Congenital
arthrogryposis (CA) refers to the presence of multiple
contractures at birth. It is a feature of several inherited syndromes, notable amongst them are disorders of
collagen formation. This review aims to characterize disorders that directly or indirectly impact
collagen structure and function leading to CA in search for common phenotypic or pathophysiological features, possible genotype-phenotype correlation, and potential novel treatment approaches based on a better understanding of the underlying pathomechanism. Nine genes, corresponding to five clinical phenotypes, were identified after a literature search. The most notable trend was the extreme phenotype variability. Clinical features across all syndromes ranged from subtle with minimal congenital
contractures, to severe with multiple congenital
contractures and extra-articular features including skin, respiratory, or other manifestations. Five of the identified genes were involved in the function of the
Lysyl Hydroxylase 2 or 3
enzymes, which enable the hydroxylation and/or glycosylation of lysyl residues to allow the formation of the
collagen superstructure. Whilst current treatment approaches are post-natal surgical correction, there are also potential in-utero
therapies being developed.
Cyclosporin A showed promise in treating
collagen VI disorders although there is an associated risk of immunosuppression. The treatments that could be in the clinical trials soon are the splice correction
therapies in
collagen VI-related disorders.