Atypical clinical course in two patients with GNB1 variants who developed acute encephalopathy.

INTRODUCTION:Variants in the GNB1 gene, which encodes the β1 subunit of a trimeric G protein, can cause moderate to severe psychomotor retardation. Acute encephalopathies have also been observed in patients with central nervous system abnormalities; however, severe neurological sequelae have not previously been reported. CASE PRESENTATIONS:Patient 1 was a Japanese female with a de novo GNB1 variant (c.284 T > C). At 8 months old she contracted influenza A and developed generalized convulsions. In the acute phase, brain magnetic resonance imaging (MRI) findings indicated acute encephalopathy; diffuse cerebral atrophy was present 1 month later. Although multidisciplinary treatment was administered, she had severe neurological sequelae including spastic tetraplegia, severe intellectual disabilities, and refractory epilepsy. Patient 2 was a Japanese male with a de novo GNB1 variant (c.239 T > C). He experienced an unexplained respiratory arrest aged 17 years; refractory convulsions developed. Brain MRI at 1 month showed bilateral basal ganglia high intensities; at 3 months, diffuse cerebral cortex and white matter atrophy was observed. Despite multidisciplinary treatment, he developed severe spastic tetraplegia and mental regression. DISCUSSION:We report two patients with GNB1 variants who had acute lesions on brain MRI and unexpected disease courses. In such patients with acute neurological deterioration, multidisciplinary treatment is required; patients should also be carefully observed for progression to acute encephalopathy.