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| {{SK}} Forme fruste pseudoxanthoma elasticum; Gronblad Strandberg syndrome; Gronblad-Strandberg syndrome | | {{SK}} Forme fruste pseudoxanthoma elasticum; Gronblad Strandberg syndrome; Gronblad-Strandberg syndrome |
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| ==Overview== | | ==[[Pseudoxanthoma elasticum overview|Overview]]== |
| '''Pseudoxanthoma elasticum''' (PXE) is a [[genetic disease]] that is caused by [[Recessive#Autosomal recessive gene|autosomal recessive mutations]] in the ''[[ABCC6]]'' gene on the short arm of [[chromosome 16]] (16p13.1). PXE causes fragmentation and mineralization of elastic fibers in some tissues. The most common problems arise in the [[skin]] and [[eye]]s, and later in [[blood vessel]]s in the form of premature [[atherosclerosis]].<ref name=Chassaing>{{cite journal |author=Chassaing N, Martin L, Calvas P, Le Bert M, Hovnanian A |title=Pseudoxanthoma elasticum: a clinical, pathophysiological and genetic update including 11 novel ABCC6 mutations |journal=J. Med. Genet. |volume=42 |issue=12 |pages=881-92 |year=2005 |pmid=15894595 |doi=10.1136/jmg.2004.030171}}</ref>
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| ==Historical Perspective== | | ==[[Pseudoxanthoma elasticum historical perspective|Historical Perspective]]== |
| The first description of PXE that distinguished it from other [[xanthoma]]tous conditions was by Dr Ferdinand-Jean Darrier in 1896.<ref>Darier FJ (1896). Pseudoxanthoma elasticum. ''Monatschr Prakt Dermatol'' '''23''':609-17.</ref> The eponym "Grönblad-Strandberg syndrome" is used in older literature, after two physicians who made further discoveries in the disease manifestations.<ref>{{WhoNamedIt|synd|1059}}</ref>
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| PXE has the distinction of being the only disease for which a layperson is the inventor of the gene, ''ABCC6''. Sharon F. Terry, co-founder of PXE International with her husband, Patrick F. Terry, worked with scientists to discover and patent the gene in 2000.<ref name=LeSaux/> The Terrys' two children have pseudoxanthoma elasticum.<ref>{{cite journal |author=Terry SF, Terry PF, Rauen KA, Uitto J, Bercovitch LG |title=Advocacy groups as research organizations: the PXE International example |journal=Nat. Rev. Genet. |volume=8 |issue=2 |pages=157-64 |year=2007 |pmid=17230202 |doi=10.1038/nrg1991}}</ref>
| | ==[[Pseudoxanthoma elasticum classification|Classification]]== |
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| ==Classification== | | ==[[Pseudoxanthoma elasticum pathophysiology|Pathophysiology]]== |
| The diagnostic criteria for PXE are the typical skin biopsy appearance and the presence of angioid streaks in the retina. Other systems have become somewhat outdated by the discovery of the ''ABCC6'' mutations.<ref name=Chassaing/>
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| ==Pathophysiology== | | ==[[Pseudoxanthoma elasticum causes|Causes]]== |
| In PXE, the calcification (accumulation of [[calcium in biology|calcium]]) and fragmentation of the [[elastin]]-containing fibers in [[connective tissue]], but primarily in the midsized [[artery|arteries]].<ref>{{cite journal |author=Gheduzzi D, Sammarco R, Quaglino D, Bercovitch L, Terry S, Taylor W, Ronchetti I |title=Extracutaneous ultrastructural alterations in pseudoxanthoma elasticum |journal=Ultrastructural pathology |volume=27 |issue=6 |pages=375-84 |year=2003 |pmid=14660276}}</ref>
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| Strong genetic linkage was found with mutations in the ''[[ABCC6]]'' gene, but the exact mechanism by which this protein (which is a membrane transporter from the large [[ATP-binding cassette transporter genes|ATP-binding cassette transporter]] family) influences the disease course is unknown; the protein is expressed in most organs, but mainly in the [[liver]] and [[kidney]]. It is unclear in what way this would lead to abnormalities in skin, eyes and blood vessels. It is thought that particular mutations do not cause a more severe or less severe form of the disease. Given the variations in age of onset and severity it is likely that other unknown risk factors (genetic and dietary) may be involved.<ref name=Chassaing/> Premature atherosclerosis is also associated with mutations in the ''[[ABCC6]]'' gene, even in those without PXE.<ref name="pmid12176944">{{cite journal |author=Trip MD, Smulders YM, Wegman JJ, ''et al'' |title=Frequent mutation in the ABCC6 gene (R1141X) is associated with a strong increase in the prevalence of coronary artery disease |journal=Circulation |volume=106 |issue=7 |pages=773-5 |year=2002 |pmid=12176944 |doi=}}</ref>
| | ==[[Pseudoxanthoma elasticum differential diagnosis|Differentiating Pseudoxanthoma elasticum from other Diseases]]== |
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| A syndrome almost indistinguishable from hereditary PXE has been described in patients with [[hemoglobinopathy|hemoglobinopathies]] ([[sickle-cell disease]] and [[thalassemia]]) through a poorly understood mechanism.<ref name=Chassaing/>
| | ==[[Pseudoxanthoma elasticum epidemiology and demographics|Epidemiology and Demographics]]== |
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| ==Genetics== | | ==[[Pseudoxanthoma elasticum risk factors|Risk Factors]]== |
