Purpose or Case Report: To familiarize the pediatric radiologist with the important role that the perforin gene plays in lymphocyte cytotoxicity, to discuss the diversity in clinical presentation, and review the scope of neuroimaging abnormalities that may arise in the setting of a missense perforin genetic defect. The brain MRI findings and relevant clinical information of two remotely related children with the same novel missense mutation in the perforin gene represent the basis of this educational poster.

Perforin is a glycoprotein (encoded by the PRF-1 gene) involved in several human cellular functions, including, immune response and stored mainly in CD8-positive T-cells as well as natural killer (NK) cells. Normally, T-cells and NK cells are responsible for attacking dead cells. In the clinical setting of perforin deficiency, T-cells and NK cells attack the healthy immune system. This arises from a missense mutation of the PRF-1 gene. Links between perforin deficiency and the autoimmune clinical syndrome of hemophagocytic lymphohistiocytosis (HLH), have been reported.

MR imaging abnormalities in patients with perforin gene mutations, are diverse and complex as the defect may occur in the setting of familial hemophagocytic lymphohistiocytosis, primary necrotizing lymphocytic CNS vasculitis or associated with CNS infections such as the Epstein Barr virus.

To date, MRI abnormalities that have been reported include mimics of septic cerebral emboli, confluent white matter abnormalities involving the cerebral hemispheres and cerebellum invoking the consideration of diffuse demyelinating disease, and multifocal infratentorial and supratentorial intraaxial lesions with “necrotic-like” character and marginal enhancement. Multifocal sites of perivascular space pathological enhancement has also been reported. Common to many of these reports is cerebellar involvement.

The imaging differential diagnosis includes atypical infection, histocytic disorders of the CNS, lymphomatous granulomatosis, neurosarcoidosis, and primary CNS lymphoma.
Methods & Materials:
Results:
Conclusions: