White-Sutton syndrome (WHSUS) is a rare neurodevelopmental disorder due to pathogenic variants in the POGZ gene. Its phenotype includes developmental delay, behavioral dysfunctions, hypotonia, and dysmorphic features. The condition is still poorly known: comprehensive clinical descriptions and exhaustive genotype-phenotype correlations are lacking, limiting diagnostic and therapeutic advancements. Here, we report molecular, clinical, and instrumental data from the first and largest Italian cohort (19 patients). Our results highlight the importance of an extensive approach at the time of diagnosis-including early nutritional support for preventing obesity-related complications and instrumental screening for congenital malformations. Preliminary data suggest that splicing variants could be associated with more severe phenotypes. This study provides valuable new insights into WHSUS and represents a significant step towards its comprehension.
