Novel Postzygotic Variants Associated With Hypomelanosis of Ito Expand the ACTB-Related Neurocutaneous Disease...

Several clinical entities are associated with ACTB pathogenic variants. Most notably, constitutional missense gain-of-function variants are linked to Baraitser-Winter cerebrofrontofacial syndrome, and recurrent somatic gain-of-function Arg147 variants are reported in Becker's nevus or in smooth muscle hamartomas. We describe three individuals with mosaic hypopigmentation following Blaschko's lines, associated or not with neurodevelopmental features, with postzygotic ACTB variants identified with deep next-generation sequencing on skin biopsy from an affected area. We identified the same missense p.(Arg335His) variant in individuals #1 and #3, already reported in a constitutional state in a fetus. Individual #2 carried an unreported in-frame insertion-deletion (p.(Ser348_Leu349insPheHisLeuProProSerIle)). Thus, we describe a previously unreported phenotype related to postzygotic ACTB variants with hypopigmentation associated or not with neurodevelopmental features, distinct from Becker presentations, bridging constitutional neurodevelopmental and somatic cutaneous phenotypes.