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Dermatology (Basel, Switzerland) 1999Pseudoxanthoma elasticum (PXE) is an inherited disorder of elastic tissue with many systemic manifestations. The disease varies widely in its degree of expression and... (Review)
Review
Pseudoxanthoma elasticum (PXE) is an inherited disorder of elastic tissue with many systemic manifestations. The disease varies widely in its degree of expression and inheritance patterns and is believed to be considerably underdiagnosed due to lack of familiarity with the condition among physicians. The purpose of this article was to provide an update on important topics in PXE. Common presentations of the disease as well as the histopathology are discussed. The genetics of PXE as well as the importance of early diagnosis and genetic counseling are addressed. Special areas of concern, such as PXE in childhood, are reviewed. Finally, the article concludes with management of the disease and current areas of research.
Topics: Humans; Pseudoxanthoma Elasticum; Skin
PubMed: 10449949
DOI: 10.1159/000018195 -
The Medical Journal of Australia Nov 2014
Topics: Adult; Dermis; Female; Humans; Ophthalmoscopy; Pseudoxanthoma Elasticum
PubMed: 25358583
DOI: 10.5694/mja14.00247 -
Clinical & Experimental Optometry Mar 2011Pseudoxanthoma elasticum (PXE), also known as Groenblad syndrome, is an inherited disorder characterised by mineralisation and fragmentation of elastic fibres in a... (Review)
Review
Pseudoxanthoma elasticum (PXE), also known as Groenblad syndrome, is an inherited disorder characterised by mineralisation and fragmentation of elastic fibres in a number of organs including the skin, eyes and arterial blood vessels. The clinical manifestations of PXE centre on three major organ systems: skin, cardiovascular system and the eyes. This review focuses on the ocular manifestations of pseudoxanthoma elasticum, namely, peau d'orange, angioid streaks and choroidal neovascularisation, the clinical course of patients, the diagnostic approaches and current therapeutic strategies, such as laser photocoagulation whether transpupillary thermotherapy or photodynamic therapy, macular translocation surgery and anti-vascular endothelial growth factor treatment.
Topics: Humans; Pseudoxanthoma Elasticum; Retinal Diseases; Vision Disorders; Visual Acuity
PubMed: 21198842
DOI: 10.1111/j.1444-0938.2010.00559.x -
Survey of Ophthalmology 2003Pseudoxanthoma elasticum is an autosomally inherited disorder that is associated with the accumulation of mineralized and fragmented elastic fibers in the skin, Bruch's... (Review)
Review
Pseudoxanthoma elasticum is an autosomally inherited disorder that is associated with the accumulation of mineralized and fragmented elastic fibers in the skin, Bruch's membrane in the retina, and vessel walls. The ophthalmic and dermatologic expression of pseudoxanthoma elasticum and its vascular complications are heterogeneous, with considerable variation in phenotype, progression, and mode of inheritance. Using linkage analysis and mutation detection techniques, mutations in the ABCC6 gene were recently implicated in the etiology of pseudoxanthoma elasticum. ABCC6 encodes the sixth member of the ATP-binding cassette transporter and multidrug resistance protein family (MRP6). In humans, this transmembrane protein is highly expressed in the liver and kidney. Lower expression was found in tissues affected by pseudoxanthoma elasticum, including skin, retina, and vessel walls. So far, the substrates transported by the ABCC6 protein and its physiological role in the etiology of pseudoxanthoma elasticum are not known. A functional transport study of rat MRP6 suggests that small peptides such as the endothelin receptor antagonist BQ123 are transported by MRP6. Similar molecules transported by ABCC6 in humans may be essential for extracellular matrix deposition or turnover of connective tissue at specific sites in the body. One of these sites is Bruch's membrane. This review is an update on etiology of pseudoxanthoma elasticum, including its clinical and genetic features, pathogenesis, and biomolecular basis.
Topics: Animals; Humans; Molecular Biology; Multidrug Resistance-Associated Proteins; Mutation; Pseudoxanthoma Elasticum; Retinal Diseases
PubMed: 12850230
DOI: 10.1016/s0039-6257(03)00053-5 -
Journal of Cutaneous Pathology Aug 2023Pseudoxanthoma elasticum (PXE) is an autosomal recessive genetic disorder characterized by aberrant fragmentation and calcification of elastic fibers, leading to...
Pseudoxanthoma elasticum (PXE) is an autosomal recessive genetic disorder characterized by aberrant fragmentation and calcification of elastic fibers, leading to characteristic cutaneous, ophthalmic, and cardiovascular manifestations. PXE demonstrates significant phenotypic variability; involvement of the oral mucosa may be the only clue to the diagnosis. Reports on mucous membrane involvement in PXE are scarce. Here, we present a case of PXE-like changes in the oral cavity. A 70-year-old male patient presented with a painless leukoplakic lesion on the soft palate. Biopsy revealed numerous degenerated fibers in the lamina propria. Verhoeff-van Gieson and von Kossa staining confirmed their identity as calcified elastic fibers. A histopathological diagnosis of PXE-like changes was made; the patient was referred to ophthalmology where angioid streaks were visualized fundoscopically. PXE-like changes in the absence of the characteristic genetic mutation have also been reported with or without systemic manifestations. Furthermore, PXE-like changes have been reported in up to 10% of oral biopsy specimens undertaken without clinical suspicion for PXE. Therefore, the significance of such changes in isolation is unclear. Clinicians and pathologists should be aware of the potential oral manifestations of PXE to facilitate prompt diagnosis and subspecialist referral.
