There is solid evidence that the WHS core phenotypes, such as distinctive craniofacial features, growth delay, and seizures, are caused by haploinsufficiency of several closely linked genes on the short arm of chromosome 4, including WHSC1, WHSC2, TACC3, FGFR3, and LETM1.[11] As FGFR3 is located in the vicinity of the WHS critical region, homozygous null mouse lines have been created for phenotypic assessment, and these have shown to recapitulate some of the skeletal malformation seen in human patients with WHS. This evidence concerns the gene LETM1 and Wolf-Hirschhorn syndrome.