Fronto-otopalatodigital osteodysplasia: Clinical evidence for a single entity encompassing Melnick-Needles syndrome, otopalatodigital syndrome types 1 and 2, and frontometaphyseal dysplasia

Otopalatodigital syndrome type 2 is an X-linked disorder with minimal expre ssion in carrier females and comprises typical facial anomalies and a gener alized bone dysplasia with osteodysplastic changes, brachydactyly, and impa ired survival. Recently several other severe malformations were reported in the condition. Melnick-Needles syndrome is an X-linked dominant disorder. Affected males are usually sporadic cases. The exceptional males born to sy mptomatic women present with a lethal disorder comprising generalized osteo dysplasia, deficiency of the first ray, and facial anomalies strikingly sim ilar to those of otopalatodigital syndrome type 2, We report here on three boys with classical, severe, and lethal otopalatodigital type 2 syndrome, a nd three boys with severe (lethal) Melnick-Needles syndrome, born to affect ed mothers. We suggest that otopalatodigital type 1 and 2, Melnick-Needles syndrome and frontometaphyseal dysplasia, sharing many clinical manifestati ons and a similar mode of inheritance, are variants of the same condition: fronto-otopalatodigital osteodysplasia, The relationships to similar syndro mes (i.e., Saint-Martin-Gardner-Morrisson syndrome, serpentine fibula syndr ome, atelosteogenesis type 3, boomerang dysplasia, and Yunis-Varon syndrome ) are discussed. (C) 2000 Wiley-Liss, Inc.