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Pseudoxanthoma elasticum(PXE)

MedGen UID:
18733
Concept ID:
C0033847
Disease or Syndrome
Synonyms: Autosomal recessive inherited pseudoxanthoma elasticum; Gronblad Strandberg syndrome; PXE
SNOMED CT: Pseudoxanthoma elasticum (252246005); PXE - Pseudoxanthoma elasticum (252246005)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Genes (locations): ABCC6 (16p13.11); XYLT1 (16p12.3); XYLT2 (17q21.33)
 
Monarch Initiative: MONDO:0009925
OMIM®: 264800
Orphanet: ORPHA758

Disease characteristics

Excerpted from the GeneReview: Pseudoxanthoma Elasticum
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. [from GeneReviews]
Authors:
Sharon F Terry  |  Jouni Uitto   view full author information

Additional descriptions

From OMIM
Pseudoxanthoma elasticum is an inherited multisystem disorder that is associated with accumulation of mineralized and fragmented elastic fibers in the skin, vascular walls, and Bruch membrane in the eye. Clinically, patients exhibit characteristic lesions of the posterior segment of the eye, including peau d'orange, angioid streaks, and choroidal neovascularizations (CNVs); of the skin, including soft, ivory colored papules in a reticular pattern that predominantly affect the neck and large flexor surfaces; and of the cardiovascular system, with peripheral and coronary arterial occlusive disease as well as gastrointestinal bleedings (summary by Finger et al., 2009). Generalized arterial calcification of infancy-2 (GACI2; 614473) is an allelic disorder, also caused by homozygous or compound heterozygous mutation in the ABCC6 gene; it has been suggested that GACI and PXE represent 2 ends of a clinical spectrum of ectopic calcification and other organ pathologies rather than 2 distinct disorders (Nitschke et al., 2012).  http://www.omim.org/entry/264800
From MedlinePlus Genetics
Pseudoxanthoma elasticum (PXE) is a progressive disorder that is characterized by the accumulation of deposits of calcium and other minerals (mineralization) in elastic fibers. Elastic fibers are a component of connective tissue, which provides strength and flexibility to structures throughout the body.

In PXE, mineralization can affect elastic fibers in the skin, eyes, and blood vessels, and less frequently in other areas such as the digestive tract. People with PXE may have yellowish bumps called papules on their necks, underarms, and other areas of skin that touch when a joint bends (flexor areas). They may also have abnormalities in the eyes, such as a change in the pigmented cells of the retina (the light-sensitive layer of cells at the back of the eye) known as peau d'orange. Another eye abnormality known as angioid streaks occurs when tiny breaks form in the layer of tissue under the retina called Bruch's membrane. Bleeding and scarring of the retina may also occur, which can cause vision loss.

Mineralization of the blood vessels that carry blood from the heart to the rest of the body (arteries) may cause other signs and symptoms of PXE. For example, people with this condition can develop narrowing of the arteries (arteriosclerosis) or a condition called claudication that is characterized by cramping and pain during exercise due to decreased blood flow to the arms and legs. Rarely, bleeding from blood vessels in the digestive tract may also occur.  https://medlineplus.gov/genetics/condition/pseudoxanthoma-elasticum

