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A rare intronic c.2654+1G>A mutation in CSF1R-microglial encephalopathy: a case report
HongYan Wu1, JingYu Shi2, XiaoShan Wang1
1Department of Neurology, Guizhou University of Traditional Chinese Medicine, Guiyang, China.
Objective:
We report a case of CSF1R-microglial encephalopathy associated with a rare intronic c.2654 + 1G>A mutation, featuring negative diffusion-weighted imaging (DWI) findings and a cerebrospinal fluid (CSF) biomarker profile indicative of Alzheimer's disease-related changes, and we explore the associations between genetic mutations, CSF biomarker alterations, and neuroimaging manifestations.
Methods:
This study documents the demographic data, detailed medical history, and clinical manifestations of a patient with CSF1R-microglial encephalopathy. The medical histories of some family members were collected, and the proband underwent whole-exome sequencing (WES) for diagnostic confirmation.
Results:
The patient, a 53-year-old woman, presented with early-onset cognitive decline, personality changes, and behavioral abnormalities. Neuropsychological testing revealed severe cognitive impairment, and the CSF biomarker profile suggested Alzheimer's disease-related changes. Cranial MRI showed bilateral, symmetric deep white matter changes, brain atrophy (including corpus callosum thinning), and low signal intensity on DWI. Family history revealed that 3 out of 19 individuals across four generations, including the proband, her aunt, and her sister, developed dementia and progressed to severe cognitive impairment rapidly. WES analysis revealed a heterozygous c.2654 + 1G>A variant in the CSF1R gene (NM_005211.3), confirming a diagnosis of CSF1R-microglial encephalopathy caused by a dominant autosomal mutation in exon 20 of the CSF1R gene.
Conclusion:
CSF1R-microglial encephalopathy is a progressive disorder with diverse early clinical presentations, making it prone to misdiagnosis and delayed treatment. This case suggests that, contrary to previous findings, negative DWI results should not exclude CSF1R-microglial encephalopathy. In addition, CSF biomarker profiles in patients with CSF1R-microglial encephalopathy may exhibit Alzheimer's disease-related changes. Early genetic testing is critical, and for genetically linked diseases, testing other family members can help ensure early diagnosis and intervention.
Insights
This study details a rare CSF1R-microglial encephalopathy case with a specific mutation. Negative diffusion-weighted imaging (DWI) and Alzheimer's-like CSF biomarkers highlight the need for early genetic testing in cognitive decline cases.
Area of Science:
- Neuroscience
- Genetics
- Neurology
Background:
- CSF1R-microglial encephalopathy is a rare, progressive neurodegenerative disorder.
- Early diagnosis is often challenging due to diverse clinical presentations and potential misdiagnosis.
- Genetic mutations in the colony-stimulating factor 1 receptor (CSF1R) gene are implicated.
Observation:
- A 53-year-old woman presented with early-onset cognitive decline, personality changes, and behavioral abnormalities.
- Neuroimaging revealed white matter changes, brain atrophy, and negative diffusion-weighted imaging (DWI) findings.
- Cerebrospinal fluid (CSF) biomarkers suggested Alzheimer's disease-related changes.
Findings:
- Whole-exome sequencing (WES) identified a heterozygous c.2654 + 1G>A mutation in the CSF1R gene (NM_005211.3).
- This mutation confirmed a diagnosis of autosomal dominant CSF1R-microglial encephalopathy.
- The patient's family history revealed a high prevalence of rapidly progressing dementia across generations.
Implications:
- Negative DWI findings should not rule out CSF1R-microglial encephalopathy.
- CSF biomarker profiles can mimic Alzheimer's disease, underscoring the importance of genetic analysis.
- Early genetic testing and family member screening are crucial for timely diagnosis and intervention in hereditary neurological disorders.
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