A Comprehensive Review of Reported Heritable Noggin-Associated Syndromes and Proposed Clinical Utility of One Broadly Inclusive Diagnostic Term: NOG-Related-Symphalangism Spectrum Disorder (NOG-SSD)

作者：Potti Tommy A; Petty Elizabeth M; Lesperance Marci M^*

来源：Human Mutation, 2011, 32(8): 877-886.

DOI：10.1002/humu.21515

• NOG
• noggin
• proximal symphalangism
• stapes ankylosis

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-related 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) tarsal-carpal 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-related symphalangism spectrum disorder (NOG-SSD), to aid in the clinical recognition and evaluation of all affected individuals with these phenotypes. These NOG gene variants are available in a new locus-specific database (https://NOG.lovd.nl). Hum Mutat 32:877-886, 2011.

• 出版日期2011-8