Topics: Male; Humans; Aged; Pseudoxanthoma Elasticum; Skin; Elastic Tissue; Palate, Soft; Mutation
PubMed: 37150825
DOI: 10.1111/cup.14445 -
International Journal of Dermatology Jan 2019
Review
Topics: Aged; Biopsy; Diagnosis, Differential; Elastic Tissue; Female; Humans; Pseudoxanthoma Elasticum; Skin; Skin Diseases, Papulosquamous
PubMed: 29907963
DOI: 10.1111/ijd.14093 -
F1000Research 2020Pseudoxanthoma elasticum (PXE) is a rare inherited disorder, characterised by a progressive mineralization and fragmentation of elastic fibres of the skin, retina and...
Pseudoxanthoma elasticum (PXE) is a rare inherited disorder, characterised by a progressive mineralization and fragmentation of elastic fibres of the skin, retina and cardiovascular system. At an initial stage, the skin usually exhibits distinctive lesions and subsequently extra-dermal manifestations. The diagnosis is based on clinical manifestations, histological analysis of the lesions and genetic analysis. This is a case report of a 12-year-old child complaining of painless, mildly itchy yellow papules in the cervical region with 1 year of evolution. PXE is currently an incurable disease and has a favourable prognosis when cardiovascular and retinal complications are prevented and monitored.
Topics: Biopsy; Cardiovascular System; Child; Female; Humans; Pseudoxanthoma Elasticum; Retina; Skin; Ultrasonography
PubMed: 32742638
DOI: 10.12688/f1000research.21431.1 -
Atherosclerosis May 2021Pseudoxanthoma elasticum (PXE) is caused by variants in the ABCC6 gene. It results in calcification in the skin, peripheral arteries and the eyes, but has considerable...
BACKGROUND AND AIMS
Pseudoxanthoma elasticum (PXE) is caused by variants in the ABCC6 gene. It results in calcification in the skin, peripheral arteries and the eyes, but has considerable phenotypic variability. We investigated the association between the ABCC6 genotype and calcification and clinical phenotypes in these different organs.
METHODS
ABCC6 sequencing was performed in 289 PXE patients. Genotypes were grouped as two truncating, mixed, or two non-truncating variants. Arterial calcification mass was quantified on whole body, low dose CT scans; and peripheral arterial disease was measured with the ankle brachial index after treadmill test. The presence of pseudoxanthoma in the skin was systematically scored. Ophthalmological phenotypes were the length of angioid streaks as a measure of Bruchs membrane calcification, the presence of choroidal neovascularizations, severity of macular atrophy and visual acuity. Regression models were built to test the age and sex adjusted genotype-phenotype association.
RESULTS
158 patients (median age 51 years) had two truncating variants, 96 (median age 54 years) a mixed genotype, 18 (median age 47 years) had two non-truncating variants. The mixed genotype was associated with lower peripheral (β: 0.39, 95%CI:-0.62;-0.17) and total (β: 0.28, 95%CI:-0.47;-0.10) arterial calcification mass scores, and lower prevalence of choroidal neovascularizations (OR: 0.41 95%CI:0.20; 0.83) compared to two truncating variants. No association with pseudoxanthomas was found.
CONCLUSIONS
PXE patients with a mixed genotype have less severe arterial and ophthalmological phenotypes than patients with two truncating variants in the ABCC6 gene. Research into environmental and genetic modifiers might provide further insights into the unexplained phenotypic variability.
Topics: Genetic Association Studies; Genotype; Humans; Middle Aged; Peripheral Arterial Disease; Phenotype; Pseudoxanthoma Elasticum
PubMed: 33812167
DOI: 10.1016/j.atherosclerosis.2021.03.012 -
Lancet (London, England) Feb 2013
Topics: Female; Humans; Pseudoxanthoma Elasticum; Skin; Young Adult
PubMed: 23084479
DOI: 10.1016/S0140-6736(12)61130-1 -
Dermatology Online Journal Aug 2009Pseudoxanthoma elasticum is an incurable, autosomal-recessive, genetic disorder that is caused by mutations in the ABCC6 gene. It is characterized by progressive...
Pseudoxanthoma elasticum is an incurable, autosomal-recessive, genetic disorder that is caused by mutations in the ABCC6 gene. It is characterized by progressive mineralization and fragmentation of the elastic fibers in the skin, retina, and blood vessels. The characteristic cutaneous features bring the patient to medical attention, but morbidity is related to the degree of extracutaneous involvement. The disease is progressive with phenotypic variability and no definite genotype-phenotype correlation. Treatment is supportive and is directed at prevention and early detection of adverse ocular and cardiovascular sequelae. We present two siblings with pseudoxanthoma elasticum, who have considerable differences in disease related morbidity, which highlights intra-familiar phenotypic heterogeneity.
Topics: Humans; Male; Middle Aged; Pseudoxanthoma Elasticum
PubMed: 19891925
DOI: No ID Found