Clinical features

From HPO
Renovascular hypertension
MedGen UID:
43786
Concept ID:
C0020545
Disease or Syndrome
The presence of hypertension related to stenosis of the renal artery.
Angina pectoris
MedGen UID:
1929
Concept ID:
C0002962
Sign or Symptom
Paroxysmal chest pain that occurs with exertion or stress and is related to myocardial ischemia.
Restrictive cardiomyopathy
MedGen UID:
40111
Concept ID:
C0007196
Disease or Syndrome
Restrictive left ventricular physiology is characterized by a pattern of ventricular filling in which increased stiffness of the myocardium causes ventricular pressure to rise precipitously with only small increases in volume, defined as restrictive ventricular physiology in the presence of normal or reduced diastolic volumes (of one or both ventricles), normal or reduced systolic volumes, and normal ventricular wall thickness.
Coronary artery atherosclerosis
MedGen UID:
3623
Concept ID:
C0010054
Disease or Syndrome
Reduction of the diameter of the coronary arteries as the result of an accumulation of atheromatous plaques within the walls of the coronary arteries, which increases the risk of myocardial ischemia.
Congestive heart failure
MedGen UID:
9169
Concept ID:
C0018802
Disease or Syndrome
The presence of an abnormality of cardiac function that is responsible for the failure of the heart to pump blood at a rate that is commensurate with the needs of the tissues or a state in which abnormally elevated filling pressures are required for the heart to do so. Heart failure is frequently related to a defect in myocardial contraction.
Hypertensive disorder
MedGen UID:
6969
Concept ID:
C0020538
Disease or Syndrome
The presence of chronic increased pressure in the systemic arterial system.
Intermittent claudication
MedGen UID:
7115
Concept ID:
C0021775
Disease or Syndrome
Intermittent claudication is a symptom of peripheral arterial occlusive disease. After having walked over a distance which is individually characteristic, the patients experience pain or cramps in the calves, feet or thighs which typically subsides on standing still.
Mitral valve prolapse
MedGen UID:
7671
Concept ID:
C0026267
Disease or Syndrome
One or both of the leaflets (cusps) of the mitral valve bulges back into the left atrium upon contraction of the left ventricle.
Mitral stenosis
MedGen UID:
44466
Concept ID:
C0026269
Disease or Syndrome
An abnormal narrowing of the orifice of the mitral valve.
Stroke
MedGen UID:
52522
Concept ID:
C0038454
Disease or Syndrome
Sudden impairment of blood flow to a part of the brain due to occlusion or rupture of an artery to the brain.
Weak pulse
MedGen UID:
68554
Concept ID:
C0232132
Finding
A diminution in the amplitude (strength) of the pulse such that the examiner has difficulty feeling the pulse.
Accelerated atherosclerosis
MedGen UID:
376623
Concept ID:
C1849618
Finding
Atherosclerosis which occurs in a person with certain risk factors (e.g., SLE, diabetes, smoking, hypertension, hypercholesterolaemia, family history of early heart disease) at an earlier age than would occur in another person without those risk factors.
Gastrointestinal hemorrhage
MedGen UID:
8971
Concept ID:
C0017181
Pathologic Function
Hemorrhage affecting the gastrointestinal tract.
Decreased DLCO
MedGen UID:
892993
Concept ID:
C4073175
Finding
Reduced ability of the lungs to transfer gas from inspired air to the bloodstream as measured by the diffusing capacity of the lungs for carbon monoxide (DLCO) test.
White oral mucosal macule
MedGen UID:
1716730
Concept ID:
C5398009
Finding
A small circumscribed whitish change in the color of the oral mucosa that is neither elevated nor depressed.
Cutis laxa
MedGen UID:
8206
Concept ID:
C0010495
Disease or Syndrome
Wrinkled, redundant, inelastic and sagging skin.
Civatte bodies
MedGen UID:
90706
Concept ID:
C0333440
Anatomical Abnormality
Eosinophilic hyaline ovoid bodies which are often found in the subepidermal papillary regions or sometimes in the epidermis. Civatte bodies (CBs) are seen as rounded, homogenous, eosinophilic masses on routine H and E staining lying in the deeper parts of epidermis/epithelium and more frequently in dermis/connective tissue. They are known as CBs (in epithelium/epidermis), colloid bodies, or hyaline bodies (in connective tissue). They are 10-25 micrometers in diameter and situated mostly within or above the inflammatory cell infiltrate. In lichen planus, the number of necrotic keratinocytes may be so large that they are seen lying in clusters in the uppermost dermis. These bodies show a positive periodic acid Schiff reaction and are diastase resistant
Yellow papule
MedGen UID:
1373750
Concept ID:
C2033396
Finding
A papule with yellow color.
Angioid streaks of the fundus
MedGen UID:
1541
Concept ID:
C0002982
Disease or Syndrome
Irregular lines in the deep retina that are typically configured in a radiating fashion and emanate from the optic disc. Angioid streaks are crack-like dehiscences in abnormally thickened and calcified Bruch's membrane, resulting in atrophy of the overlying retinal pigment epithelium. They may be associated with a number of endocrine, metabolic, and connective tissue abnormalities but are frequently idiopathic.
Macular degeneration
MedGen UID:
7434
Concept ID:
C0024437
Disease or Syndrome
A nonspecific term denoting degeneration of the retinal pigment epithelium and/or retinal photoreceptor cells of the macula lutea.
Optic disc drusen
MedGen UID:
14495
Concept ID:
C0029128
Disease or Syndrome
Optic disc drusen are acellular, calcified deposits within the optic nerve head. Optic disc drusen are congenital and developmental anomalies of the optic nerve head, representing hyaline-containing bodies that, over time, appear as elevated, lumpy irregularities on the anterior portion of the optic nerve.
Retinal hemorrhage
MedGen UID:
11210
Concept ID:
C0035317
Pathologic Function
Hemorrhage occurring within the retina.
Reduced visual acuity
MedGen UID:
65889
Concept ID:
C0234632
Finding
Diminished clarity of vision.
Choroidal neovascularization
MedGen UID:
154726
Concept ID:
C0600518
Pathologic Function
Choroidal neovascularization (CNV) is the creation of new blood vessels in the choroid layer of the eye.
Visual impairment
MedGen UID:
777085
Concept ID:
C3665347
Finding
Visual impairment (or vision impairment) is vision loss (of a person) to such a degree as to qualify as an additional support need through a significant limitation of visual capability resulting from either disease, trauma, or congenital or degenerative conditions that cannot be corrected by conventional means, such as refractive correction, medication, or surgery.
Retinal peau d'orange
MedGen UID:
1713761
Concept ID:
C5398025
Finding
A pebbly orange appearance of the fundus that is said to resemble the skin of an orange.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Pseudoxanthoma elasticum in Orphanet.

