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<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>Pseudoxanthoma Elasticum - GeneReviews® - NCBI Bookshelf</title>
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<meta name="citation_title" content="Pseudoxanthoma Elasticum">
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<meta name="citation_publisher" content="University of Washington, Seattle">
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<meta name="citation_date" content="2020/06/04">
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<meta name="citation_author" content="Sharon F Terry">
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<meta name="citation_author" content="Jouni Uitto">
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<meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK1113/">
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<meta name="citation_keywords" content="PXE">
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<meta name="citation_keywords" content="PXE">
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<meta name="citation_keywords" content="ATP-binding cassette sub-family C member 6">
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<meta name="citation_keywords" content="ABCC6">
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<meta name="citation_keywords" content="Pseudoxanthoma Elasticum">
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<meta name="DC.Title" content="Pseudoxanthoma Elasticum">
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<meta name="DC.Contributor" content="Sharon F Terry">
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<meta name="DC.Contributor" content="Jouni Uitto">
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<meta name="DC.Date" content="2020/06/04">
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<meta name="description" content="Pseudoxanthoma elasticum (PXE) is a systemic disorder that affects the elastic tissue of the skin, the eye, and vascular system. Individuals most commonly present with angioid streaks of the retina found on routine eye examination or associated with retinal hemorrhage and/or characteristic papules in the skin. The most frequent cause of morbidity and disability in PXE is reduced vision due to complications of subretinal neovascularizations and macular atrophy. Other manifestations include premature gastrointestinal angina and/or bleeding, intermittent claudication of arm and leg muscles, stroke, renovascular hypertension, and cardiovascular complications (angina/myocardial infarction). Most affected individuals live a normal life span.">
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<meta name="og:description" content="Pseudoxanthoma elasticum (PXE) is a systemic disorder that affects the elastic tissue of the skin, the eye, and vascular system. Individuals most commonly present with angioid streaks of the retina found on routine eye examination or associated with retinal hemorrhage and/or characteristic papules in the skin. The most frequent cause of morbidity and disability in PXE is reduced vision due to complications of subretinal neovascularizations and macular atrophy. Other manifestations include premature gastrointestinal angina and/or bleeding, intermittent claudication of arm and leg muscles, stroke, renovascular hypertension, and cardiovascular complications (angina/myocardial infarction). Most affected individuals live a normal life span.">
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class="wsprkl btn" title="Jump to next match">▶</a></nav></nav></div><div id="jr-epub-interstitial" class="hidden"></div><div id="jr-content"><article data-type="main"><div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><div class="fm-sec"><h1 id="_NBK1113_"><span class="title" itemprop="name">Pseudoxanthoma Elasticum</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm">Synonym: PXE</div><p class="contribs">Terry SF, Uitto J.</p><p class="fm-aai"><a href="#_NBK1113_pubdet_">Publication Details</a></p><p><em>Estimated reading time: 22 minutes</em></p></div></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="pxe.Summary" itemprop="description"><h2 id="_pxe_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p>Pseudoxanthoma elasticum (PXE) is a systemic disorder that affects the elastic tissue of the skin, the eye, and vascular system. Individuals most commonly present with angioid streaks of the retina found on routine eye examination or associated with retinal hemorrhage and/or characteristic papules in the skin. The most frequent cause of morbidity and disability in PXE is reduced vision due to complications of subretinal neovascularizations and macular atrophy. Other manifestations include premature gastrointestinal angina and/or bleeding, intermittent claudication of arm and leg muscles, stroke, renovascular hypertension, and cardiovascular complications (angina/myocardial infarction). Most affected individuals live a normal life span.</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The clinical diagnosis of PXE is established in a proband with characteristic skin lesions and at least one characteristic retinal finding. When eye findings are characteristic, but skin findings are equivocal, identification of calcified dystrophic elastic fibers using a von Kossa or similar stain on a biopsy of potentially lesional skin establishes the diagnosis.</p><p>The molecular diagnosis of PXE is established in a proband by the presence of biallelic <i>ABCC6</i> pathogenic variants identified on molecular genetic testing.</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment of manifestations:</i> Management requires coordinated input from multidisciplinary specialists; care by a retina specialist including intraocular injection of anti-angiogenic drugs for the treatment of macular neovascularization when indicated; standard-of-care interventions for gastrointestinal bleeding, claudication, stroke, renovascular hypertension, and cardiovascular complications (angina and/or myocardial infarction).</p><p><i>Surveillance:</i> Routine examination by a retina specialist; follow up as recommended by treating physicians for vascular manifestations.</p><p><i>Agents/circumstances to avoid:</i> Contact sports or racquet sports without appropriate eye and head protection; aspirin and nonsteroidal anti-inflammatory medications because of increased risk of gastrointestinal bleeding; smoking because of its vasoconstrictive properties.</p><p><i>Pregnancy management:</i> Vaginal delivery appears safe for the retina of women with PXE if no active choroidal neovascularization (CNV) is present. Women with PXE should have a retinal examination to check for active CNV, as angioid streaks alone are not an indication for medical interventions during delivery.</p></div><div><h4 class="inline">Genetic counseling.</h4><p>PXE is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic heterozygote (carrier), and a 25% chance of being unaffected and not a carrier. If both <i>ABCC6</i> pathogenic variants have been identified in the family, carrier testing for at-risk family members, prenatal testing for pregnancies at increased risk, and preimplantation genetic testing are possible.</p></div></div><div id="pxe.Diagnosis"><h2 id="_pxe_Diagnosis_">Diagnosis</h2><p>Formal diagnostic criteria for pseudoxanthoma elasticum (PXE) have been established [<a class="bibr" href="#pxe.REF.uitto.2014.567" rid="pxe.REF.uitto.2014.567">Uitto et al 2014</a>].</p><div id="pxe.Suggestive_Findings"><h3>Suggestive Findings</h3><p>PXE <b>should be suspected</b> in individuals with the following clinical findings and family history.</p><p>
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<b>Clinical findings</b>
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</p><ul><li class="half_rhythm"><div>
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<b>Skin</b>
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</div><ul><li class="half_rhythm"><div>Papules (darker than the skin color), usually seen on the lateral aspect of the neck or the flexural creases, such as the antecubital fossae, axillae, groin, or popliteal fossae</div></li><li class="half_rhythm"><div>Plaques formed by coalescence of papules</div></li><li class="half_rhythm"><div>Loose, slack, or droopy, redundant skin (especially of the neck, axilla, and groin) that occurs with time</div></li></ul></li><li class="half_rhythm"><div>
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<b>Eye</b>
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</div><ul><li class="half_rhythm"><div class="half_rhythm"><i>Peau d'orange</i> generally appearing in the first decade and the late second decade, characterized by diffuse mottling of the fundus</div></li><li class="half_rhythm"><div class="half_rhythm">Retinal angioid streaks often appearing in the second decade, consisting of broad grayish to reddish-brown irregular lines caused by breaks in Bruch's membrane* that appear to radiate outward from the optic disk or peripapillary region in a pattern that resembles blood vessels; hence the term "angioid"</div><div class="half_rhythm">* Bruch's membrane is the elastin-rich tissue layer of the choroid between the retina and the choriocapillaris.</div><div class="half_rhythm">Note: Fluorescein angiography may be necessary to confirm this retinal finding.</div></li></ul></li><li class="half_rhythm"><div><b>Gastrointestinal bleeding,</b> particularly the stomach. The characteristic yellow mucosal lesions of PXE can be seen on gastroscopy.</div></li><li class="half_rhythm"><div><b>Vascular.</b> Beginning in the second decade of life, almost all individuals with PXE develop intermittent claudication.</div></li></ul><p><b>Family history</b> is consistent with autosomal recessive inheritance. Note: Pseudodominant inheritance (i.e., an autosomal recessive condition present in individuals in two or more generations) has been reported in some families [<a class="bibr" href="#pxe.REF.bergen.2006.704" rid="pxe.REF.bergen.2006.704">Bergen 2006</a>, <a class="bibr" href="#pxe.REF.ringpfeil.2006.782" rid="pxe.REF.ringpfeil.2006.782">Ringpfeil et al 2006</a>, <a class="bibr" href="#pxe.REF.legrand.2017.909" rid="pxe.REF.legrand.2017.909">Legrand et al 2017</a>].</p></div><div id="pxe.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p>The diagnosis of PXE can be <b>established</b> in a proband based on clinical findings or by identification of biallelic pathogenic (or likely pathogenic) variants in <i>ABCC6</i> by molecular genetic testing (see <a href="/books/NBK1113/table/pxe.T.molecular_genetic_testing_used_in/?report=objectonly" target="object" rid-ob="figobpxeTmoleculargenetictestingusedin">Table 1</a>).</p><p>Note: (1) Per ACMG/AMP variant interpretation guidelines, the terms "pathogenic variants" and "likely pathogenic variants" are synonymous in a clinical setting, meaning that both are considered diagnostic and both can be used for clinical decision making [<a class="bibr" href="#pxe.REF.richards.2015.405" rid="pxe.REF.richards.2015.405">Richards et al 2015</a>]. Reference to "pathogenic variants" in this section is understood to include any likely pathogenic variants. (2) Identification of biallelic <i>ABCC6</i> variants of uncertain significance (or of one known <i>ABCC6</i> pathogenic variant and one <i>ABCC6</i> variant of uncertain significance) does not establish or rule out the diagnosis.</p><div id="pxe.Clinical_Diagnosis"><h4>Clinical Diagnosis</h4><p>The diagnosis of PXE is established in an individual with characteristic skin lesions on the neck, axillae, and/or antecubital fosse and at least one characteristic retinal finding (<i>peau d'orange</i>, angioid streaks, or choroidal vascularization). When eye findings are characteristic but skin findings are equivocal or subtle, identification of calcified dystrophic elastic fibers using a von Kossa or similar stain on a biopsy of potentially lesional skin establishes the diagnosis.</p></div><div id="pxe.Molecular_Diagnosis"><h4>Molecular Diagnosis</h4><p>Molecular genetic testing approaches can include a combination of <b>gene-targeted testing</b> (single-gene testing, multigene panel) and <b>comprehensive</b>
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<b>genomic testing</b> (exome sequencing, exome array, genome sequencing) depending on the phenotype.</p><p>Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Individuals with the distinctive findings described in <a href="#pxe.Suggestive_Findings">Suggestive Findings</a> are likely to be diagnosed using gene-targeted testing (see <b>Option 1</b>), whereas those in whom the diagnosis of PXE has not been considered are more likely to be diagnosed using genomic testing (see <b>Option 2</b>).</p><p>
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<b>Option 1</b>
