Bi-allelic pathogenic loss-of-function (LoF) variants of POLE have been detected in IMAGE syndrome (OMIM 614732), which is characterized by intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies, as well as in FILS syndromes (OMIM 615139), which is characterized by malar hypoplasia, livedo, short stature, and immunodeficiency. Here, POLE is linked to Metaphyseal dysplasia.