Broadening the clinical spectrum of White-Sutton syndrome, implications for co-morbidity with celiac disease in a patient with a novel likely pathogenic variant in the POGZ gene.

White-Sutton syndrome (WHSUS) is a rare neurodevelopmental disorder caused by heterozygous variants in the POGZ gene. With slightly over 100 reported cases, the diagnosis of WHSUS remains challenging due to its variable and non-specific clinical features. We report a novel case of WHSUS carrying a heterozygous de novo variant in the POGZ gene and with characteristic clinical features including global developmental delay, autism spectrum disorder, generalised myoclonic epilepsy, hypotonia and distinct dysmorphic features. Notably, the patient also presented with mild gastrointestinal symptoms and was diagnosed with celiac disease (CD) based on elevated tissue transglutaminase IgA levels, confirmatory duodenal biopsy and HLA typing. Based on the recent evidence implicating chromatin remodelling genes in CD and the known role of the POGZ protein as a regulator of chromatin remodelling, we cautiously propose, for the first time, to our knowledge that the POGZ gene may contribute to the pathogenesis of the celiac disease, providing evidence of a possible association between White-Sutton syndrome and CD. Comprehensive functional, genetic and epidemiological studies are needed to explore further this potential association, which may broaden the clinical spectrum of WHSUS and improve the understanding of CD-related epigenetic factors.