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</p><ul><li class="half_rhythm"><div class="half_rhythm"><b>Single-gene testing.</b> Sequence analysis of <i>ABCC6</i> detects small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. Sequence analysis is performed first; if only one or no pathogenic variant is found, gene-targeted deletion/duplication analysis is performed to detect intragenic deletions or duplications.</div><div class="half_rhythm">Note: (1) Presence of the pseudogenes <i>ABCC6P1</i> (which has high homology to exons1-9) and <i>ABCC6P2</i> (high homology to exons 1-4) interferes with both sequence analysis and deletion/duplication analysis. (2) Multiplex ligation-dependent probe amplification (MLPA) analysis to detect intragenic deletions or duplications using a widely available commercial kit does not include probes for exons 1, 3, 6, 16, 19-20, 29, and 31. Therefore, deletion or duplications confined to these exons cannot be detected by this assay. This technical challenge likely contributes to the disease alleles not detected in affected individuals (see <a href="/books/NBK1113/table/pxe.T.molecular_genetic_testing_used_in/?report=objectonly" target="object" rid-ob="figobpxeTmoleculargenetictestingusedin">Table 1</a>).(3) Targeted testing for the most common pathogenic variants may be performed first (see <a href="/books/NBK1113/table/pxe.T.notable_abcc6_pathogenic_variants/?report=objectonly" target="object" rid-ob="figobpxeTnotableabcc6pathogenicvariants">Table 7</a>).</div></li><li class="half_rhythm"><div class="half_rhythm"><b>A multigene panel</b> that includes <i>ABCC6</i> and other genes of interest (see <a href="#pxe.Differential_Diagnosis">Differential Diagnosis</a>) is most likely to identify the genetic cause of the condition while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this <i>GeneReview</i>. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For this disorder a multigene panel that also includes deletion/duplication analysis is recommended (see <a href="/books/NBK1113/table/pxe.T.molecular_genetic_testing_used_in/?report=objectonly" target="object" rid-ob="figobpxeTmoleculargenetictestingusedin">Table 1</a>).</div><div class="half_rhythm">For an introduction to multigene panels click <a href="/books/n/gene/app5/?report=reader#app5.Multigene_Panels">here</a>. More detailed information for clinicians ordering genetic tests can be found <a href="/books/n/gene/app5/?report=reader#app5.Multigene_Panels_FAQs">here</a>.</div></li></ul><p>
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<b>Option 2</b>
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</p><p><b>Comprehensive genomic testing.</b> When the diagnosis of PXE has not been considered, comprehensive genomic testing (which does not require the clinician to determine which gene[s] are likely involved) is often an option. <b>Exome sequencing</b> is the most commonly used genomic testing method; <b>genome sequencing</b> is also possible.</p><p>If exome sequencing is not diagnostic, <b>exome array</b> (when clinically available) may be considered to detect (multi)exon deletions or duplications that cannot be detected by sequence analysis.</p><p>For an introduction to comprehensive genomic testing click <a href="/books/n/gene/app5/?report=reader#app5.Comprehensive_Genomic_Testing">here</a>. More detailed information for clinicians ordering genomic testing can be found <a href="/books/n/gene/app5/?report=reader#app5.Comprehensive_Genomic_Testing_1">here</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figpxeTmoleculargenetictestingusedin"><a href="/books/NBK1113/table/pxe.T.molecular_genetic_testing_used_in/?report=objectonly" target="object" title="Table 1. " class="img_link icnblk_img" rid-ob="figobpxeTmoleculargenetictestingusedin"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="pxe.T.molecular_genetic_testing_used_in"><a href="/books/NBK1113/table/pxe.T.molecular_genetic_testing_used_in/?report=objectonly" target="object" rid-ob="figobpxeTmoleculargenetictestingusedin">Table 1. </a></h4><p class="float-caption no_bottom_margin">Molecular Genetic Testing Used in Pseudoxanthoma Elasticum (PXE) </p></div></div></div></div></div><div id="pxe.Clinical_Characteristics"><h2 id="_pxe_Clinical_Characteristics_">Clinical Characteristics</h2><div id="pxe.Clinical_Description"><h3>Clinical Description</h3><p>Pseudoxanthoma elasticum (PXE) is a systemic disorder that affects the elastic tissue of the skin, the eye, and the cardiovascular and gastrointestinal systems. Individuals can present as early as age five years with papules in the skin and/or between ages ten and 30 years with angioid streaks of the retina found on routine eye examination or associated with retinal hemorrhage. Manifestations of other vascular involvement include gastrointestinal angina and/or bleeding, intermittent claudication of arm and leg muscles, stroke, and renovascular hypertension, especially at an unexpectedly young age.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figpxeTselectfeaturesofpseudoxanthoma"><a href="/books/NBK1113/table/pxe.T.select_features_of_pseudoxanthoma/?report=objectonly" target="object" title="Table 2. " class="img_link icnblk_img" rid-ob="figobpxeTselectfeaturesofpseudoxanthoma"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="pxe.T.select_features_of_pseudoxanthoma"><a href="/books/NBK1113/table/pxe.T.select_features_of_pseudoxanthoma/?report=objectonly" target="object" rid-ob="figobpxeTselectfeaturesofpseudoxanthoma">Table 2. </a></h4><p class="float-caption no_bottom_margin">Select Features of Pseudoxanthoma Elasticum (PXE) </p></div></div><p><b>Skin.</b> Skin lesions are generally the first sign and are present between the first and second decade of life, but are often not recognized as a sign of PXE. The primary skin lesion is a papule that is somewhat darker than the person's natural skin tone, i.e., yellowish on white skin, black on brown skin, usually seen on the lateral aspect of the neck or the flexural creases (e.g., the antecubital fossae, axillae, groin, or popliteal fossae). Occasionally, there is periumbilical involvement.</p><p>The papules gradually coalesce to form plaques, and eventually the skin, especially of the neck, axilla, and groin, becomes loose, lax, and redundant.</p><p>Mucous membranes can show similar yellowish lesions, most commonly the inner aspect of the lower lip and the vaginal mucosa.</p><p><b>Eye.</b> The earliest ocular finding is a diffuse mottling of the fundus known as <i>peau d'orange</i>, generally appearing between adolescence and the late second decade.</p><p>In nearly every person with PXE, angioid streaks develop between the first and second decade.</p><p>Neither angioid streaks nor <i>peau d'orange</i> affects visual acuity; however, spontaneous subretinal neovascularization and hemorrhage can occur and lead to visual distortion (metamorphopsia) and decreased visual acuity, resulting in disciform scarring and, when the macula or fovea is involved, permanent loss of central vision. In some cases, atrophy similar to geographic atrophy in age-related macular degeneration develops and can be the cause of vision loss [<a class="bibr" href="#pxe.REF.gliem.2016.3323" rid="pxe.REF.gliem.2016.3323">Gliem et al 2016</a>, <a class="bibr" href="#pxe.REF.risseeuw.2019.1580" rid="pxe.REF.risseeuw.2019.1580">Risseeuw et al 2019</a>].</p><p><b>Gastrointestinal.</b> The most common site of bleeding is the upper gastrointestinal tract, particularly the stomach. The cause of bleeding is not well understood; one theory is that it may begin with superficial bleeding from erosive gastritis, then becomes massive and uncontrolled due to defective vasoconstriction of affected arteries. Diffuse punctate bleeding and erosions can be seen on gastroscopy, but an exact source of the hemorrhage may be difficult to locate.</p><p><b>Vascular.</b> Mineralization of the internal elastic lamina of medium-sized arteries, predominantly in peripheral arteries (arms, legs) and intracranial internal carotid arteries, resulting in arterial narrowing occurs frequently in PXE. Arterial narrowing can lead to asymmetric or diminished pulses in the limbs and, if severe enough, can cause intermittent claudication of the leg and arm muscles, small strokes (cerebrovascular arteries), intestinal angina (celiac or mesenteric arteries), and renovascular hypertension (renal arteries).</p><p>Although one small series suggested an increased incidence of mitral valve prolapse in individuals with PXE [<a class="bibr" href="#pxe.REF.lebwohl.1982.228" rid="pxe.REF.lebwohl.1982.228">Lebwohl et al 1982</a>], this has never been replicated.</p></div><div id="pxe.GenotypePhenotype_Correlations"><h3>Genotype-Phenotype Correlations</h3><p>No genotype-phenotype correlations for <i>ABCC6</i> have been identified.</p><p>In addition, the phenotype does not differ between individuals with biallelic <i>ABCC6</i> pathogenic variants and those who meet clinical diagnostic criteria but who do not have a known genetic cause.</p></div><div id="pxe.Nomenclature"><h3>Nomenclature</h3><p>Earlier reports sometimes referred to PXE as Gröndblad-Strandberg syndrome.</p></div><div id="pxe.Prevalence"><h3>Prevalence</h3><p>Prevalence data are not available.</p><p>Common disease-associated variants have been identified in individuals of European descent [<a class="bibr" href="#pxe.REF.pfendner.2007.621" rid="pxe.REF.pfendner.2007.621">Pfendner et al 2007</a>, <a class="bibr" href="#pxe.REF.legrand.2017.909" rid="pxe.REF.legrand.2017.909">Legrand et al 2017</a>] and in Japanese populations [<a class="bibr" href="#pxe.REF.iwanaga.2017.644" rid="pxe.REF.iwanaga.2017.644">Iwanaga et al 2017</a>]. A founder variant was also identified in the Afrikaner population [<a class="bibr" href="#pxe.REF.le_saux.2002.331" rid="pxe.REF.le_saux.2002.331">Le Saux et al 2002</a>]. See <a href="/books/NBK1113/table/pxe.T.notable_abcc6_pathogenic_variants/?report=objectonly" target="object" rid-ob="figobpxeTnotableabcc6pathogenicvariants">Table 7</a> for details about notable variants.</p></div></div><div id="pxe.Genetically_Related_Allelic_Disorder"><h2 id="_pxe_Genetically_Related_Allelic_Disorder_">Genetically Related (Allelic) Disorders</h2><p>A few individuals with <a href="/books/n/gene/gaci/?report=reader">generalized arterial calcification of infancy</a> (GACI) without detectable pathogenic variants in <i>ENPP1</i> have been reported to have biallelic pathogenic variants in <i>ABCC6</i> [<a class="bibr" href="#pxe.REF.nitschke.2012.25" rid="pxe.REF.nitschke.2012.25">Nitschke et al 2012</a>].</p></div><div id="pxe.Differential_Diagnosis"><h2 id="_pxe_Differential_Diagnosis_">Differential Diagnosis</h2><div id="pxe.Hereditary_Disorders"><h3>Hereditary Disorders</h3><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figpxeTgenesofinterestinthedifferent"><a href="/books/NBK1113/table/pxe.T.genes_of_interest_in_the_different/?report=objectonly" target="object" title="Table 3. " class="img_link icnblk_img" rid-ob="figobpxeTgenesofinterestinthedifferent"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="pxe.T.genes_of_interest_in_the_different"><a href="/books/NBK1113/table/pxe.T.genes_of_interest_in_the_different/?report=objectonly" target="object" rid-ob="figobpxeTgenesofinterestinthedifferent">Table 3. </a></h4><p class="float-caption no_bottom_margin">Genes of Interest in the Differential Diagnosis of Pseudoxanthoma Elasticum (PXE) </p></div></div></div><div id="pxe.Acquired_Disorders_and_Disorders_wit"><h3>Acquired Disorders and Disorders without a Known Genetic Cause</h3><div id="pxe.Skin"><h4>Skin</h4><p>The skin lesions of pseudoxanthoma elasticum (PXE) are mimicked by those in the following acquired conditions:</p><ul><li class="half_rhythm"><div>White fibrous papulosis of the neck and papillary dermal elastolysis, both signs of intrinsic aging, associated with thinning or loss of elastic fibers and focal thickening of the collagen fiber network (collectively known as fibroelastolytic papulosis)</div></li><li class="half_rhythm"><div>Solar elastosis, in which yellowish-white papules occur in the skin of the neck and chest as a result of photoaging</div></li><li class="half_rhythm"><div>Late-onset focal dermal elastosis</div></li></ul><p>Long-term D-penicillamine treatment (used in the treatment of <a href="/books/n/gene/wilson/?report=reader">Wilson disease</a> and prevention of cysteine kidney stones in cystinuria results in skin lesions that clinically resemble PXE but do not exhibit elastic fiber mineralization histologically [<a class="bibr" href="#pxe.REF.b_cuwe.2005.60" rid="pxe.REF.b_cuwe.2005.60">Bécuwe et al 2005</a>].</p></div><div id="pxe.Eyes"><h4>Eyes</h4><p>In high myopia, lacquer cracks may resemble angioid streaks.</p><p>Subretinal neovascularization with hemorrhage can be seen in the absence of angioid streaks in age-related macular degeneration, high myopia, and presumed ocular histoplasmosis. Macular atrophy can also be seen in age-related macular degeneration.</p></div><div id="pxe.Recurrent_Gastrointestinal_Bleeding"><h4>Recurrent Gastrointestinal Bleeding</h4><p>PXE should be considered in the differential diagnosis of recurrent gastrointestinal bleeding of unknown cause [<a class="bibr" href="#pxe.REF.dalle.2002.213" rid="pxe.REF.dalle.2002.213">Dalle & Geboes 2002</a>].</p></div></div></div><div id="pxe.Management"><h2 id="_pxe_Management_">Management</h2><div id="pxe.Evaluations_Following_Initial_Diagno"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and needs in an individual diagnosed with pseudoxanthoma elasticum (PXE), the evaluations summarized in <a href="/books/NBK1113/table/pxe.T.recommended_evaluations_following/?report=objectonly" target="object" rid-ob="figobpxeTrecommendedevaluationsfollowing">Table 4</a> (if not performed as part of the evaluation that led to the diagnosis) are recommended.