Variable clinical course in acute necrotizing encephalopathy and identification of a novel RANBP2 mutation

Acute necrotizing encephalopathy (ANE) is a rare disease presenting with rapidly progressing encephalopathy. It usually occurs in otherwise healthy children after common viral infections. The hallmarks of ANE are the neuroradiological findings of multiple symmetric lesions in the thalami, midbrain, pons and brainstem. Most cases are sporadic and non recurrent. However, recurrent or familial forms of ANE due to mutations in RANBP2 gene have been reported. It has been suggested to give these cases the term ANE1. We report the clinical course in two male infants (P1, P2) with ANE1 and a variable clinical course and outcome. One patient is heterozygous for the most common RANBP2 missense mutation p.Thr585Met. In the other patient we observed a novel de novo missense mutation p.Trp681Cys in the RANBP2 gene causing recurrent ANE. Clinical and radiological features are presented and differential diagnoses are discussed. This report adds to the current knowledge of the phenotype in ANE, caused by mutations in RANBP2 gene.