Taken together, data from the Fzd2INS/INS and Prx1-Cre Fzd2fl mutants suggest that shortened limbs observed in FZD2-associated AD-RS/OMOD2 patients result from FZD2 deficiency in developing limb bud and are caused by defects in both canonical and non-canonical Wnt signaling. Here, FZD2 is linked to Alzheimer disease.