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Pseudoxanthoma elasticum (PXE) is an inherited connective tissue disorder characterized by progressive calcification and fragmentation of elastic fibers in the skin, retina, and arterial walls.
Prevalence is estimated at between 1/25,000 and 1/100,000. The female to male ratio is 2:1 but the cause of this female predominance remains poorly understood.
Skin lesions appear during the second decade of life, with a progressive increase in number and severity during adolescence. The disease is clinically heterogeneous, being limited to only one organ in some patients but affecting all three organs in others. The skin lesions consist of yellow papules that may merge to form plaques. They appear mainly in the flexural areas of the neck and elbows, popliteal spaces and umbilical region, and are accompanied by loosening of the skin around the inguinal folds and armpits. Ophthalmological findings include retinal pigment epithelium anomalies, drusen, angioid streaks (fissuring of the Bruch membrane of the retina), and neovascularization and bleeding leading to retinal hemorrhage and, in many patients, loss of visual acuity. Involvement of the macula may lead to patients being declared as legally blind. Cardiovascular manifestations lead to intermittent claudication of the lower and/or upper limbs due to arteriosclerosis of medium-sized arteries with calcified vessel walls. Transitory ischemic events and angina pectoris are less frequent findings. Gastrointestinal hemorrhage occurs in 5% of cases, mostly during adolescence. Although early reports indicated that affected women may encounter difficulties during pregnancy, more recent studies show that pregnancy in PXE patients is not associated with any specific complications.
PXE is caused by homozygous or compound heterozygous mutations in the ABCC6 gene (16p13.1), which encodes a transmembrane protein from the ATP-binding cassette (ABC) transporter superfamily.
Transmission of the disease is autosomal recessive. Occasional reports of affected family members in two successive generations have been attributed to cases of pseudodominance, rather than an autosomal dominant pattern of inheritance. Genetic counseling should be offered to PXE patients and their families.
Management and treatment
Management should be carried out in specialized centers. The majority of the pathologic manifestations are irreversible but prophylactic measures may be employed to prevent or minimize some of the signs and symptoms, most notably the cardiovascular manifestations. The excess skin folds associated with the cutaneous lesions can be corrected by plastic surgery when they cause esthetic problems.
- Clinical genetics review
- English (2012)