Professional guidelines

PubMed

Bartstra JW, Risseeuw S, de Jong PA, van Os B, Kalsbeek L, Mol C, Baas AF, Verschuere S, Vanakker O, Florijn RJ, Hendrikse J, Mali W, Imhof S, Ossewaarde-van Norel J, van Leeuwen R, Spiering W
Atherosclerosis 2021 May;324:18-26. Epub 2021 Mar 13 doi: 10.1016/j.atherosclerosis.2021.03.012. PMID: 33812167
Camacho M, Rengel C, López-Herrero E, Carrillo JL, Eslava AJ, Valdivielso P
J Obstet Gynaecol 2016 Nov;36(8):1061-1066. Epub 2016 Sep 13 doi: 10.1080/01443615.2016.1196478. PMID: 27623860
Georgalas I, Tservakis I, Papaconstaninou D, Kardara M, Koutsandrea C, Ladas I
Clin Exp Optom 2011 Mar;94(2):169-80. Epub 2010 Dec 29 doi: 10.1111/j.1444-0938.2010.00559.x. PMID: 21198842

Suggested Reading

PubMed

Uitto J, Bercovitch L, Terry SF, Terry PF
Am J Med Genet A 2011 Jul;155A(7):1517-26. Epub 2011 Jun 10 doi: 10.1002/ajmg.a.34067. PMID: 21671388Free PMC Article

Recent clinical studies

Etiology

Saeidian AH, Youssefian L, Huang J, Touati A, Vahidnezhad H, Kowal L, Caffet M, Wurst T, Singh J, Snook AE, Ryu E, Fortina P, Terry SF, Schoenecker JG, Uitto J, Li Q
Genet Med 2022 Jan;24(1):75-86. Epub 2021 Nov 30 doi: 10.1016/j.gim.2021.08.011. PMID: 34906475Free PMC Article
Wightman AJ, Guymer RH
Clin Exp Optom 2019 Sep;102(5):455-462. Epub 2018 Oct 8 doi: 10.1111/cxo.12842. PMID: 30298528
Germain DP
Orphanet J Rare Dis 2017 May 10;12(1):85. doi: 10.1186/s13023-017-0639-8. PMID: 28486967Free PMC Article
Li Q, Arányi T, Váradi A, Terry SF, Uitto J
J Invest Dermatol 2016 Mar;136(3):550-556. doi: 10.1016/j.jid.2015.10.065. PMID: 26902123Free PMC Article
Donaldson EJ
Aust J Ophthalmol 1983 Feb;11(1):55-8. PMID: 6870682

Diagnosis

Brokamp G, Mori M, Faith EF
JAMA Dermatol 2022 Jan 1;158(1):100. doi: 10.1001/jamadermatol.2021.4059. PMID: 34787669
Lucas C, Aranha J, da Rocha I, Sousa D
F1000Res 2020;9:9. Epub 2020 Jan 9 doi: 10.12688/f1000research.21431.1. PMID: 32742638Free PMC Article
Roach ES, Islam MP
Handb Clin Neurol 2015;132:215-21. doi: 10.1016/B978-0-444-62702-5.00015-9. PMID: 26564082
Laube S, Moss C
Arch Dis Child 2005 Jul;90(7):754-6. doi: 10.1136/adc.2004.062075. PMID: 15970621Free PMC Article
Ohtani T, Furukawa F
J Dermatol 2002 Oct;29(10):615-20. doi: 10.1111/j.1346-8138.2002.tb00190.x. PMID: 12432991

