Phenotypic variability in RERE-related disorders and the first report of an inherited variant.

ABSTRACT

RERE-related disorders, also known as Neurodevelopmental Disorders with or without Anomalies of the Brain, Eye, or Heart (NEDBEH), are caused by heterozygous pathogenic variants in the arginine-glutamic acid dipeptide repeats gene (RERE). Up-to-date, 20 cases have been reported with the core characteristics of developmental delay, intellectual disability, and/or autism spectrum disorder. Here, we describe three additional cases. In the first case, the patient was found to have a previously reported de novo missense variant; her clinical findings of global developmental delay, intellectual disability, autism spectrum disorder, vision abnormalities, musculoskeletal anomalies, dysmorphic facial features, and a congenital heart defect strengthen existing genotype-phenotype correlations. We also describe the first inherited variant in RERE, found in a patient (case 2) with developmental delay, autism, and hyperopia and his mother (case 3) with ADHD, myopia, and history of mild speech delay. Lastly, by summarizing the clinical features presented in the 23 cases now reported, we provide an updated review of the literature.