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A comprehensive review of reported heritable nogginâassociated syndromes and proposed clinical utility of one broadly inclusive diagnostic term: NOG ârelatedâsymphalangism spectrum disorder ( NOG âSSD)
The NOG gene encodes noggin, a secreted polypeptide that is important for regulating multiple signaling pathways during human development, particularly in cartilage and bone. The hallmark of NOG ârelated syndromes is proximal symphalangism, defined by abnormal fusion of the proximal interphalangeal joints of the hands and feet. Many additional features secondary to NOG mutations are commonly but inconsistently observed, including a characteristic facies with a hemicylindrical nose, congenital conductive hearing loss due to stapes fixation, and hyperopia. The variable clinical presentations led to the designation of five different autosomal dominant syndromes, all subsequently found to have resulted from NOG mutations. These include (1) proximal symphalangism; (2) multiple synostoses syndrome 1; (3) stapes ankylosis with broad thumbs and toes; (4) tarsalâcarpal coalition syndrome; and (5) brachydactyly type B2. Herein, we review the phenotypic features associated with mutations in the NOG gene, demonstrating the overlapping characteristics of these syndromes. Due to the variable phenotypic spectrum within families and among families with the same mutation, we propose a unifying term, NOG ârelated symphalangism spectrum disorder ( NOG âSSD), to aid in the clinical recognition and evaluation of all affected individuals with these phenotypes. These NOG gene variants are available in a new locusâspecific database ( https://NOG.lovd.nl ).Hum Mutat 32:1â10, 2011. © 2011 WileyâLiss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87082/1/21515_ftp.pd