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figpxeTrecommendedevaluationsfollowing"><a href="/books/NBK1113/table/pxe.T.recommended_evaluations_following/?report=objectonly" target="object" title="Table 4. " class="img_link icnblk_img" rid-ob="figobpxeTrecommendedevaluationsfollowing"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="pxe.T.recommended_evaluations_following"><a href="/books/NBK1113/table/pxe.T.recommended_evaluations_following/?report=objectonly" target="object" rid-ob="figobpxeTrecommendedevaluationsfollowing">Table 4. </a></h4><p class="float-caption no_bottom_margin">Recommended Evaluations Following Initial Diagnosis in Individuals with Pseudoxanthoma Elasticum (PXE) </p></div></div></div><div id="pxe.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><p>No specific treatment for PXE exists.</p><p>Management of PXE requires coordinated input from multidisciplinary specialists (see <a href="/books/NBK1113/table/pxe.T.treatment_of_manifestations_in_ind/?report=objectonly" target="object" rid-ob="figobpxeTtreatmentofmanifestationsinind">Table 5</a>). Support groups can benefit affected individuals and their families by providing accurate information and education and reducing isolation.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figpxeTtreatmentofmanifestationsinind"><a href="/books/NBK1113/table/pxe.T.treatment_of_manifestations_in_ind/?report=objectonly" target="object" title="Table 5. " class="img_link icnblk_img" rid-ob="figobpxeTtreatmentofmanifestationsinind"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="pxe.T.treatment_of_manifestations_in_ind"><a href="/books/NBK1113/table/pxe.T.treatment_of_manifestations_in_ind/?report=objectonly" target="object" rid-ob="figobpxeTtreatmentofmanifestationsinind">Table 5. </a></h4><p class="float-caption no_bottom_margin">Treatment of Manifestations in Individuals with Pseudoxanthoma Elasticum (PXE) </p></div></div></div><div id="pxe.Surveillance"><h3>Surveillance</h3><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figpxeTrecommendedsurveillanceforindiv"><a href="/books/NBK1113/table/pxe.T.recommended_surveillance_for_indiv/?report=objectonly" target="object" title="Table 6. " class="img_link icnblk_img" rid-ob="figobpxeTrecommendedsurveillanceforindiv"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="pxe.T.recommended_surveillance_for_indiv"><a href="/books/NBK1113/table/pxe.T.recommended_surveillance_for_indiv/?report=objectonly" target="object" rid-ob="figobpxeTrecommendedsurveillanceforindiv">Table 6. </a></h4><p class="float-caption no_bottom_margin">Recommended Surveillance for Individuals with Pseudoxanthoma Elasticum (PXE) </p></div></div></div><div id="pxe.AgentsCircumstances_to_Avoid"><h3>Agents/Circumstances to Avoid</h3><p>Racquet and contact sports carry an increased risk for ocular and head trauma, both of which have been reported to precipitate retinal hemorrhage in patients with angioid streaks; participation in such activities should be discouraged.</p><p>Individuals with PXE who participate in sports and physical recreation should wear appropriate protective eyewear such as polycarbonate sports goggles and/or protective helmets with eye shields.</p><p>Aspirin and nonsteroidal anti-inflammatory medications should be avoided whenever possible to reduce the risk of gastrointestinal bleeding.</p><p>Smoking is strongly discouraged because of its vasoconstrictive properties.</p></div><div id="pxe.Evaluation_of_Relatives_at_Risk"><h3>Evaluation of Relatives at Risk</h3><p>It is appropriate to clarify the genetic status of apparently asymptomatic older and younger at-risk sibs of an affected individual in order to identify as early as possible those who would benefit from prompt initiation of medical management and preventive measures. In those without a molecular diagnosis, at-risk sibs should be screened by clinical examination, medical history, and detailed review of cardiovascular systems. Evaluations can include:</p><ul><li class="half_rhythm"><div>Retinal examination for <i>peau d'orange</i> and angioid streaks, which are usually evident by the first or second decade, and skin examination for characteristic skin lesions if the pathogenic variants in the family are not known;</div></li><li class="half_rhythm"><div>Molecular genetic testing if the <i>ABCC6</i> pathogenic variants in the family are known.</div></li></ul><p>See <a href="#pxe.Related_Genetic_Counseling_Issues">Genetic Counseling</a> for issues related to testing of at-risk relatives for genetic counseling purposes.</p></div><div id="pxe.Pregnancy_Management"><h3>Pregnancy Management</h3><p>Most women with PXE have normal pregnancies; PXE is not associated with markedly increased fetal loss or adverse reproductive outcomes. The incidence of gastrointestinal bleeding and retinal complications (<1%) is lower than previously thought [<a class="bibr" href="#pxe.REF.bercovitch.2004.1011" rid="pxe.REF.bercovitch.2004.1011">Bercovitch et al 2004</a>]. Retinal examination during pregnancy and prompt attention to any visual symptoms are advised. Vaginal delivery appears safe for the retina of women with PXE if no active choroidal neovascularization is present. Angioid streaks alone are not an indication for medical interventions during delivery.</p><p>In the series of 795 pregnancies examined by <a class="bibr" href="#pxe.REF.bercovitch.2004.1011" rid="pxe.REF.bercovitch.2004.1011">Bercovitch et al [2004]</a>, a history of pregnancy did not have a statistically significant effect on the severity of manifestations of PXE in women older than age 40 years. This was confirmed in a 2016 review of the literature [<a class="bibr" href="#pxe.REF.camacho.2016.1061" rid="pxe.REF.camacho.2016.1061">Camacho et al 2016</a>].</p></div><div id="pxe.Therapies_Under_Investigation"><h3>Therapies Under Investigation</h3><p>Search <a href="https://clinicaltrials.gov/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ClinicalTrials.gov</a> in the US and <a href="https://www.clinicaltrialsregister.eu/ctr-search/search" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">EU Clinical Trials Register</a> in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.</p></div></div><div id="pxe.Genetic_Counseling"><h2 id="_pxe_Genetic_Counseling_">Genetic Counseling</h2><p>
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<i>Genetic counseling is the process of providing individuals and families with
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information on the nature, mode(s) of inheritance, and implications of genetic disorders to help them
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make informed medical and personal decisions. The following section deals with genetic
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risk assessment and the use of family history and genetic testing to clarify genetic
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status for family members; it is not meant to address all personal, cultural, or
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ethical issues that may arise or to substitute for consultation with a genetics
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professional</i>. —ED.</p><div id="pxe.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p>Pseudoxanthoma elasticum (PXE) is inherited in an autosomal recessive manner.</p><p>Note: Pseudodominant inheritance (i.e., an autosomal recessive condition present in individuals in two or more generations) is reported in some families [<a class="bibr" href="#pxe.REF.bergen.2006.704" rid="pxe.REF.bergen.2006.704">Bergen 2006</a>, <a class="bibr" href="#pxe.REF.ringpfeil.2006.782" rid="pxe.REF.ringpfeil.2006.782">Ringpfeil et al 2006</a>, <a class="bibr" href="#pxe.REF.legrand.2017.909" rid="pxe.REF.legrand.2017.909">Legrand et al 2017</a>].</p></div><div id="pxe.Risk_to_Family_Members"><h3>Risk to Family Members</h3><p>
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<b>Parents of a proband</b>
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</p><ul><li class="half_rhythm"><div>If the parents of a proband are clinically unaffected, they are obligate heterozygotes (i.e., presumed to be carriers of one <i>ABCC6</i> pathogenic variant based on family history).</div></li><li class="half_rhythm"><div>In populations with a high carrier rate and/or a high rate of consanguinity, it is possible that affected children will be born to an affected individual and a carrier (or even to two affected individuals) resulting in pseudodominant inheritance.</div></li><li class="half_rhythm"><div>In very rare instances, only one parent is a carrier and the proband has PXE as the result of one inherited <i>ABCC6</i> pathogenic variant and one <i>de novo</i>
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<i>ABCC6</i> pathogenic variant [<a class="bibr" href="#pxe.REF.legrand.2017.909" rid="pxe.REF.legrand.2017.909">Legrand et al 2017</a>].</div></li><li class="half_rhythm"><div>Molecular genetic testing is recommended for the parents of a proband to confirm that each parent is heterozygous for an <i>ABCC6</i> pathogenic variant and to allow reliable recurrence risk assessment.</div></li><li class="half_rhythm"><div>Heterozygotes (carriers) are asymptomatic and are not at risk of developing the disorder.</div></li></ul><p>
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<b>Sibs of a proband</b>
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</p><ul><li class="half_rhythm"><div>If both parents are known to be heterozygous for an <i>ABCC6</i> pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.</div></li><li class="half_rhythm"><div>Intrafamilial clinical variability in PXE is observed; thus, sibs who inherit biallelic <i>ABCC6</i> pathogenic variants may be more or less severely affected than the proband.</div></li><li class="half_rhythm"><div>Heterozygotes (carriers) are asymptomatic and are not at risk of developing the disorder.</div></li></ul><p>
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<b>Offspring of a proband</b>
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</p><ul><li class="half_rhythm"><div>Unless an affected individual's reproductive partner also has PXE or is a carrier, offspring will be obligate heterozygotes (carriers) for a pathogenic variant in <i>ABCC6</i>.</div></li><li class="half_rhythm"><div>In populations with a high carrier rate and/or a high rate of consanguinity, the reproductive partner of the proband may have two <i>ABCC6</i> pathogenic variants or be heterozygous. Thus, the risk to offspring is most accurately determined after molecular genetic testing of the proband's reproductive partner.</div></li></ul><p><b>Other family members.</b> If both parents of the proband are known to be heterozygous for an <i>ABCC6</i> pathogenic variant, each sib of the proband's parents is at a 50% risk of being a carrier of a pathogenic variant.</p></div><div id="pxe.Carrier_Detection"><h3>Carrier Detection</h3><p>Carrier testing for at-risk relatives requires prior identification of the <i>ABCC6</i> pathogenic variants in the family.</p></div><div id="pxe.Related_Genetic_Counseling_Issues"><h3>Related Genetic Counseling Issues</h3><p>See Management, <a href="#pxe.Evaluation_of_Relatives_at_Risk">Evaluation of Relatives at Risk</a> for information on evaluating at-risk relatives for the purpose of early diagnosis and treatment.</p><p>
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<b>Family planning</b>
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</p><ul><li class="half_rhythm"><div>The optimal time for clarification of genetic status, determination of genetic risk, and discussion of the availability of prenatal/preimplantation genetic testing is before pregnancy.</div></li><li class="half_rhythm"><div>It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected, are carriers, or are at risk of being carriers.</div></li></ul><p><b>DNA banking.</b> Because it is likely that testing methodology and our understanding of genes, pathogenic mechanisms, and diseases will improve in the future, consideration should be given to banking DNA from probands in whom a molecular diagnosis has not been confirmed (i.e., the causative pathogenic mechanism is unknown). For more information, see <a class="bibr" href="#pxe.REF.huang.2022.389" rid="pxe.REF.huang.2022.389">Huang et al [2022]</a>.</p></div><div id="pxe.Prenatal_Testing_and_Preimplantation"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once the <i>ABCC6</i> pathogenic variants have been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible.</p><p>Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing, particularly if the testing is being considered for the purpose of pregnancy termination rather than early confirmation or exclusion of the diagnosis. While most centers would consider use of prenatal testing to be a personal decision, discussion of these issues may be helpful.</p></div></div><div id="pxe.Resources"><h2 id="_pxe_Resources_">Resources</h2><p>
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<i>GeneReviews staff has selected the following disease-specific and/or umbrella
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support organizations and/or registries for the benefit of individuals with this disorder
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and their families. GeneReviews is not responsible for the information provided by other
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organizations. For information on selection criteria, click <a href="/books/n/gene/app4/?report=reader">here</a>.</i></p>
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<ul><li class="half_rhythm"><div>
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<b>MedlinePlus</b>
