Variable Presentation and Reduced Penetrance in Autosomal Dominant Acute Necrotizing Encephalopathy Related to RANBP2...

Area of Science:

• Neurology
• Genetics
• Pediatrics

Background:

• Acute necrotizing encephalopathy (ANE) is a rare neurological disorder typically affecting children after viral infections.
• While most ANE cases are sporadic, autosomal dominant ANE (ADANE) is linked to a RANBP2 gene variant.
• ADANE presents with neurological symptoms, characteristic brain MRI findings, and rapid deterioration.

Observation:

• This study describes six members from two South American families with ADANE.
• Genetic sequencing identified a heterozygous c.1754C>T variant in the RANBP2 gene (p.Thr585Met) in affected and some asymptomatic individuals.
• The report details clinical manifestations, disease progression, and MRI findings in these families.

Findings:

• The study confirms the association of the RANBP2 variant with ADANE.
• It highlights incomplete penetrance, where some carriers of the variant do not exhibit symptoms.
• Significant intrafamilial phenotypic variability in disease severity and outcome was observed.

Implications:

• This research expands the understanding of ADANE genetics and clinical presentation.
• It underscores the importance of genetic counseling for families with a history of recurrent ANE.
• The findings contribute to the differential diagnosis of similar pediatric neurological conditions like Leigh disease.