Arthrogryposis multiplex congenita (AMC) describes a group of conditions characterized by the presence of non-progressive congenital contractures in multiple body areas. Scoliosis, defined as a coronal plane spine curvature of ≥10 degrees as measured radiographically, has been reported to occur in approximately 20% of children with AMC. To identify genes that are associated with both scoliosis as a clinical outcome and AMC, we first queried the DECIPHER database for copy number variations (CNVs). Upon query, we identified only two patients with both AMC and scoliosis (AMC-SC). The first patient contained CNVs in three genes (FBN2, MGF10, and PITX1), while the second case had a CNV in ZC4H2. Looking into small variants, using a combination of Human Phenotype Ontogeny and literature searching, 908 genes linked with scoliosis and 444 genes linked with AMC were identified. From these lists, 227 genes were associated with AMC-SC. Ingenuity Pathway Analysis (IPA) was performed on the final gene list to gain insight into the functional interactions of genes and various categories. To summarize, this group of genes encompasses a diverse group of cellular functions including transcription regulation, transmembrane receptor, growth factor, and ion channels. These results provide a focal point for further research using genomics and animal models to facilitate the identification of prognostic factors and therapeutic targets for AMC.
Keywords: Amyoplasia; CNV (copy number variant); DA (distal arthrogryposis); DECIPHER (DatabasE of genomiC variation and Phenotype in Humans using Ensemble Resources); HPO (human phenotype ontology); IGF2; IPA (ingenuity pathway analysis); MYOD; akinesia; scoliosis.