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</div><div>
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<a href="https://medlineplus.gov/genetics/condition/pseudoxanthoma-elasticum/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Pseudoxanthoma elasticum</a>
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</div></li><li class="half_rhythm"><div>
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<b>PXE International, Inc.</b>
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</div><div>4301 Connecticut Avenue, NW</div><div>Suite 404</div><div>Washington DC 20008-2369</div><div><b>Phone:</b> 202-362-9599</div><div><b>Fax:</b> 202-966-8553</div><div><b>Email:</b> info@pxe.org</div><div>
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<a href="https://www.pxe.org/index.php/what-is-pseudoxanthoma-elasticum" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.pxe.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>PXE International BioBank and Clinical Data Registry</b>
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</div><div>
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<a href="https://www.pxe.org/node/104" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.pxe.org</a>
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</div></li></ul>
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</div><div id="pxe.Molecular_Genetics"><h2 id="_pxe_Molecular_Genetics_">Molecular Genetics</h2><p><i>Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —</i>ED.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figpxemolgenTA"><a href="/books/NBK1113/table/pxe.molgen.TA/?report=objectonly" target="object" title="Table A." class="img_link icnblk_img" rid-ob="figobpxemolgenTA"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="pxe.molgen.TA"><a href="/books/NBK1113/table/pxe.molgen.TA/?report=objectonly" target="object" rid-ob="figobpxemolgenTA">Table A.</a></h4><p class="float-caption no_bottom_margin">Pseudoxanthoma Elasticum: Genes and Databases </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figpxemolgenTB"><a href="/books/NBK1113/table/pxe.molgen.TB/?report=objectonly" target="object" title="Table B." class="img_link icnblk_img" rid-ob="figobpxemolgenTB"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="pxe.molgen.TB"><a href="/books/NBK1113/table/pxe.molgen.TB/?report=objectonly" target="object" rid-ob="figobpxemolgenTB">Table B.</a></h4><p class="float-caption no_bottom_margin">OMIM Entries for Pseudoxanthoma Elasticum (View All in OMIM) </p></div></div><div id="pxe.Molecular_Pathogenesis"><h3>Molecular Pathogenesis</h3><p><i>ABCC6</i> encodes multidrug resistance-associated protein 6 (also known as ATP-binding cassette sub-family C member 6, ABCC6). Although the mechanism of action is not completely understood, there is evidence that disease-associated low levels of inorganic pyrophosphate in the blood cause mineralization in peripheral tissue.</p><p><b>Mechanism of disease causation.</b> Loss of ABCC6 function causes the disease.</p><p><b><i>ABCC6</i>-specific laboratory technical considerations.</b> The presence of the two following pseudogenes interferes with both sequence analysis and deletion/duplication analysis:</p><ul><li class="half_rhythm"><div><i>ABCC6P1</i>, which has high homology to exons 1-9</div></li><li class="half_rhythm"><div><i>ABCC6P2</i>, which has high homology to exons 1-4</div></li></ul><p>Multiplex ligation-dependent probe amplification (MLPA) analysis to detect intragenic deletions or duplications using a widely available commercial kit does not include probes for exons 1, 3, 6, 16, 19-20, 29, and 31. Therefore, deletion or duplications confined to these exons cannot be detected by this assay. This technical challenge likely contributes to the disease alleles not detected in affected individuals (see <a href="/books/NBK1113/table/pxe.T.molecular_genetic_testing_used_in/?report=objectonly" target="object" rid-ob="figobpxeTmoleculargenetictestingusedin">Table 1</a>).</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figpxeTnotableabcc6pathogenicvariants"><a href="/books/NBK1113/table/pxe.T.notable_abcc6_pathogenic_variants/?report=objectonly" target="object" title="Table 7. " class="img_link icnblk_img" rid-ob="figobpxeTnotableabcc6pathogenicvariants"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="pxe.T.notable_abcc6_pathogenic_variants"><a href="/books/NBK1113/table/pxe.T.notable_abcc6_pathogenic_variants/?report=objectonly" target="object" rid-ob="figobpxeTnotableabcc6pathogenicvariants">Table 7. </a></h4><p class="float-caption no_bottom_margin">Notable <i>ABCC6</i> Pathogenic Variants </p></div></div></div></div><div id="pxe.Chapter_Notes"><h2 id="_pxe_Chapter_Notes_">Chapter Notes</h2><div id="pxe.Author_Notes"><h3>Author Notes</h3><p>Sharon F Terry, MA, is the co-founder of PXE International and co-investigator on more than 30 PXE clinical studies. Her publications exceed 170 peer-reviewed papers. She has given more than 500 presentations at national and international meetings. She manages the International PXE Research Consortium. She is the founder of the PXE BioBank and Registry. She is also the president and CEO of Genetic Alliance.</p><p>Dr Jouni Uitto is internationally recognized for his research on connective tissue biochemistry and molecular biology in relation to cutaneous diseases. Dr Uitto's publications include 725 original articles in peer-reviewed journals, 352 textbook chapters and review articles, and 1,048 abstracts on presentations at national and international meetings.</p></div><div id="pxe.Author_History"><h3>Author History</h3><p>Jouni Uitto, MD (2020-present)<br />Lionel G Bercovitch, MD; Brown University (2001-2020) <br />Charles D Boyd, PhD; University of Hawaii (2001-2006) <br />Sharon F Terry, MA (2001-present)</p></div><div id="pxe.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>4 June 2020 (bp) Comprehensive update posted live</div></li><li class="half_rhythm"><div>14 June 2012 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>2 April 2007 (st) Revision: Molecular Genetic Testing – targeted mutation analysis changed to deletion analysis</div></li><li class="half_rhythm"><div>11 December 2006 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>5 November 2003 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>14 March 2002 (st) Author revision</div></li><li class="half_rhythm"><div>5 June 2001 (me) Review posted live</div></li><li class="half_rhythm"><div>September 2000 (st) Original submission</div></li></ul></div></div><div id="pxe.References"><h2 id="_pxe_References_">References</h2><div id="pxe.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="pxe.REF.anderson.2013.1425">Anderson JL, Halperin JL, Albert NM, Bozkurt B, Brindis RG, Curtis LH, DeMets D, Guyton RA, Hochman JS, Kovacs RJ, Ohman EM, Pressler SJ, Sellke FW, Shen WK. Management of patients with peripheral artery disease (compilation of 2005 and 2011 ACCF/AHA guideline recommendations): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. <span><span class="ref-journal">Circulation. </span>2013;<span class="ref-vol">127</span>:1425–43.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/23457117" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23457117</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="pxe.REF.battaglia_parodi.2019.273">Battaglia Parodi M, Romano F, Marchese A, Arrigo A, Llorenç V, Cicinelli MV, Bandello F, Adán A. Anti-VEGF treatment for choroidal neovascularization complicating pattern dystrophy-like deposit associated with pseudoxanthoma elasticum. <span><span class="ref-journal">Graefes Arch Clin Exp Ophthalmol. </span>2019;<span class="ref-vol">257</span>:273–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/30470876" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30470876</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="pxe.REF.b_cuwe.2005.60">Bécuwe C, Dalle S, Ronger-Savlé S, Skowron F, Balme B, Kanitakis J, Thomas L. Elastosis perforans serpiginosa associated with pseudo-pseudoxanthoma elasticum during treatment of Wilson's disease with penicillamine. <span><span class="ref-journal">Dermatology. </span>2005;<span class="ref-vol">210</span>:60–3.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15604549" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15604549</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="pxe.REF.bercovitch.2004.1011">Bercovitch L, Leroux T, Terry S, Weinstock MA. Pregnancy and obstetrical outcomes in pseudoxanthoma elasticum. <span><span class="ref-journal">Br J Dermatol. </span>2004;<span class="ref-vol">151</span>:1011–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15541079" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15541079</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="pxe.REF.bergen.2006.704">Bergen AA. Pseudoxanthoma elasticum: the end of the autosomal dominant segregation myth. <span><span class="ref-journal">J Invest Dermatol. </span>2006;<span class="ref-vol">126</span>:704–5.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16541094" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16541094</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="pxe.REF.camacho.2016.1061">Camacho M, Rengel C, López-Herrero E, Carrillo JL, Eslava AJ, Valdivielso P. Approach to the management of pregnancy in patients with pseudoxanthoma elasticum: a review. <span><span class="ref-journal">J Obstet Gynaecol. </span>2016;<span class="ref-vol">36</span>:1061–6.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/27623860" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27623860</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="pxe.REF.chassaing.2007.1046">Chassaing N, Martin L, Bourthoumieu S, Calvas P, Hovnanian A. Contribution of ABCC6 genomic rearrangements to the diagnosis of pseudoxanthoma elasticum in French patients. <span><span class="ref-journal">Hum Mutat. </span>2007;<span class="ref-vol">28</span>:1046.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17823974" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17823974</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="pxe.REF.dalle.2002.213">Dalle I, Geboes K. Vascular lesions of the gastrointestinal tract. <span><span class="ref-journal">Acta Gastroenterol Belg. </span>2002;<span class="ref-vol">65</span>:213–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12619428" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12619428</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="pxe.REF.fihn.2014.1929">Fihn SD, Blankenship JC, Alexander KP, Bittl JA, Byrne JG, Fletcher BJ, Fonarow GC, Lange RA, Levine GN, Maddox TM, Naidu SS, Ohman EM, Smith PK. 2014 ACC/AHA/AATS/PCNA/SCAI/STS focused update of the guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines, and the American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. <span><span class="ref-journal">J Am Coll Cardiol. </span>2014;<span class="ref-vol">64</span>:1929–49.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/25077860" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25077860</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="pxe.REF.fihn.2012.e44">Fihn SD, Gardin JM, Abrams J, Berra K, Blankenship JC, Dallas AP, Douglas PS, Foody JM, Gerber TC, Hinderliter AL, King SB 3rd, Kligfield PD, Krumholz HM, Kwong RY, Lim MJ, Linderbaum JA, Mack MJ, Munger MA, Prager RL, Sabik JF, Shaw LJ, Sikkema JD, Smith CR Jr, Smith SC Jr, Spertus JA, Williams SV, et al. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. <span><span class="ref-journal">J Am Coll Cardiol. </span>2012;<span class="ref-vol">60</span>:e44–e164.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/23182125" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23182125</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="pxe.REF.gliem.2016.3323">Gliem M, Müller PL, Birtel J, Hendig D, Holz FG, Charbel Issa P. Frequency, phenotypic characteristics and progression of atrophy associated with a diseased Bruch's membrane in pseudoxanthoma elasticum. <span><span class="ref-journal">Invest Ophthalmol Vis Sci. </span>2016;<span class="ref-vol">57</span>:3323–30.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/27367499" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27367499</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="pxe.REF.huang.2022.389">Huang SJ, Amendola LM, Sternen DL. Variation among DNA banking consent forms: points for clinicians to bank on. <span><span class="ref-journal">J Community Genet. </span>2022;<span class="ref-vol">13</span>:389–97.</span> [<a href="/pmc/articles/PMC9314484/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC9314484</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/35834113" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 35834113</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="pxe.REF.iwanaga.2017.644">Iwanaga A, Okubo Y, Yozaki M, Koike Y, Kuwatsuka Y, Tomimura S, Yamamoto Y, Tamura H, Ikeda S, Maemura K, Tsuiki E, Kitaoka T, Endo Y, Mishima H, Yoshiura KI, Ogi T, Tanizaki H, Wataya-Kaneda M, Hattori T, Utani A. Analysis of clinical symptoms and ABCC6 mutations in 76 Japanese patients with pseudoxanthoma elasticum. <span><span class="ref-journal">J Dermatol. </span>2017;<span class="ref-vol">44</span>:644–50.