Blepharophimosis–ptosis–epicanthus inversus syndrome (BPES) is an autosomal dominant disorder caused by mutations in FOXL2. We identified an individual with BPES and additional phenotypic features who did not have a FOXL2 mutation. We used whole exome sequencing to identify a de novo mutation in KAT6B (lysine acetyltransferase 6B) in this individual. The mutation was a 2‐bp insertion leading to a frameshift which resulted in a premature stop codon. The resulting truncated protein does not have the C‐terminal serine/methionine transcription activation domain necessary for interaction with other transcriptional and epigenetic regulators. This mutation likely has a dominant‐negative or gain‐of‐function effect, similar to those observed in other genetic disorders resulting from KAT6B mutations, including Say–Barber–Biesecker–Young–Simpson (SBBYSS) and genitopatellar syndrome (GTPTS). Thus, our subject's phenotype broadens the spectrum of clinical findings associated with mutations in KAT6B. Furthermore, our results suggest that individuals with BPES without a FOXL2 mutation should be tested for KAT6B mutations. The transcriptional and epigenetic regulation mediated by KAT6B appears crucial to early developmental processes, which when perturbed can lead to a wide spectrum of phenotypic outcomes. © 2014 Wiley Periodicals, Inc.