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JAMA Dermatology Jan 2022
Topics: Humans; Pseudoxanthoma Elasticum
PubMed: 34787669
DOI: 10.1001/jamadermatol.2021.4059 -
Handbook of Clinical Neurology 2015Pseudoxanthoma elasticum (PXE) is characterized by elastic tissue fragmentation and calcification. The deterioration of elastic fibers leads to characteristic yellowish... (Review)
Review
Pseudoxanthoma elasticum (PXE) is characterized by elastic tissue fragmentation and calcification. The deterioration of elastic fibers leads to characteristic yellowish papules and plaques (pseudoxanthomas) and retinal angioid streaks. Although these findings may begin in childhood, the diagnosis is typically not made until the second or third decade after the skin and retinal findings become more prominent. Cerebrovascular complications include brain infarction due to narrowing and occlusion of cerebral arteries and aneurysm formation. Intracranial hemorrhage can occur in the absence of aneurysm, and gastrointestinal hemorrhage is common. Peripheral arterial vascular disease can lead to intermittent leg claudication. A skin biopsy often demonstrates calcified elastic fibers, even in a mildly affected area of skin. The inheritance is autosomal recessive, although heterozygotes may exhibit some features of the disease. PXE is due to mutation of the ABCC6 gene on chromosome 16. There is no treatment, but certain lifestyle modifications may limit the complications. The potential for retinal hemorrhage has led to recommendations for limitations of contact sports or other activities that might facilitate eye trauma. Other recommendations include maintaining a normal lipid profile, avoidance of aspirin and nonsteroidal anti-inflammatory agents, and limiting dietary calcium intake.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Humans; Multidrug Resistance-Associated Proteins; Mutation; Pseudoxanthoma Elasticum
PubMed: 26564082
DOI: 10.1016/B978-0-444-62702-5.00015-9 -
Medicina Clinica Apr 2019
Topics: Adult; Eye; Female; Humans; Multidrug Resistance-Associated Proteins; Mutation; Pseudoxanthoma Elasticum
PubMed: 30001896
DOI: 10.1016/j.medcli.2018.05.025 -
The Journal of Dermatology Oct 2002Pseudoxanthoma elasticum (PXE) is a heritable disease characterized by dermal, ocular, and vascular lesions that result from degeneration of the elastic fibers.... (Review)
Review
Pseudoxanthoma elasticum (PXE) is a heritable disease characterized by dermal, ocular, and vascular lesions that result from degeneration of the elastic fibers. Recently, the ATP-binding cassette subfamily C member 6 (ABCC6) gene has been demonstrated to be responsible for PXE, and 43 mutations have been identified to date. However, it is still unknown now mutations in the ABCCC6 gene can lead to manifestations of PXE.
Topics: Humans; Multidrug Resistance-Associated Proteins; Mutation; Mutation, Missense; Polymorphism, Genetic; Pseudoxanthoma Elasticum
PubMed: 12432991
DOI: 10.1111/j.1346-8138.2002.tb00190.x -
Archives of Disease in Childhood Jul 2005Pseudoxanthoma elasticum (PXE) is a rare multisystem disorder characterised by progressive calcification and fragmentation of elastic fibres. Recent genetic advances... (Review)
Review
Pseudoxanthoma elasticum (PXE) is a rare multisystem disorder characterised by progressive calcification and fragmentation of elastic fibres. Recent genetic advances have identified the underlying defect to the ABCC6 gene on chromosome 16p13.1. Patients typically develop cutaneous, ocular, and cardiovascular manifestations but there is considerable phenotypic variability. The skin changes are usually apparent in adulthood, and rarely observed in childhood. Since the prognosis of PXE largely depends on the extent of extracutaneous organ involvement early recognition, intervention and lifestyle adjustments are important to reduce morbidity. First-degree family members should be carefully examined for any cutaneous or ophthalmologic features of PXE.
