A Genomic Approach to Delineating the Occurrence of Scoliosis in Arthrogryposis Multiplex Congenita

Abstract

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.

Overview of Gene Special Issue “Genetic Conditions Affecting the Skeleton: Congenital, Idiopathic Scoliosis and Arthrogryposis”

“…The search for genes, pathways, and modifier genes for all three conditions is ongoing and may lead to potential therapies. From a total of 908 genes linked with scoliosis and 444 genes linked with AMC identified in the literature, 227 genes were associated with AMC-SC by Latypova and colleagues [ 9 ]. This group of genes is associated with a wide range of cellular functions, including transcription regulation, transmembrane receptor, growth factor, and ion channels.…”