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/28186352" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28186352</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="pxe.REF.kringen.2015.233">Kringen MK, Stormo C, Berg JP, Terry SF, Vocke CM, Rizvi S, Hendig D, Piehler AP. Copy number variation in the ATP-binding cassette transporter ABCC6 gene and ABCC6 pseudogenes in patients with pseudoxanthoma elasticum. <span><span class="ref-journal">Mol Genet Genomic Med. </span>2015;<span class="ref-vol">3</span>:233–7.</span> [<a href="/pmc/articles/PMC4444165/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4444165</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26029710" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26029710</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="pxe.REF.lebwohl.1982.228">Lebwohl MG, Distefano D, Prioleau PG, Uram M, Yannuzzi LA, Fleischmajer R. Pseudoxanthoma elasticum and mitral-valve prolapse. <span><span class="ref-journal">N Engl J Med. </span>1982;<span class="ref-vol">307</span>:228–31.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/7088072" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7088072</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="pxe.REF.legrand.2017.909">Legrand A, Cornez L, Samkari W, Mazzella JM, Venisse A, Boccio V, Auribault K, Keren B, Benistan K, Germain DP, Frank M, Jeunemaitre X, Albuisson J. Mutation spectrum in the ABCC6 gene and genotype-phenotype correlations in a French cohort with pseudoxanthoma elasticum. <span><span class="ref-journal">Genet Med. </span>2017;<span class="ref-vol">19</span>:909–17.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/28102862" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28102862</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="pxe.REF.le_saux.2002.331">Le Saux O, Beck K, Sachsinger C, Treiber C, Göring HH, Curry K, Johnson EW, Bercovitch L, Marais AS, Terry SF, Viljoen DL, Boyd CD. Evidence for a founder effect for pseudoxanthoma elasticum in the Afrikaner population of South Africa. <span><span class="ref-journal">Hum Genet. </span>2002;<span class="ref-vol">111</span>:331–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12384774" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12384774</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="pxe.REF.miksch.2005.235">Miksch S, Lumsden A, Guenther UP, Foernzler D, Christen-Zäch S, Daugherty C, Ramesar RK, Lebwohl M, Hohl D, Neldner KH, Lindpaintner K, Richards RI, Struk B. Molecular genetics of pseudoxanthoma elasticum: type and frequency of mutations in ABCC6. <span><span class="ref-journal">Hum Mutat. </span>2005;<span class="ref-vol">26</span>:235–48.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16086317" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16086317</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="pxe.REF.mimoun.2017.1651">Mimoun G, Ebran JM, Grenet T, Donati A, Cohen SY, Ponthieux A. Ranibizumab for choroidal neovascularization secondary to pseudoxanthoma elasticum: 4-year results from the PIXEL study in France. <span><span class="ref-journal">Graefes Arch Clin Exp Ophthalmol. </span>2017;<span class="ref-vol">255</span>:1651–60.</span> [<a href="/pmc/articles/PMC5541092/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5541092</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28493086" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28493086</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="pxe.REF.nitschke.2012.25">Nitschke Y, Baujat G, Botschen U, Wittkampf T, du Moulin M, Stella J, Le Merrer M, Guest G, Lambot K, Tazarourte-Pinturier MF, Chassaing N, Roche O, Feenstra I, Loechner K, Deshpande C, Garber SJ, Chikarmane R, Steinmann B, Shahinyan T, Martorell L, Davies J, Smith WE, Kahler SG, McCulloch M, Wraige E, Loidi L, Höhne W, Martin L, Hadj-Rabia S, Terkeltaub R, Rutsch F. Generalized arterial calcification of infancy and pseudoxanthoma elasticum can be caused by mutations in either ENPP1 or ABCC6. <span><span class="ref-journal">Am J Hum Genet. </span>2012;<span class="ref-vol">90</span>:25–39.</span> [<a href="/pmc/articles/PMC3257960/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3257960</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22209248" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22209248</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="pxe.REF.pfendner.2007.621">Pfendner EG, Vanakker OM, Terry SF, Vourthis S, McAndrew PE, McClain MR, Fratta S, Marais AS, Hariri S, Coucke PJ, Ramsay M, Viljoen D, Terry PF, De Paepe A, Uitto J, Bercovitch LG. Mutation detection in the ABCC6 gene and genotype-phenotype analysis in a large international case series affected by pseudoxanthoma elasticum. <span><span class="ref-journal">J Med Genet. </span>2007;<span class="ref-vol">44</span>:621–8.</span> [<a href="/pmc/articles/PMC2597973/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2597973</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/17617515" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17617515</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="pxe.REF.richards.2015.405">Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. <span><span class="ref-journal">Genet Med. </span>2015;<span class="ref-vol">17</span>:405–24.</span> [<a href="/pmc/articles/PMC4544753/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4544753</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25741868" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25741868</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="pxe.REF.ringpfeil.2006.782">Ringpfeil F, McGuigan K, Fuchsel L, Kozic H, Larralde M, Lebwohl M, Uitto J. Pseudoxanthoma elasticum is a recessive disease characterized by compound heterozygosity. <span><span class="ref-journal">J Invest Dermatol. </span>2006;<span class="ref-vol">126</span>:782–6.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16410789" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16410789</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="pxe.REF.risseeuw.2019.1580">Risseeuw S, Ossewaarde-van Norel J, Klaver CCW, Colijn JM, Imhof SM, van Leeuwen R. Visual acuity in pseudoxanthoma elasticum. <span><span class="ref-journal">Retina. </span>2019;<span class="ref-vol">39</span>:1580–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/29652691" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29652691</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="pxe.REF.uitto.2014.567">Uitto J, Jiang Q, Varadi A, Bercovitch LG, Terry SF. Pseudoxanthoma elasticum: diagnostic features, classification, and treatment options. <span><span class="ref-journal">Expert Opin Orphan Drugs. </span>2014;<span class="ref-vol">2</span>:567–77.</span> [<a href="/pmc/articles/PMC4219573/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4219573</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25383264" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25383264</span></a>]</div></p></li></ul></div></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK1113_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><div class="contrib half_rhythm"><span itemprop="author">Sharon F Terry</span>, MA<div class="affiliation small">PXE International<br />Washington, DC<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="gro.exp@yrrets" class="oemail">gro.exp@yrrets</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Jouni Uitto</span>, MD, PhD<div class="affiliation small">Thomas Jefferson University<br />Philadelphia, Pennsylvania<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.nosreffej@ottiu.inuoj" class="oemail">ude.nosreffej@ottiu.inuoj</a></div></div></div><h3>Publication History</h3><p class="small">Initial Posting: <span itemprop="datePublished">June 5, 2001</span>; Last Update: <span itemprop="dateModified">June 4, 2020</span>.</p><h3>Copyright</h3><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright</a> © 1993-2025, University of Washington, Seattle. GeneReviews is
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contact: <a href="mailto:dev@null" data-email="ude.wu@tssamda" class="oemail">ude.wu@tssamda</a>.</p></div></div><h3>Publisher</h3><p><a href="http://www.washington.edu" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">University of Washington, Seattle</a>, Seattle (WA)</p><h3>NLM Citation</h3><p>Terry SF, Uitto J. Pseudoxanthoma Elasticum. 2001 Jun 5 [Updated 2020 Jun 4]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. <span class="bk_cite_avail"></span></p></div><div class="small-screen-prev"><a href="/books/n/gene/pha2/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a></div><div class="small-screen-next"><a href="/books/n/gene/pf/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div></article><article data-type="table-wrap" id="figobpxeTmoleculargenetictestingusedin"><div id="pxe.T.molecular_genetic_testing_used_in" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in Pseudoxanthoma Elasticum (PXE)</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1113/table/pxe.T.molecular_genetic_testing_used_in/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__pxe.T.molecular_genetic_testing_used_in_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_pxe.T.molecular_genetic_testing_used_in_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene <sup>1</sup></th><th id="hd_h_pxe.T.molecular_genetic_testing_used_in_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Method</th><th id="hd_h_pxe.T.molecular_genetic_testing_used_in_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Proportion of Pathogenic Variants <sup>2</sup> Detectable by Method</th></tr></thead><tbody><tr><td headers="hd_h_pxe.T.molecular_genetic_testing_used_in_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ABCC6</i>
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</td><td headers="hd_h_pxe.T.molecular_genetic_testing_used_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup></td><td headers="hd_h_pxe.T.molecular_genetic_testing_used_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~75%-86% <sup>4</sup></td></tr><tr><td headers="hd_h_pxe.T.molecular_genetic_testing_used_in_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Gene-targeted deletion/duplication analysis <sup>5, 6</sup></td><td headers="hd_h_pxe.T.molecular_genetic_testing_used_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~10%-13% <sup>4, 7</sup></td></tr><tr><td headers="hd_h_pxe.T.molecular_genetic_testing_used_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Unknown</td><td headers="hd_h_pxe.T.molecular_genetic_testing_used_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">NA</td><td headers="hd_h_pxe.T.molecular_genetic_testing_used_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~4%-12%</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="pxe.TF.1.1"><p class="no_margin">See <a href="/books/NBK1113/?report=reader#pxe.molgen.TA">Table A. Genes and Databases</a> for chromosome locus and protein.</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="pxe.TF.1.2"><p class="no_margin">See <a href="#pxe.Molecular_Genetics">Molecular Genetics</a> for information on allelic variants detected in this gene.</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="pxe.TF.1.3"><p class="no_margin">Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click <a href="/books/n/gene/app2/?report=reader">here</a>.</p></div></dd></dl><dl class="bkr_refwrap"><dt>4. </dt><dd><div id="pxe.TF.1.4"><p class="no_margin"><a class="bibr" href="#pxe.REF.chassaing.2007.1046" rid="pxe.REF.chassaing.2007.1046">Chassaing et al [2007]</a>, <a class="bibr" href="#pxe.REF.iwanaga.2017.644" rid="pxe.REF.iwanaga.2017.644">Iwanaga et al [2017]</a>, <a class="bibr" href="#pxe.REF.legrand.2017.909" rid="pxe.REF.legrand.2017.909">Legrand et al [2017]</a></p></div></dd></dl><dl class="bkr_refwrap"><dt>5. </dt><dd><div id="pxe.TF.1.5"><p class="no_margin">Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. Gene-targeted deletion/duplication testing will detect deletions ranging from a single exon to the whole gene; however, breakpoints of large deletions and/or deletion of adjacent genes (e.g., those described by <a class="bibr" href="#pxe.REF.miksch.2005.235" rid="pxe.REF.miksch.2005.235">Miksch et al [2005]</a> and <a class="bibr" href="#pxe.REF.kringen.2015.233" rid="pxe.REF.kringen.2015.233">Kringen et al [2015]</a>) may not be detected by these methods.</p></div></dd></dl><dl class="bkr_refwrap"><dt>6. </dt><dd><div id="pxe.TF.1.6"><p class="no_margin">Note, MLPA analysis using a widely available commercial kit does not include probes for exons 1, 3, 6, 16, 19-20, 29, and 31.</p></div></dd></dl><dl class="bkr_refwrap"><dt>7. </dt><dd><div id="pxe.TF.1.7"><p class="no_margin">A deletion of exons 23-29 is common (~11% of alleles in affected individuals) in European populations [<a class="bibr" href="#pxe.REF.legrand.2017.909" rid="pxe.REF.legrand.2017.909">Legrand et al 2017</a>], and a deletion of exons 1-4 is common (~10% of alleles in affected individuals) in the Japanese population [<a class="bibr" href="#pxe.REF.iwanaga.2017.644" rid="pxe.REF.iwanaga.2017.644">Iwanaga et al 2017</a>].