We describe 11 patients, from six independent families, presenting early-onset DEE and a variable association of cleft palate, omphalocele, equinovarus and/or more widely distributed joint contractures, caused by bi-allelic variants of GAD1. Four of six families carried a homozygous variant leading to a truncated protein (Supplementary Fig. 5), supportive of a complete loss-of-function mechanism. This evidence concerns the gene GAD1 and cleft palate.