Colony‐stimulating factor 1 receptor‐related disorder: Clinical variability of biallelic variants

CSF1R-related disorder (CSF1R-RD) is a rare inherited condition that affects the brain and, in some people, the bones. It is caused by changes in the CSF1R gene, which is important for the normal function of microglia, the brain's immune cells. Because the disease is rare and symptoms vary widely, diagnosis can be difficult. In this study, we describe six people from four unrelated families who had two altered copies of the CSF1R gene. Their symptoms ranged from severe childhood-onset neurological disease with loss of walking and speech to very mild disease, with one individual remaining symptom-free despite having brain MRI abnormalities. Some patients had skeletal abnormalities, while others had only neurological symptoms. These findings show that the severity of the disease cannot be predicted by the genetic variant alone and that other genetic, biological, or environmental factors are likely involved.