CRELD1 and epilepsy: Monoallelic heterozygous variants might reduce expression and contribute in a multi-causal manner to the susceptibility to heart defects, especially in combination with chromosomal aberrations such as Down syndrome.25 Based on our data, a truncating variant with antimorphic activity combined with a missense variant affecting one of the functional domains of CRELD1 is able to cause severe multisystem disease as in our patient, including muscle weakness, arthrogryposis, developmental delay and epilepsy.