Renpenning syndrome related to a missense variant in polyglutamine-binding protein 1 (PQBP1): Two pediatric cases from a Chinese family and literature review

Renpenning syndrome is a rare X-linked intellectual disability (XLID) caused by mutations in the polyglutamine-binding protein 1 (PQBP1) gene. Current understanding of its clinical features and pathogenesis remains limited, especially neuropsychological profile have not been fully investigated. We report a pair of Chinese siblings with Renpenning syndrome carrying a missense variant of PQBP1. They presented with severe intellectual deficiency, microcephaly, characteristic facial dysmorphism, short statures and lean body build. Neuropsychological assessment showed overall delayed development. Brain MRI scans indicated demyelination in which one patient exhibited improvement over a 6-year period. Both siblings experienced recurrent febrile convulsions before 5 years old, however, a diagnosis of epilepsy was not established. Notably, one child presented with multiple episodes of Henoch-Schönlein purpura (HSP), which has not been reported previously. Whole-exome sequencing identified a novel variant: C.28C > G (p.R10G) inherited maternally. Consequently, we report the first known Chinese cases of Renpenning syndrome, caused by a novel variant in PQBP1 gene. Our study has expanded the spectrum of PQBP1 variants and existing understanding of the neuropsychological phenotype.