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Authors define clinical and radiological characteristics of an inherited encephalopathy by sharing data of three families.

Pt.1 (boy) underwent multiple episodes of encephalopathy with seizures and one episode of hepatic insufficiency from age 2mo to 2.5y, all related to viral infections. His maternal half-brother had one similar, infection-related neurologic event at age 7y.  Both had high CSF-protein level and symmetric, partially haemorrhagic lesions involving the deep gray matter, mamillary bodies, brainstem and cerebral white matter.

A girl (pt.2) had febrile encephalopathic episodes with elevated CSF-protein, haemorrhagic bithalamic and brainstem laesions at 1 and 2y of age. Her father had influenza-related encephalopathy with elevated CSF protein at age 8 y. His mother might have undergone a similar episode during infancy.

Another girl (pt.3) had two viral disease-related encephalopathic episodes with high CSF-protein and symmetric haemorrhagic lesions involving the deep gray matter and brainstem at 5 and 8 y of age. A paternal uncle died of febrile encephalopathy at age 6 y.

In view of the visibly autosomal dominant inheritance RANBP2 gene was sequenced and pathogenic variants were found in all the patients, the brother and mother of pt.1, the father and grandmother of pt.2 and the father of pt.3. Genetic testing of a 4^th family is in progress.

Conclusion: Symmetric, haemorrhagic deep gray matter and brainstem lesions of a patient with infection-related encephalopathy and elevated CSF-protein is typical of acute necrotizing encephalopathy. A dominantly inherited form is caused by RANBP2 mutations. It is suspected in all familial and/or recurrent cases.

autosomal dominant acute necrotizing encephalopathy; RANBP2 gene; recurrent encephalopathic episodes