Isolated Sixth Nerve Palsies in a Child With Familial Hemophagocytic Lymphohistiocytosis Type 2

A previously healthy 2-year-old boy presented with a left sixth cranial nerve palsy. There was a family history of multiple sclerosis and optic neuritis. Neuroimaging showed multiple foci of T2/FLAIR hyperintense signal abnormality in both cerebral hemispheres and in the brainstem. The initial diagnosis was suspicious for demyelinating disease. However, there was no clinical improvement after a course of corticosteroids, and there was no change in his follow-up MRI. He later developed bilateral sixth nerve palsies, with esotropia addressed with bilateral medial rectus botulinum toxin injections. A brain biopsy was planned. However, his 3-month-old sister was separately admitted for fever and pancytopenia. She had markedly elevated ferritin, D-dimer, triglycerides, sIL-2R, CXCL9, and IL-18 and low fibrinogen. Her bone marrow biopsy showed hemophagocytosis. Genetic testing of both siblings revealed biallelic mutations in the PRF1 locus. The final diagnosis of familial hemophagocytic lymphohistiocytosis Type 2 was made. Both siblings underwent chemotherapy. The boy's sixth nerve palsies and MRI abnormalities resolved. Both siblings then went on to undergo bone marrow transplant.