</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobpxeTselectfeaturesofpseudoxanthoma"><div id="pxe.T.select_features_of_pseudoxanthoma" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p>Select Features of Pseudoxanthoma Elasticum (PXE)</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1113/table/pxe.T.select_features_of_pseudoxanthoma/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__pxe.T.select_features_of_pseudoxanthoma_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_pxe.T.select_features_of_pseudoxanthoma_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Feature</th><th id="hd_h_pxe.T.select_features_of_pseudoxanthoma_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">% of Persons<br />with Feature</th><th id="hd_h_pxe.T.select_features_of_pseudoxanthoma_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Comment</th></tr></thead><tbody><tr><td headers="hd_h_pxe.T.select_features_of_pseudoxanthoma_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Skin lesions</td><td headers="hd_h_pxe.T.select_features_of_pseudoxanthoma_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">100%</td><td headers="hd_h_pxe.T.select_features_of_pseudoxanthoma_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">In advanced stages, skin can become lax & redundant; sometimes reconstructive surgery is necessary.</td></tr><tr><td headers="hd_h_pxe.T.select_features_of_pseudoxanthoma_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Retinal involvement</td><td headers="hd_h_pxe.T.select_features_of_pseudoxanthoma_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">100%</td><td headers="hd_h_pxe.T.select_features_of_pseudoxanthoma_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Subretinal neovascularization w/hemorrhage can cause significant visual impairment.</td></tr><tr><td headers="hd_h_pxe.T.select_features_of_pseudoxanthoma_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Vascular (arterial<br />arrowing)</td><td headers="hd_h_pxe.T.select_features_of_pseudoxanthoma_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">60%</td><td headers="hd_h_pxe.T.select_features_of_pseudoxanthoma_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Can cause claudication, small strokes, intestinal angina, renovascular hypertension, angina &/or myocardial infarction</td></tr><tr><td headers="hd_h_pxe.T.select_features_of_pseudoxanthoma_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">GI bleeding</td><td headers="hd_h_pxe.T.select_features_of_pseudoxanthoma_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">10%</td><td headers="hd_h_pxe.T.select_features_of_pseudoxanthoma_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Most commonly in the upper GI tract</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">Based on <a class="bibr" href="#pxe.REF.uitto.2014.567" rid="pxe.REF.uitto.2014.567">Uitto et al [2014]</a></p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">GI = gastrointestinal</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobpxeTgenesofinterestinthedifferent"><div id="pxe.T.genes_of_interest_in_the_different" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Genes of Interest in the Differential Diagnosis of Pseudoxanthoma Elasticum (PXE)</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1113/table/pxe.T.genes_of_interest_in_the_different/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__pxe.T.genes_of_interest_in_the_different_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_pxe.T.genes_of_interest_in_the_different_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene(s)</th><th id="hd_h_pxe.T.genes_of_interest_in_the_different_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Disorder</th><th id="hd_h_pxe.T.genes_of_interest_in_the_different_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">MOI</th><th id="hd_h_pxe.T.genes_of_interest_in_the_different_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Clinical Features Overlapping w/PXE</th><th id="hd_h_pxe.T.genes_of_interest_in_the_different_1_1_1_5" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Differentiating Features</th></tr></thead><tbody><tr><td headers="hd_h_pxe.T.genes_of_interest_in_the_different_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>ATP6V0A2</i><br /><i>EFEMP2</i><br /><i>ELN</i><br /><i>FBLN5</i><br /><i>LTBP4</i> <sup>1</sup></td><td headers="hd_h_pxe.T.genes_of_interest_in_the_different_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cutis laxa (See <a href="/books/n/gene/cutis-laxa/?report=reader"><i>ATP6V0A2</i>-Related Cutis Laxa</a>, <a href="/books/n/gene/fbln5-cutis-laxa/?report=reader"><i>FBLN5</i>-Related Cutis Laxa</a>, <a href="/books/n/gene/efemp2-cutis-laxa/?report=reader"><i>EFEMP2</i>-Related Cutis Laxa</a>, <a href="/books/n/gene/eln-cutis-laxa/?report=reader"><i>ELN</i>-Related Cutis Laxa</a>, and <a href="/books/n/gene/ltbp4-cutis-laxa/?report=reader"><i>LTBP4</i>-Related Cutis Laxa</a>.)</td><td headers="hd_h_pxe.T.genes_of_interest_in_the_different_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR<br />AD</td><td headers="hd_h_pxe.T.genes_of_interest_in_the_different_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Loose & sagging skin mimicking PXE; no discrete papules or plaques</td><td headers="hd_h_pxe.T.genes_of_interest_in_the_different_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Skin lesions appear over the entire body; in PXE they are limited to the flexor areas.</td></tr><tr><td headers="hd_h_pxe.T.genes_of_interest_in_the_different_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ENPP1</i>
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</td><td headers="hd_h_pxe.T.genes_of_interest_in_the_different_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a href="/books/n/gene/gaci/?report=reader">Generalized arterial calcification of infancy</a> (GACI)</td><td headers="hd_h_pxe.T.genes_of_interest_in_the_different_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_pxe.T.genes_of_interest_in_the_different_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Severe arteriopathy</div></li><li class="half_rhythm"><div>Children w/GACI may also develop the typical cutaneous & ocular phenotype of PXE. <sup>2</sup></div></li></ul>
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</td><td headers="hd_h_pxe.T.genes_of_interest_in_the_different_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">GACI is very severe in children; PXE is very mild & often not apparent in childhood.</td></tr><tr><td headers="hd_h_pxe.T.genes_of_interest_in_the_different_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>FGF23</i>
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<br />
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<i>GALNT3</i>
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<br />
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<i>KL</i>
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</td><td headers="hd_h_pxe.T.genes_of_interest_in_the_different_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/hyper-ftc/?report=reader">Hyperphosphatemic familial tumoral calcinosis</a>
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</td><td headers="hd_h_pxe.T.genes_of_interest_in_the_different_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_pxe.T.genes_of_interest_in_the_different_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Angioid streaks in the retina <sup>3</sup></td><td headers="hd_h_pxe.T.genes_of_interest_in_the_different_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Skin lesions are present in PXE.</td></tr><tr><td headers="hd_h_pxe.T.genes_of_interest_in_the_different_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>GGCX</i>
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</td><td headers="hd_h_pxe.T.genes_of_interest_in_the_different_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">PXE-like disorder w/multiple coagulation factor deficiency (OMIM <a href="https://omim.org/entry/610842" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">610842</a>)</td><td headers="hd_h_pxe.T.genes_of_interest_in_the_different_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_pxe.T.genes_of_interest_in_the_different_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cutis laxa-like skin changes w/histolopathologic changes of PXE & deficiency of vitamin K-dependent clotting factors</td><td headers="hd_h_pxe.T.genes_of_interest_in_the_different_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">No issues w/clotting in PXE</td></tr><tr><td headers="hd_h_pxe.T.genes_of_interest_in_the_different_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>HBB</i>
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</td><td headers="hd_h_pxe.T.genes_of_interest_in_the_different_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/b-thal/?report=reader">Beta-thalassemia</a>
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</td><td headers="hd_h_pxe.T.genes_of_interest_in_the_different_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_pxe.T.genes_of_interest_in_the_different_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">PXE-like phenotype (skin, eye [angioid streaks in the retina <sup>3</sup>], & cardiovascular)</td><td headers="hd_h_pxe.T.genes_of_interest_in_the_different_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Although similar, the angioid streaks are not concurrent w/skin lesions.</td></tr><tr><td headers="hd_h_pxe.T.genes_of_interest_in_the_different_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>HBB</i>
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</td><td headers="hd_h_pxe.T.genes_of_interest_in_the_different_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sickle thalassemia (See <a href="/books/n/gene/sickle/?report=reader">Sickle Cell Disease</a>.)</td><td headers="hd_h_pxe.T.genes_of_interest_in_the_different_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_pxe.T.genes_of_interest_in_the_different_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Angioid streaks in the retina <sup>3</sup></td><td headers="hd_h_pxe.T.genes_of_interest_in_the_different_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Although similar, the angioid streaks are not concurrent w/skin lesions.</td></tr><tr><td headers="hd_h_pxe.T.genes_of_interest_in_the_different_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>LEMD3</i>
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</td><td headers="hd_h_pxe.T.genes_of_interest_in_the_different_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Buschke-Ollendorf syndrome (BOS) (OMIM <a href="https://omim.org/entry/166700" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">166700</a>)</td><td headers="hd_h_pxe.T.genes_of_interest_in_the_different_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_pxe.T.genes_of_interest_in_the_different_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Osteopoikilosis assoc w/cutaneous papules w/accumulation of elastin in dermis</td><td headers="hd_h_pxe.T.genes_of_interest_in_the_different_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>On skin biopsy, PXE does not have the same extent of abnormal collagen fibers near the calcified elastic fibers.</div></li><li class="half_rhythm"><div>The skin lesions in BOS do not calcify histopathologically.</div></li><li class="half_rhythm"><div>No osteopoikilosis in PXE</div></li></ul>
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</td></tr><tr><td headers="hd_h_pxe.T.genes_of_interest_in_the_different_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>PDB4</i>
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<br />
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<i>SQSTM1</i>
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<br />
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<i>TNFRSF11A</i>
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<br />
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<i>TNFRSF11B</i>
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<br />
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<i>ZNF687</i>
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</td><td headers="hd_h_pxe.T.genes_of_interest_in_the_different_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Paget disease of bone (OMIM <a href="https://omim.org/phenotypicSeries/PS167250" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PS167250</a>)</td><td headers="hd_h_pxe.T.genes_of_interest_in_the_different_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD<br />AR</td><td headers="hd_h_pxe.T.genes_of_interest_in_the_different_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Angioid streaks in the retina <sup>3</sup></td><td headers="hd_h_pxe.T.genes_of_interest_in_the_different_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">No skin lesions in Paget disease of bone</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">AD = autosomal dominant; AR = autosomal recessive; MOI = mode of inheritance</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="pxe.TF.3.1"><p class="no_margin">Cutis laxa may also be associated with pathogenic variants in <i>ALDH18A1</i>, <i>ATP6V1A</i>, <i>ATP6V1E1</i>, or <i>PYCR1</i> (see OMIM <a href="https://omim.org/phenotypicSeries/PS123700?sort=geneSymbols" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Cutis Laxa Phenotypic Series</a>).</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="pxe.TF.3.2"><p class="no_margin">
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<a class="bibr" href="#pxe.REF.nitschke.2012.25" rid="pxe.REF.nitschke.2012.25">Nitschke et al [2012]</a>