| 80% of clinical cases of pseudoxanthoma elasticum have detectable mutations in the ''ABCC6'' gene.<ref>{{cite journal |author=Ringpfeil F, Lebwohl MG, Christiano AM, Uitto J |title=Pseudoxanthoma elasticum: mutations in the MRP6 gene encoding a transmembrane ATP-binding cassette (ABC) transporter |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=97 |issue=11 |pages=6001-6 |year=2000 |pmid=10811882 |doi=10.1073/pnas.100041297}}</ref><ref>{{cite journal |author=Bergen AA, Plomp AS, Schuurman EJ, ''et al'' |title=Mutations in ABCC6 cause pseudoxanthoma elasticum |journal=Nat. Genet. |volume=25 |issue=2 |pages=228-31 |year=2000 |pmid=10835643 |doi=10.1038/76109}}</ref><ref name=LeSaux>{{cite journal |author=Le Saux O, Urban Z, Tschuch C, ''et al'' |title=Mutations in a gene encoding an ABC transporter cause pseudoxanthoma elasticum |journal=Nat. Genet. |volume=25 |issue=2 |pages=223-7 |year=2000 |pmid=10835642 |doi=10.1038/76102}}</ref><ref>{{cite journal |author=Struk B, Cai L, Zäch S, ''et al'' |title=Mutations of the gene encoding the transmembrane transporter protein ABC-C6 cause pseudoxanthoma elasticum |journal=J. Mol. Med. |volume=78 |issue=5 |pages=282-6 |year=2000 |pmid=10954200 |doi=}}</ref> Mutations in almost all parts of the gene have been described, of all types (missense, nonsense, splice alteration, insertion, small deletion or large deletion). Although there have been reports of [[Dominance relationship|autosomal dominant]] inheritance, the inheritance is typically autosomal recessive (both parents need to be carriers, and there is a 25% chance that a child will inherit ''both'' abnormal copies of the gene and therefore develop the condition).<ref name=Chassaing/>
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| ==Epidemiology and Demographics== | | ==[[Pseudoxanthoma elasticum natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
| The reported prevalence of pseudoxanthoma elasticum is about 1:25,000. Females are twice as likely to be affected as males. The disease occurs in all ethnicities, but South Africans are more likely to have PXE as a result of a [[founder effect]] (i.e. it was relatively prevalent in the small group of people from whom most South Africans descend).<ref name=Chassaing/>
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| ==Diagnosis== | | ==Diagnosis== |
| Usually, pseudoxanthoma elasticum affects the skin first, often in childhood but frequently later. Small, yellowish papular lesions form and cutaneous laxity mainly affects the neck, [[Armpit|axillae]] (armpits), groin, and flexural creases (the inside parts of the elbows and knees). Skin may become lax and redundant. Many individuals have "oblique mental creases" (diagonal grooves of the chin).<ref name=Chassaing/>
| | [[Pseudoxanthoma elasticum history and symptoms| History and Symptoms]] | [[Pseudoxanthoma elasticum physical examination | Physical Examination]] | [[Pseudoxanthoma elasticum laboratory findings|Laboratory Findings]] | [[Pseudoxanthoma elasticum CT|CT]] | [[Pseudoxanthoma elasticum other imaging findings|Other Imaging Findings]] | [[Pseudoxanthoma elasticum other diagnostic studies|Other Diagnostic Studies]] |
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| PXE first affects the retina through a dimpling of the [[Bruch's membrane|Bruch membrane]] (a thin membrane separating the blood vessel-rich layer from the pigmented layer of the [[retina]]), that is only visible during [[ophthalmologic]] examinations. This is called [[peau d'orange]] (a French term meaning that the retina resembles the skin of an orange). Eventually the mineralization of the elastic fibers in the Bruch membrane create cracks ([[angioid streaks]]) that radiate out from the optic nerve. Angioid streaks themselves do not cause distortion of vision, even if they cross into the foveal area. This symptom is present almost all PXE patients and is usually noticed a few years after the onset of cutaneous [[wikt:lesion|lesions]]. These cracks may allow small blood vessels that were originally held back by Bruch's membrane to penetrate the retina. These blood vessels sometimes leak, and it's these retinal [[wikt:hemorrhage|hemorrhages]] that may lead to the loss of central vision. Vision loss is a major issue in many PXE patients.<ref name=Chassaing/>
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| PXE may affect the gastrointestinal and cardiovascular systems. In the digestive tract, the principal symptom is [[gastrointestinal bleeding]], usually from the [[stomach]]. This occurs in very small number of patients. In the circulatory system, [[intermittent claudication]] (leg pain during walking which resolves at rest) is a prominent feature, although at later stages [[coronary artery disease]] and [[myocardial infarction]] may occur.<ref name=Chassaing/>
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| ==Treatment== | | ==Treatment== |
| There is no treatment that directly interferes with the disease process, although dietary restriction of calcium has been tried with limited results. For excessive areas of skin, [[plastic surgery]] may be needed. For the growth of abnormal blood vessels in the retina, [[laser eye surgery]] may be needed in forms similar to that used in [[diabetic retinopathy]] (eye damage due to diabetes). Cardiovascular disease is treated as in individuals without PXE. Some recommend avoidance of medication that would increase bleeding risk, such as [[aspirin]].<ref name=Chassaing/>
| | [[Pseudoxanthoma elasticum medical therapy|Medical Therapy]] | [[Pseudoxanthoma elasticum surgery|Surgery]] | [[Pseudoxanthoma elasticum primary prevention|Primary Prevention]] |[[Pseudoxanthoma elasticum secondary prevention|Secondary Prevention]] | [[Pseudoxanthoma elasticum cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] |[[Pseudoxanthoma elasticum future or investigational therapies|Future or Investigational Therapies]] |
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| ==References==
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| {{reflist|2}}
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| ==External links==
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| * [http://www.pxe.org/ PXE International]
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| * {{GeneTests|pxe}}
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| * {{NLM|pseudoxanthomaelasticum}}
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| [[Category:Genetic Disease]] | | [[Category:Genetic Disease]] |