmed CSF1R-RD since 2012 from Indian, Asian, European and American cohorts.

Results: Two patients were females with age at onset at 40 and 42 years. The duration of symptoms was 2 and 5 years. Both had spasticity, cognitive impairment and psychiatric disturbances. Brain imaging showed hyperintensities in the cerebral white mater involving deep and periventricular white mater with diffusion restriction in one patient. There was diffuse cerebral and corpus callosum atrophy. Genetics showed heterozygous missense variants in exon 18 of the CSF1R gene in both patients. The Indian cohort of 5 patients had additional symptoms of dysarthria, dysphagia, parkinsonism, tremor and gait abnormality, similar radiological features. The Asian, European and American cohort had similar clinical and radiological features. Seizures were more commonly reported in America cohort and presence of calcification was less common imaging abnormality in all cohorts. Genetic profiling showed heterozygous predominantly missense variants in the TKD in all cohorts.

Conclusions: CSF1R-RD has distinct clinical profile of cognitive impairment, spasticity, psychiatric disturbances with dysarthria, dysphagia, parkinsonism, tremor, ataxia, seizures, aphasia and gait abnormality. Calcification is less common radiological abnormality with heterozygous missense variants in the TKD as the common genetic variant.