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</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="pxe.TF.3.3"><p class="no_margin">PXE is the most common cause of angioid streaks of the retina.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobpxeTrecommendedevaluationsfollowing"><div id="pxe.T.recommended_evaluations_following" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p>Recommended Evaluations Following Initial Diagnosis in Individuals with Pseudoxanthoma Elasticum (PXE)</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1113/table/pxe.T.recommended_evaluations_following/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__pxe.T.recommended_evaluations_following_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_pxe.T.recommended_evaluations_following_1_1_1_1" colspan="2" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_pxe.T.recommended_evaluations_following_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_pxe.T.recommended_evaluations_following_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment</th></tr></thead><tbody><tr><td headers="hd_h_pxe.T.recommended_evaluations_following_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<b>Skin</b>
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</td><td headers="hd_h_pxe.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complete skin exam w/biopsy (if not done previously) by dermatologist</td><td headers="hd_h_pxe.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To establish a baseline</td></tr><tr><td headers="hd_h_pxe.T.recommended_evaluations_following_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<b>Eye</b>
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</td><td headers="hd_h_pxe.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complete exam by retinal specialist incl best corrected visual acuity, Amsler grid, OCT, <sup>1</sup> & retinal exam for neovascularization & macular atrophy</td><td headers="hd_h_pxe.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Early recognition of choroidal neovascularization assoc w/angioid streaks allows prompt treatment w/anti-angiogenesis drugs & appropriate surveillance.</td></tr><tr><td headers="hd_h_pxe.T.recommended_evaluations_following_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<b>Reduced vision</b>
|
|
</td><td headers="hd_h_pxe.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consultation w/agencies for the visually impaired <sup>1</sup></td><td headers="hd_h_pxe.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Use of low vision aids <sup>2</sup></td></tr><tr><td headers="hd_h_pxe.T.recommended_evaluations_following_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Gastrointestinal (bleeding, angina)</b>
|
|
</td><td headers="hd_h_pxe.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Obtain past medical history & medical records for findings consistent w/these potential complications</td><td headers="hd_h_pxe.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Referral to gastroenterologist</td></tr><tr><td headers="hd_h_pxe.T.recommended_evaluations_following_1_1_1_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Vascular</b>
|
|
</td><td headers="hd_h_pxe.T.recommended_evaluations_following_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Claudication of leg</b>
|
|
<br />
|
|
<b>&/or arm muscles</b>
|
|
</td><td headers="hd_h_pxe.T.recommended_evaluations_following_1_1_1_2" rowspan="3" colspan="1" style="text-align:left;vertical-align:middle;">Obtain past medical history & medical records for findings consistent w/these potential vascular complications</td><td headers="hd_h_pxe.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Referral to vascular clinic</td></tr><tr><td headers="hd_h_pxe.T.recommended_evaluations_following_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Stroke</b>
|
|
</td><td headers="hd_h_pxe.T.recommended_evaluations_following_1_1_1_3" colspan="1" rowspan="1" style="text-align:left;vertical-align:middle;">Referral to neurologist/stroke clinic</td></tr><tr><td headers="hd_h_pxe.T.recommended_evaluations_following_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Renovascular</b>
|
|
<br />
|
|
<b>hypertension</b>
|
|
</td><td headers="hd_h_pxe.T.recommended_evaluations_following_1_1_1_3" colspan="1" rowspan="1" style="text-align:left;vertical-align:middle;">Referral to nephrologist</td></tr><tr><td headers="hd_h_pxe.T.recommended_evaluations_following_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Cardiovascular assessment</b>
|
|
</td><td headers="hd_h_pxe.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Referral to cardiologist for baseline exam</td><td headers="hd_h_pxe.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cardiovascular issues (if present) may be exacerbated by PXE.</td></tr><tr><td headers="hd_h_pxe.T.recommended_evaluations_following_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Other</b>
|
|
</td><td headers="hd_h_pxe.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consultation w/clinical geneticist &/or genetic counselor</td><td headers="hd_h_pxe.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">OCT = optical coherence tomography</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="pxe.TF.4.1"><p class="no_margin">In the US, publicly funded agencies at the state level provide services for the blind or those with progressive eye disorders; services include vocational training, mobility training, and skills for independent living.</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="pxe.TF.4.2"><p class="no_margin">Low vision aids such as magnifiers and closed-circuit television may provide useful reading vision for individuals with reduced central acuity.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobpxeTtreatmentofmanifestationsinind"><div id="pxe.T.treatment_of_manifestations_in_ind" class="table"><h3><span class="label">Table 5. </span></h3><div class="caption"><p>Treatment of Manifestations in Individuals with Pseudoxanthoma Elasticum (PXE)</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1113/table/pxe.T.treatment_of_manifestations_in_ind/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__pxe.T.treatment_of_manifestations_in_ind_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_pxe.T.treatment_of_manifestations_in_ind_1_1_1_1" colspan="2" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_pxe.T.treatment_of_manifestations_in_ind_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment</th><th id="hd_h_pxe.T.treatment_of_manifestations_in_ind_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Considerations/Other</th></tr></thead><tbody><tr><td headers="hd_h_pxe.T.treatment_of_manifestations_in_ind_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Skin</b>
|
|
</td><td headers="hd_h_pxe.T.treatment_of_manifestations_in_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reconstructive surgery <sup>1</sup></td><td headers="hd_h_pxe.T.treatment_of_manifestations_in_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reconstructive surgery may be indicated to improve skin changes of the face, neck, axilla, & groin that are causing infection & inflammation.</td></tr><tr><td headers="hd_h_pxe.T.treatment_of_manifestations_in_ind_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Eye</b>
|
|
</td><td headers="hd_h_pxe.T.treatment_of_manifestations_in_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Current treatment for macular neovascularization, incl intravitreal injection of anti-angiogenic drugs <sup>2</sup></td><td headers="hd_h_pxe.T.treatment_of_manifestations_in_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consult a retinal specialist immediately for any distortion in vision or ↓ in visual acuity.</td></tr><tr><td headers="hd_h_pxe.T.treatment_of_manifestations_in_ind_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Gastrointestinal</b>
|
|
</td><td headers="hd_h_pxe.T.treatment_of_manifestations_in_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Surgical intervention may be indicated for Gl bleeding. <sup>3</sup></td><td headers="hd_h_pxe.T.treatment_of_manifestations_in_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Avoid use of aspirin & NSAIDs to ↓ risk of GI bleeding.</td></tr><tr><td headers="hd_h_pxe.T.treatment_of_manifestations_in_ind_1_1_1_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Vascular</b>
|
|
</td><td headers="hd_h_pxe.T.treatment_of_manifestations_in_ind_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Claudication of leg</b>
|
|
<br />
|
|
<b>&/or arm muscles</b>
|
|
</td><td headers="hd_h_pxe.T.treatment_of_manifestations_in_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Per treating vascular clinic/surgeon <sup>4</sup></td><td headers="hd_h_pxe.T.treatment_of_manifestations_in_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_pxe.T.treatment_of_manifestations_in_ind_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Stroke</b>
|
|
</td><td headers="hd_h_pxe.T.treatment_of_manifestations_in_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Per treating stroke clinic/neurologist</td><td headers="hd_h_pxe.T.treatment_of_manifestations_in_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_pxe.T.treatment_of_manifestations_in_ind_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Renovascular</b>
|
|
<br />
|
|
<b>hypertension</b>
|
|
</td><td headers="hd_h_pxe.T.treatment_of_manifestations_in_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Per treating nephrologist <sup>4</sup></td><td headers="hd_h_pxe.T.treatment_of_manifestations_in_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_pxe.T.treatment_of_manifestations_in_ind_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Cardiovascular complications</b>
|
|
<br />
|
|
<b>(angina, MI)</b>
|
|
</td><td headers="hd_h_pxe.T.treatment_of_manifestations_in_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Mgmt of angina &/or prior MI per treating cardiologist/cardiovascular surgeon <sup>5</sup></td><td headers="hd_h_pxe.T.treatment_of_manifestations_in_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">GI = gastrointestinal; MI = myocardial infarction; NSAIDs = nonsteroidal anti-inflammatory drugs</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="pxe.TF.5.1"><p class="no_margin">As directed by a dermatologist or plastic surgeon</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="pxe.TF.5.2"><p class="no_margin"><a class="bibr" href="#pxe.REF.mimoun.2017.1651" rid="pxe.REF.mimoun.2017.1651">Mimoun et al [2017]</a>, <a class="bibr" href="#pxe.REF.battaglia_parodi.2019.273" rid="pxe.REF.battaglia_parodi.2019.273">Battaglia Parodi et al [2019]</a></p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="pxe.TF.5.3"><p class="no_margin">Bleeding may be difficult to control without surgery [<a class="bibr" href="#pxe.REF.dalle.2002.213" rid="pxe.REF.dalle.2002.213">Dalle & Geboes 2002</a>].</p></div></dd></dl><dl class="bkr_refwrap"><dt>4. </dt><dd><div id="pxe.TF.5.4"><p class="no_margin">See <a class="bibr" href="#pxe.REF.anderson.2013.1425" rid="pxe.REF.anderson.2013.1425">Anderson et al [2013]</a> for clinical practice guidelines on the management of individuals with peripheral artery disease.</p></div></dd></dl><dl class="bkr_refwrap"><dt>5. </dt><dd><div id="pxe.TF.5.5"><p class="no_margin">See <a class="bibr" href="#pxe.REF.fihn.2012.e44" rid="pxe.REF.fihn.2012.e44">Fihn et al [2012]</a> and <a class="bibr" href="#pxe.REF.fihn.2014.1929" rid="pxe.REF.fihn.2014.1929">Fihn et al [2014]</a> for clinical practice guidelines on the management of individuals with stable ischemic heart disease.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobpxeTrecommendedsurveillanceforindiv"><div id="pxe.T.recommended_surveillance_for_indiv" class="table"><h3><span class="label">Table 6. </span></h3><div class="caption"><p>Recommended Surveillance for Individuals with Pseudoxanthoma Elasticum (PXE)</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1113/table/pxe.T.recommended_surveillance_for_indiv/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__pxe.T.recommended_surveillance_for_indiv_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_pxe.T.recommended_surveillance_for_indiv_1_1_1_1" colspan="2" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_pxe.T.recommended_surveillance_for_indiv_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_pxe.T.recommended_surveillance_for_indiv_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Frequency</th></tr></thead><tbody><tr><td headers="hd_h_pxe.T.recommended_surveillance_for_indiv_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Skin</b>
|
|
</td><td headers="hd_h_pxe.T.recommended_surveillance_for_indiv_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consultation w/cosmetic dermatologist or reconstructive surgeon if redundant skin presents risk of infection</td><td headers="hd_h_pxe.T.recommended_surveillance_for_indiv_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Per patient</td></tr><tr><td headers="hd_h_pxe.T.recommended_surveillance_for_indiv_1_1_1_1" rowspan="2" colspan="2" scope="row" style="text-align:left;vertical-align:middle;">
|
|
<b>Eye</b>
|
|
</td><td headers="hd_h_pxe.T.recommended_surveillance_for_indiv_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Retinal exam by retinal specialist</td><td headers="hd_h_pxe.T.recommended_surveillance_for_indiv_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Annually or more frequently per treating ophthalmologist when retinal neovascularization is active &/or treatment is ongoing</td></tr><tr><td headers="hd_h_pxe.T.recommended_surveillance_for_indiv_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Patient use of Amsler grid to monitor for central visual disturbances</td><td headers="hd_h_pxe.T.recommended_surveillance_for_indiv_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Daily</td></tr><tr><td headers="hd_h_pxe.T.recommended_surveillance_for_indiv_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Gastrointestinal</b>
