Orofaciodigital syndromes (OFD) are rare genetical disorders characterized by malformations of the mouth (oris), face (facies), hands and feet (digitus = finger, toe). It is still impossible to fully understand the whole spectrum of all dysfunctions due to OFD, since the expressions of the syndrome vary in each patient. There are various alterations, thoroughly described in literature that can affect the oral cavity such as dental caries, abnormal teeth, enamel hypoplasia, supernumerary teeth and dental agenesis. A syndromic patient with a complex picture showing conditions such as palatine fissures and a severe hypodontia has to be treated using a multidisciplinary approach, and in particular, needs a prosthetic rehabilitation for the restoration of missing dental elements in the arch.