Pseudoxanthoma Elasticum and Cutis Laxa

This chapter focuses on the paediatric manifestations of cutaneous connective tissue disorders characterized by defects in elastic tissue assembly and homeostasis, pseudoxanthoma elasticum and cutis laxa. Pseudoxanthoma elasticum (PXE) is a heritable multisystem disorder characterized by ectopic mineralization and fragmentation of elastic fibres, and is primarily expressed in the skin (as yellowish papules and plaques and laxity of the neck and flexures), retina (as angioid streaks leading to subretinal choroidal neovascularization and bleeding), and cardiovascular system (as premature atherosclerosis of medium-sized arteries). PXE is inherited as an autosomal recessive disorder caused by homozygous or compound heterozygous mutations on the ABCC6 gene, which encodes a cellular transport protein, the exact function and substrate of which remain unknown. Cutis laxa is a heterogeneous group of disorders resulting from genetic mutations that lead to either an absence of elastin or to abnormal elastic fibres. These are all multisystem disorders characterized by loose folds of inelastic skin, and depending on the molecular defect or mechanism, can be associated with aortic arch dilatation, emphysema, hernias, bladder and gastrointestinal diverticulae, and a variety of musculoskeletal or neurological abnormalities.