Therapy

Bhoiwala DL, Dunaief JL
Surv Ophthalmol 2016 Jan-Feb;61(1):33-50. Epub 2015 Aug 29 doi: 10.1016/j.survophthal.2015.08.005. PMID: 26325202Free PMC Article
Roach ES, Islam MP
Handb Clin Neurol 2015;132:215-21. doi: 10.1016/B978-0-444-62702-5.00015-9. PMID: 26564082
Combemale P, Consort T, Denis-Thelis L, Estival JL, Dupin M, Kanitakis J
Br J Dermatol 2005 Jan;152(1):166-9. doi: 10.1111/j.1365-2133.2005.06340.x. PMID: 15656820
Neldner KH
Int J Dermatol 1988 Mar;27(2):98-100. doi: 10.1111/j.1365-4362.1988.tb01280.x. PMID: 3360560
Neldner KH
Clin Dermatol 1988 Jan-Mar;6(1):1-159. doi: 10.1016/0738-081x(88)90003-x. PMID: 3359381

Prognosis

Saeidian AH, Youssefian L, Huang J, Touati A, Vahidnezhad H, Kowal L, Caffet M, Wurst T, Singh J, Snook AE, Ryu E, Fortina P, Terry SF, Schoenecker JG, Uitto J, Li Q
Genet Med 2022 Jan;24(1):75-86. Epub 2021 Nov 30 doi: 10.1016/j.gim.2021.08.011. PMID: 34906475Free PMC Article
Lucas C, Aranha J, da Rocha I, Sousa D
F1000Res 2020;9:9. Epub 2020 Jan 9 doi: 10.12688/f1000research.21431.1. PMID: 32742638Free PMC Article
Laube S, Moss C
Arch Dis Child 2005 Jul;90(7):754-6. doi: 10.1136/adc.2004.062075. PMID: 15970621Free PMC Article
Neldner KH
Int J Dermatol 1988 Mar;27(2):98-100. doi: 10.1111/j.1365-4362.1988.tb01280.x. PMID: 3360560
Neldner KH
Clin Dermatol 1988 Jan-Mar;6(1):1-159. doi: 10.1016/0738-081x(88)90003-x. PMID: 3359381

Clinical prediction guides

Saeidian AH, Youssefian L, Huang J, Touati A, Vahidnezhad H, Kowal L, Caffet M, Wurst T, Singh J, Snook AE, Ryu E, Fortina P, Terry SF, Schoenecker JG, Uitto J, Li Q
Genet Med 2022 Jan;24(1):75-86. Epub 2021 Nov 30 doi: 10.1016/j.gim.2021.08.011. PMID: 34906475Free PMC Article
Bartstra JW, Risseeuw S, de Jong PA, van Os B, Kalsbeek L, Mol C, Baas AF, Verschuere S, Vanakker O, Florijn RJ, Hendrikse J, Mali W, Imhof S, Ossewaarde-van Norel J, van Leeuwen R, Spiering W
Atherosclerosis 2021 May;324:18-26. Epub 2021 Mar 13 doi: 10.1016/j.atherosclerosis.2021.03.012. PMID: 33812167
Gambichler T
Arch Dermatol Res 2010 Mar;302(2):85-93. doi: 10.1007/s00403-009-1004-0. PMID: 19936772
Bergen AA, Plomp AS, Hu X, de Jong PT, Gorgels TG
Pflugers Arch 2007 Feb;453(5):685-91. Epub 2006 Apr 8 doi: 10.1007/s00424-005-0039-0. PMID: 16604369
Laube S, Moss C
Arch Dis Child 2005 Jul;90(7):754-6. doi: 10.1136/adc.2004.062075. PMID: 15970621Free PMC Article

Recent systematic reviews

Kauw F, Kranenburg G, Kappelle LJ, Hendrikse J, Koek HL, Visseren FLJ, Mali WPT, de Jong PA, Spiering W
J Neurol Sci 2017 Feb 15;373:167-172. Epub 2016 Dec 28 doi: 10.1016/j.jns.2016.12.053. PMID: 28131180
De Vilder EY, Debacker J, Vanakker OM
Int J Mol Sci 2017 Jan 25;18(2) doi: 10.3390/ijms18020240. PMID: 28125048Free PMC Article
Liaska A, Petrou P, Georgakopoulos CD, Diamanti R, Papaconstantinou D, Kanakis MG, Georgalas I
BMC Ophthalmol 2016 Jul 8;16:102. doi: 10.1186/s12886-016-0285-2. PMID: 27390837Free PMC Article

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