Clinical, radiological and possible pathological overlap of cystic leukoencephalopathy without megalencephaly and Aicardi-Goutières syndrome

•There is a clinical and radiological overlap between RNASET2-related leukodystrophy and AGS in some cases.•RNASET2-related leukodystrophy and AGS should be considered in the same differential diagnosis.•Pathomechanisms related to auto-inflammation are possibly shared between RNASET2-related leukodystrophy and AGS.

BackgroundCystic leukoencephalopathy without megalencephaly is a disorder related in some cases to RNASET2 mutations and characterized by bilateral anterior temporal subcortical cysts and multifocal lobar white matter lesions with sparing of central white matter structures. This phenotype significantly overlaps with the sequelae of in utero cytomegalovirus (CMV) infection, including the presence of intracranial calcification in some cases. Aicardi-Goutières syndrome (AGS) is another inherited leukodystrophy with cerebral calcification mimicking congenital infection. Clinical, radiological and biochemical criteria for the diagnosis of AGS have been established, although the breadth of phenotype associated with mutations in the AGS-related genes is much greater than previously envisaged.Patients and MethodsWe describe the clinical, biochemical and radiological findings of five patients demonstrating a phenotype reminiscent of AGS.ResultsAll patients were found to carry biallelic mutations of RNASET2.ConclusionsOur patients illustrate the clinical and radiological overlap that can be seen between RNASET2-related leukodystrophy and AGS in some cases. Our data highlight the need to include both disorders in the same differential diagnosis, and hint at possible shared pathomechanisms related to auto-inflammation which are worthy of further investigation.