Topics: Cardiovascular Diseases; Child; Chromosomes, Human, Pair 16; Eye Diseases; Humans; Multidrug Resistance-Associated Proteins; Pseudoxanthoma Elasticum; Skin Diseases
PubMed: 15970621
DOI: 10.1136/adc.2004.062075 -
Genetics in Medicine : Official Journal... Jan 2021Pseudoxanthoma elasticum (PXE) is a heritable disorder affecting elastic fibers in the skin, eyes, and cardiovascular system. It is caused by biallelic pathogenic...
PURPOSE
Pseudoxanthoma elasticum (PXE) is a heritable disorder affecting elastic fibers in the skin, eyes, and cardiovascular system. It is caused by biallelic pathogenic variants in the ABCC6 gene. To date, over 300 ABCC6 variants are associated with PXE, more than half being missense variants. Correct variant interpretation is essential for establishing a direct link between the variant and the patient's phenotype and has important implications for diagnosis and treatment.
METHODS
We used a systematic approach for interpretation of 271 previously reported and 15 novel ABCC6 missense variants, based on the semiquantitative classification system Sherloc.
RESULTS
Only 35% of variants were very likely to contribute directly to disease, in contrast to reported interpretations in ClinVar, while 59% of variants are currently of uncertain significance (VUS). Subclasses were created to distinguish VUS that are leaning toward likely benign or pathogenic, increasing the number of (likely) pathogenic ABCC6 missense variants to 47%.
CONCLUSION
Besides highlighting discrepancies between the Sherloc, American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG-AMP), ClinVar, and Leiden Open Variation Database (LOVD) classification, our results emphasize the need for segregation analysis, functional assays, and detailed evidence sharing in variant databases to reach a confident interpretation of ABCC6 missense variants and subsequent appropriate genetic and preconceptual counseling.
Topics: Humans; Multidrug Resistance-Associated Proteins; Mutation; Mutation, Missense; Phenotype; Pseudoxanthoma Elasticum
PubMed: 32873932
DOI: 10.1038/s41436-020-00945-6 -
JAMA Dermatology Jan 2022
Topics: Cutis Laxa; Humans; Pseudoxanthoma Elasticum; Skin
PubMed: 34787648
DOI: 10.1001/jamadermatol.2021.4063 -
QJM : Monthly Journal of the... Jul 2021
Topics: Angioid Streaks; Fluorescein Angiography; Humans; Pseudoxanthoma Elasticum
PubMed: 32502256
DOI: 10.1093/qjmed/hcaa190 -
Journal of the American Academy of... Jul 2004
Review
Topics: Animals; Humans; Pseudoxanthoma Elasticum
PubMed: 15243491
DOI: 10.1016/j.jaad.2004.01.015 -
Der Ophthalmologe : Zeitschrift Der... Jun 2006Pseudoxanthoma elasticum (PXE) is an inherited disorder that is associated with accumulation of mineralized and fragmented elastic fibers in the skin, vessel walls, and... (Review)
Review
Pseudoxanthoma elasticum (PXE) is an inherited disorder that is associated with accumulation of mineralized and fragmented elastic fibers in the skin, vessel walls, and Bruch's membrane. Clinically, patients exhibit characteristic lesions of the skin (soft, ivory-colored papules in a reticular pattern that predominantly affect the neck), the posterior segment of the eye (peau d'orange, angioid streaks, choroidal neovascularizations), and the cardiovascular system (peripheral arterial occlusive disease, coronary occlusion, gastrointestinal bleeding). There is no causal therapy. Recent studies suggest that PXE is inherited almost exclusively as an autosomal recessive trait. Its prevalence has been estimated to be 1:25,000-100,000. The ABCC6 gene on chromosome 16p13.1 is associated with the disease. Mutations within the ABCC6 gene cause reduced or absent transmembraneous transport that leads to accumulation of substrate and calcification of elastic fibers. Although based on clinical features the diagnosis appears readily possible, variability in phenotypic expressions and the low prevalence may be responsible that the disease is underdiagnosed. This review covers current knowledge of PXE and presents therapeutic approaches.
Topics: Choroidal Neovascularization; Humans; Practice Guidelines as Topic; Practice Patterns, Physicians'; Pseudoxanthoma Elasticum
PubMed: 16763870
DOI: 10.1007/s00347-006-1353-4