Variable phenotypes of multiple synostosis syndrome in patients with novel NOG mutations

Multiple synostosis syndrome (SYNS) is an autosomal dominant skeletal disorder characterized by facial dysmorphism, progressive fusion of multiple joints, and conductive hearing loss. Currently, three genes, NOG, GDF5, and FGF9, have been identified as causative of SYNS. However, due to the phenotypic and genotypic heterogeneity of SYNS, as well as its extreme rarity, it is difficult to diagnose, either by clinical or genetic means. Here, we describe three unrelated Korean families with three different, novel NOG mutations. These mutations are located on the region of the protein critical for appropriate NOG function. The patients shared the general features of SYNS, but the phenotype was expressed differently both within and between the families. In addition, this phenotypic diversity was irrespective of the age of patients, indicating the importance of surveillance for the full spectrum of SYNS in each affected patient. Our report expands understanding of this rare condition from both clinical and genetic perspectives.