A decade later, an increasing number of cases harboring large intragenic or whole gene deletions/duplications of the MED13L gene, chromosomal translocation disrupting the MED13L gene, de novo frameshift variants, nonsense mutations, and splice site mutations were published, exhibiting moderate ID, severe speech impairment, motor developmental delay, facial deformity and/or CHD, and these were recognized as MED13L haploinsufficiency syndrome [4–11]. This evidence concerns the gene MED13L and Down syndrome.