Coloboma may be a shared feature in a spectrum of disorders caused by mutations in the WDR37‐PACS1‐PACS2 axis

We report a male adult with early infantile‐onset epilepsy, facial dysmorphism, and iridal and choroidal coloboma who had a de novo heterozygous mutation in PACS2 , that is, c.625G > A p.(Glu209Lys). This specific mutation was previously reported in a patient with PACS2 ‐related disorder (early infantile epileptic encephalopathy 66). De novo heterozygous mutations in WDR37 have been shown to cause a novel human disorder, neurooculocardiogenitourinary syndrome (NOCGUS syndrome) (OMIM #618652), characterized by intellectual disability, facial dysmorphism, and coloboma. According to large‐scale interactome data, WDR37 interacts most strongly, by far, with PACS1 and PACS2. Clinically, coloboma has been described as a feature in a WDR37 ‐related disorder and a PACS1 ‐related disorder (Schuurs‐Hoeijmakers syndrome), but not in a PACS2 ‐related disorder. Our review of the phenotypes of three human disorders caused by WDR37 , PACS1, and PACS2 mutations showed a significant overlap of epilepsy, intellectual disability, cerebellar atrophy, and facial features. The present observation of coloboma as a shared feature among these three disorders suggests that this group of genes may be involved in ocular development. We propose that dysregulation of the WDR37‐PACS1‐PACS2 axis results in a spectrum that is recognizable by intellectual disability, distinctive facial features, and coloboma.