|
|
</td><td headers="hd_h_pxe.T.recommended_surveillance_for_indiv_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Per treating gastroenterologist</td><td headers="hd_h_pxe.T.recommended_surveillance_for_indiv_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Per treating gastroenterologist</td></tr><tr><td headers="hd_h_pxe.T.recommended_surveillance_for_indiv_1_1_1_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Vascular</b>
|
|
</td><td headers="hd_h_pxe.T.recommended_surveillance_for_indiv_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Claudication of leg</b>
|
|
<br />
|
|
<b>&/or arm muscles</b>
|
|
</td><td headers="hd_h_pxe.T.recommended_surveillance_for_indiv_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Per treating vascular clinic/surgeon</td><td headers="hd_h_pxe.T.recommended_surveillance_for_indiv_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Per treating vascular clinic/surgeon</td></tr><tr><td headers="hd_h_pxe.T.recommended_surveillance_for_indiv_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Stroke</b>
|
|
</td><td headers="hd_h_pxe.T.recommended_surveillance_for_indiv_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Per treating stroke clinic/neurologist</td><td headers="hd_h_pxe.T.recommended_surveillance_for_indiv_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Per treating stroke clinic/neurologist</td></tr><tr><td headers="hd_h_pxe.T.recommended_surveillance_for_indiv_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Renovascular</b>
|
|
<br />
|
|
<b>hypertension</b>
|
|
</td><td headers="hd_h_pxe.T.recommended_surveillance_for_indiv_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Per treating nephrologist</td><td headers="hd_h_pxe.T.recommended_surveillance_for_indiv_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Per treating nephrologist</td></tr><tr><td headers="hd_h_pxe.T.recommended_surveillance_for_indiv_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Cardiovascular complications</b>
|
|
<br />
|
|
<b>angina, MI)</b>
|
|
</td><td headers="hd_h_pxe.T.recommended_surveillance_for_indiv_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Per treating cardiologist</td><td headers="hd_h_pxe.T.recommended_surveillance_for_indiv_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Per treating cardiologist</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">MI = myocardial infarction</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobpxemolgenTA"><div id="pxe.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>Pseudoxanthoma Elasticum: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1113/table/pxe.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__pxe.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_pxe.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_pxe.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_pxe.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_pxe.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">Locus-Specific Databases</th><th id="hd_b_pxe.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_pxe.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_pxe.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="/gene/368" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
|
<i>ABCC6</i>
|
|
</a>
|
|
</td><td headers="hd_b_pxe.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/genome/gdv/?context=gene&acc=368" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">16p13<wbr style="display:inline-block"></wbr>​.11</a>
|
|
</td><td headers="hd_b_pxe.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.uniprot.org/uniprot/O95255" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ATP-binding cassette sub-family C member 6</a>
|
|
</td><td headers="hd_b_pxe.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.lovd.nl/ABCC6" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ABCC6 @ LOVD</a>
|
|
</td><td headers="hd_b_pxe.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=ABCC6" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ABCC6</a>
|
|
</td><td headers="hd_b_pxe.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=ABCC6[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ABCC6</a>
|
|
</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div id="pxe.TFA.1"><p class="no_margin">Data are compiled from the following standard references: gene from
|
|
<a href="http://www.genenames.org/index.html" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">HGNC</a>;
|
|
chromosome locus from
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<a href="http://www.omim.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">OMIM</a>;
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protein from <a href="http://www.uniprot.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">UniProt</a>.
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For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click
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<a href="/books/n/gene/app1/?report=reader">here</a>.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobpxemolgenTB"><div id="pxe.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for Pseudoxanthoma Elasticum (<a href="/omim/177850,264800,603234" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">View All in OMIM</a>) </p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1113/table/pxe.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__pxe.molgen.TB_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/177850" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">177850</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">PSEUDOXANTHOMA ELASTICUM, FORME FRUSTE</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/264800" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">264800</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">PSEUDOXANTHOMA ELASTICUM; PXE</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/603234" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">603234</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">ATP-BINDING CASSETTE, SUBFAMILY C, MEMBER 6; ABCC6</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobpxeTnotableabcc6pathogenicvariants"><div id="pxe.T.notable_abcc6_pathogenic_variants" class="table"><h3><span class="label">Table 7. </span></h3><div class="caption"><p>Notable <i>ABCC6</i> Pathogenic Variants</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1113/table/pxe.T.notable_abcc6_pathogenic_variants/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__pxe.T.notable_abcc6_pathogenic_variants_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_pxe.T.notable_abcc6_pathogenic_variants_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference Sequences</th><th id="hd_h_pxe.T.notable_abcc6_pathogenic_variants_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DNA Nucleotide<br />Change</th><th id="hd_h_pxe.T.notable_abcc6_pathogenic_variants_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Predicted<br />Protein Change</th><th id="hd_h_pxe.T.notable_abcc6_pathogenic_variants_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment [Reference]</th></tr></thead><tbody><tr><td headers="hd_h_pxe.T.notable_abcc6_pathogenic_variants_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_001171.5" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_001171<wbr style="display:inline-block"></wbr>​.5</a>
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<br />
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<a href="https://www.ncbi.nlm.nih.gov/protein/NP_001162.4" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_001162<wbr style="display:inline-block"></wbr>​.4</a>
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</td><td headers="hd_h_pxe.T.notable_abcc6_pathogenic_variants_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.3421C>T</td><td headers="hd_h_pxe.T.notable_abcc6_pathogenic_variants_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Arg1141Ter</td><td headers="hd_h_pxe.T.notable_abcc6_pathogenic_variants_1_1_1_4" rowspan="2" colspan="1" style="text-align:left;vertical-align:top;">Most common (in descending order) disease-associated variants in European populations [<a class="bibr" href="#pxe.REF.legrand.2017.909" rid="pxe.REF.legrand.2017.909">Legrand et al 2017</a>]</td></tr><tr><td headers="hd_h_pxe.T.notable_abcc6_pathogenic_variants_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_001171.5" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_001171<wbr style="display:inline-block"></wbr>​.5</a>
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</td><td headers="hd_h_pxe.T.notable_abcc6_pathogenic_variants_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Exon 23-29 deletion</td><td headers="hd_h_pxe.T.notable_abcc6_pathogenic_variants_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">--</td></tr><tr><td headers="hd_h_pxe.T.notable_abcc6_pathogenic_variants_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_001171.5" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_001171<wbr style="display:inline-block"></wbr>​.5</a>
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<br />
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<a href="https://www.ncbi.nlm.nih.gov/protein/NP_001162.4" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_001162<wbr style="display:inline-block"></wbr>​.4</a>
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</td><td headers="hd_h_pxe.T.notable_abcc6_pathogenic_variants_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.2542delG</td><td headers="hd_h_pxe.T.notable_abcc6_pathogenic_variants_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Val848CysfsTer83</td><td headers="hd_h_pxe.T.notable_abcc6_pathogenic_variants_1_1_1_4" rowspan="3" colspan="1" style="text-align:left;vertical-align:middle;">Most common (in descending order) pathogenic variants in the Japanese population [<a class="bibr" href="#pxe.REF.iwanaga.2017.644" rid="pxe.REF.iwanaga.2017.644">Iwanaga et al 2017</a>]</td></tr><tr><td headers="hd_h_pxe.T.notable_abcc6_pathogenic_variants_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.1132C>T</td><td headers="hd_h_pxe.T.notable_abcc6_pathogenic_variants_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Glu378Ter</td></tr><tr><td headers="hd_h_pxe.T.notable_abcc6_pathogenic_variants_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_001171.5" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_001171<wbr style="display:inline-block"></wbr>​.5</a>
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</td><td headers="hd_h_pxe.T.notable_abcc6_pathogenic_variants_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Exon 1-4 deletion</td><td headers="hd_h_pxe.T.notable_abcc6_pathogenic_variants_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">--</td></tr><tr><td headers="hd_h_pxe.T.notable_abcc6_pathogenic_variants_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_001171.5" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_001171<wbr style="display:inline-block"></wbr>​.5</a>
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<br />
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<a href="https://www.ncbi.nlm.nih.gov/protein/NP_001162.4" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_001162<wbr style="display:inline-block"></wbr>​.4</a>
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</td><td headers="hd_h_pxe.T.notable_abcc6_pathogenic_variants_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.4015C>T</td><td headers="hd_h_pxe.T.notable_abcc6_pathogenic_variants_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Arg1339Cys</td><td headers="hd_h_pxe.T.notable_abcc6_pathogenic_variants_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Founder variant that accounts for ~50% of disease alleles in the Afrikaner population [<a class="bibr" href="#pxe.REF.le_saux.2002.331" rid="pxe.REF.le_saux.2002.331">Le Saux et al 2002</a>]</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">Variants listed in the table have been provided by the authors. <i>GeneReviews</i> staff have not independently verified the classification of variants.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin"><i>GeneReviews</i> follows the standard naming conventions of the Human Genome Variation Society (<a href="https://varnomen.hgvs.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">varnomen<wbr style="display:inline-block"></wbr>​.hgvs.org</a>). See <a href="/books/n/gene/app3/?report=reader">Quick Reference</a> for an explanation of nomenclature.</p></div></dd></dl></dl></div></div></div></article></div><div id="jr-scripts"><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/libs.min.js"> </script><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.min.js"> </script><script type="text/javascript">if (typeof (jQuery) != 'undefined') { (function ($) { $(function () { var min = Math.ceil(1); var max = Math.floor(100000); var randomNum = Math.floor(Math.random() * (max - min)) + min; var surveyUrl = "/projects/Gene/portal/surveys/seqdbui-survey.js?rando=" + randomNum.toString(); $.getScript(surveyUrl, function () { try { ncbi.seqDbUISurvey.init(); } catch (err) { console.info(err); } }).fail(function (jqxhr, settings, exception) { console.info('Cannot load survey script', jqxhr); });; }); })(jQuery); };</script></div></div>
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