Using comparative patient-parents exome sequencing strategy, a powerful method to detect de novo pathogenic variants involved in human Mendelian genetic diseases [52, 53], we identified the first molecular basis of this association of extreme microcephaly with severely reduced sulcation with RES in a fœtus, a deleterious variant in the ADGRL2 gene, which encodes an adhesion G-Protein-Coupled Receptor (GPCR). This evidence concerns the gene ADGRL2 and microcephaly.