Clinical characteristics and mutation profiles of Collagen-VI related myopathy

Abstract

Background: collagen VI-related myopathy is one of the most common type of congenital muscular dystrophy. This study was aimed to describe clinical, genetic characteristics, and identify their association of collagen VI-related myopathy patients. Methods: We enrolled 23 patients with collagen VI-related myopathy who were confirmed to have pathogenic mutation of COL6A1, COL6A2, COL6A3. Medical record was reviewed retrospectively. Results: Among 23 cases, 10 patients (43%) had congenital orthopedic problems such as torticollis, congenital hip dislocation or arthrogryposis congenita. Three patients (13%) never walked and 7 (35%) lost their walking ability later at the mean age of 10. Hyperlaxity of distal joints, contracture of proximal joints, and scoliosis were noted each in 12 (52%) patients. Six patients (26%) used mechanical ventilator support. Clinical features and courses varied by patients. Patients were categorized as Ullrich type in 11 (48%), Bethlem type in 4 (17%), limb-girdle type in 3 (13%), and undetermined in 5 (22%). All patients showed sarcolemma-specific collagen VI deficiency in immunohistochemistry of muscle. Mutations for COL6A1, COL6A2, and COL6A3 were found each in 15 (65%), 3 (13%), and 5 (22%) of each group of patients. All had heterozygous variants and most of mutations located in triple helical domain. Five novel variants were detected. There was no clear association between genotype and phenotype. Multiple congenital orthopedic problems including arthrogryposis multiplex congenital were frequently noted in early-severe group. Conclusion: We verified heterogeneity in clinical features of collagen VI myopathy as well as in pathology and genotype. Multiple congenital orthopedic problems might suggest poor prognosis, without clear genotpye or phenotype association to clinical severity