Ullrich Congenital Dystrophy and Bethlem Myopathy: Current Knowledge on the Clinical Spectrum, Pathogenesis, and Future Therapeutic Avenues of Collagen VI Related Muscular Dystrophies

Abstract

Ullrich congenital muscular dystrophy (UCMD) is a genetically and clinically heterogeneous muscle disorder causing severe muscle weakness with proximal joint contractures and distal hyperlaxity linked to collagen VI deficiency. It was initially described within the wider group of muscular congenital dystrophies. Collagen VI is an extracellular matrix protein forming a microfibrillar network. The protein is composed of three different α-chains encoded by separate genes named COL6A1, COL6A2, and COL6A3 in humans. Mutations of collagen VI gene are also responsible for Bethlem myopathy (BM), a relatively mild dominantly inherited disorder characterised by proximal weakness and distal joint contractures that was previously believed to be a completely separate entity. The pathogenesis of both diseases is still poorly understood. However, some recent data, obtained from experiments mouse models and from human myoblast cultures provide valuable insights into the pathogenesis of UCMD. A potential mitochondrial involvement may become the focus of specific therapeutic approaches. In this review we emphasise the typical clinical and biochemical findings that will help the paediatrician to identify collagenopathies within the complex diagnostic group of congenital muscular dystrophies, and outline the current understanding of UCMD pathogenesis, management, and potential therapeutic avenues. © 2009 Bentham Science Publishers Ltd.