Additionally, no known variants in Notch pathway co-repressor genes have been associated with AOS, whereas numerous NOTCH1 and DLL4 variants have been associated with this developmental syndrome [39], and several of the autosomal dominant NOTCH1 and DLL4 AOS alleles encode nonsense variants that are unlikely to generate a protein with dominant-negative effects. This evidence concerns the gene NOTCH1 and Adams-Oliver syndrome.