Atypical skeletal changes in otopalatodigital syndrome type II: Phenotypic overlap among otopalatodigital syndrome type II, boomerang dysplasia, atelosteogenesis type I and type III, and lethal male phenotype of Melnick-Needles syndrome

Abstract

We report on 2 cases of otopalatodigital syndrome type II (OPD II) with atypical skeletal changes, overlapping those of boomerang dysplasia, atelosteogenesis type I (AO I) and type III (AO III), and the lethal male phenotype of Melnick-Needles syndrome. One patient exhibited strikingly broad, bowed femora, which resembled those of boomerang dysplasia. The other patient possessed conspicuous undertubulation of the long bones, defective ossification of the spine, and severe undermineralization of the calvaria, which may have caused diagnostic confusion with AO I, AO III, and the lethal male phenotype of Melnick-Needles syndrome. OPD II is transmitted as an X-linked recessive trait, whereas AO I, AO III, and boomerang dysplasia are considered to result from a new dominant mutation, and Melnick-Needles syndrome is inherited as an X-linked dominant trait. Accordingly, differential diagnosis is mandatory to provide the affected families with adequate genetic counseling. Awareness of these skeletal changes in OPD II will prevent the misdiagnosis of this entity as other disorders. Furthermore, the phenotypic overlap among these disorders may expand the entities that constitute the OPD-Larsen dysplasia family proposed by Spranger [1985].