Clinical Diagnosis

Current minimal criteria for the clinical diagnosis of pseudoxanthoma elasticum (PXE) are the presence of retinal angioid streaks in combination with characteristic skin lesions showing diagnostic histopathologic findings of calcified dystrophic elastic fibers. The presence of two known PXE-causing mutations with either of the above would establish a diagnosis of PXE; the mutations alone would be presumptive evidence of PXE in an individual too young to demonstrate ocular or skin manifestations. Whether heterozygous carriers of PXE-causing mutations may have mild ocular and cutaneous findings is controversial [Sherer et al 2001, Martin et al 2008]. Molecular genetic studies of known pedigrees have shown no clinical manifestations of PXE in heterozygous carriers [Miksch et al 2005, Christen-Zach et al 2006, Plomp et al 2009, Nitschke et al 2012].

• Angioid streaks are breaks in Bruch's membrane, the elastin-rich tissue layer between the retina and the choriocapillaris. Angioid streaks radiate from the optic disk or peripapillary area in a pattern that resembles blood vessels, hence, the term 'angioid'. Angioid streaks are best observed on examination of the retina with an ophthalmoscope through a dilated pupil. Angioid streaks are readily visualized by fluorescein fundus angiography and indocyanine green (ICG) angiography, although these techniques are rarely needed for diagnosis.
• Typical skin lesions are yellowish papules, usually seen on the lateral aspect of the neck or the flexural creases, such as the antecubital fossae, axillae, groin, or popliteal fossae. With time, the papules coalesce to form plaques and the skin becomes loose and redundant.

Testing

Skin biopsy. Calcification of fragmented elastic fibers in a biopsy of lesional skin, confirmed by von Kossa or other calcium stain, is diagnostic.

Clinical testing

Inheritance is autosomal recessive; however, in a small number of cases, only one or no mutation is found. It is possible that some cases of PXE are examples of digenic inheritance, resulting from mutations in both ABCC6 and GGCX [Li et al 2009a] or hypothetically ABCC6 and ENPP1.

Table 1. Summary of Molecular Genetic Testing Used in Pseudoxanthoma Elasticum

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Gene	Test Methods	Mutations Detected	Mutation Detection Frequency 1	Test Availability
ABCC6	Sequence analysis	Sequence variants 2	~90% 3	Clinical
	Sequence analysis of select exons	Sequence variants located in select exons 4	Unknown
	Deletion / duplication analysis 5	The recurrent deletion of exons 23-29 6 and other exonic or whole-gene deletions	5%-30% depending on population

Test Availability refers to availability in the GeneTests™ Laboratory Directory. GeneReviews designates a molecular genetic test as clinically available only if the test is listed in the GeneTests™ Laboratory Directory by either a US CLIA-licensed laboratory or a non-US clinical laboratory. GeneTests does not verify laboratory-submitted information or warrant any aspect of a laboratory's licensure or performance. Clinicians must communicate directly with the laboratories to verify information.

1. The ability of the test method used to detect a mutation that is present in the indicated gene

2. Examples of mutations detected by sequence analysis may include small intragenic deletions/insertions and missense, nonsense, and splice site mutations; typically, exonic or whole-gene deletions/duplications are not detected.

3. Sequence analysis detects missense mutations, the most prevalent mutations in ABCC6 [Le Saux et al 2001, Pfendner et al 2007], as well as nonsense mutations, frameshift mutations, and small deletions and insertions, which have also been described.

4. Exons sequenced may vary by laboratory.

5. Testing that identifies deletions/duplications not readily detectable by sequence analysis of the coding and flanking intronic regions of genomic DNA; included in the variety of methods that may be used are: quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and chromosomal microarray (CMA) that includes this gene/chromosome segment. See CMA.

6. A 16.4-kb deletion involving ABCC6 exons 23-29 is a recurrent mutation found in multiple populations with varying frequency. It represents approximately 30% of alleles in the US and about 5% of alleles in Europe [Le Saux et al 2001].

Interpretation of test results. For issues to consider in interpretation of sequence analysis results, click here.

Testing Strategy

To confirm/establish the diagnosis in a proband. A commonly used testing strategy is a first-tier screen for the two most common mutations, p.Arg1141X and a deletion of exons 23-29. If only one or neither mutation is found, the next step is to screen all exons, beginning at the 3’ end with direct sequencing [Vanakker et al 2008].

Carrier testing for at-risk relatives requires prior identification of the disease-causing mutations in the family.

Note: Carriers are heterozygotes for this autosomal recessive disorder and are not at risk of developing the disorder.

Prenatal diagnosis and preimplantation genetic diagnosis (PGD) for at-risk pregnancies require prior identification of the disease-causing mutations in the family.

Note: It is the policy of GeneReviews to include in GeneReviews™ chapters any clinical uses of testing available from laboratories listed in the GeneTests™ Laboratory Directory; inclusion does not necessarily reflect the endorsement of such uses by the author(s), editor(s), or reviewer(s).

Genetically Related (Allelic) Disorders

There have been a few individuals with generalized arterial calcification of infancy (GACI) associated with biallelic mutations in ABCC6, in whom no mutations in ENPP1 could be detected [Nitschke et al 2012].

An increased risk for premature coronary artery disease among carriers of the ABCC6 mutation p.Arg1141X has been suggested [Wegman et al 2005] but not confirmed. In a recent study of over 66,000 participants (>13,000 of whom had ischemic vascular disease), heterozygosity for the p.Arg1141X mutation did not correlate with risk forischemic heart or cerebrovascular disease, stroke, or myocardial infarction [Hornstrup et al 2011].

Natural History

Pseudoxanthoma elasticum (PXE) primarily affects the skin, eye, cardiovascular system, and gastrointestinal system. Individuals with PXE most commonly present with papules in the skin and/or with angioid streaks of the retina found on routine eye examination or associated with retinal hemorrhage. Rarely, individuals may present with vascular signs and symptoms, such as gastrointestinal bleeding, angina, or intermittent claudication. The most frequent cause of morbidity and disability in PXE is reduced vision from macular hemorrhage and disciform scarring. Most affected individuals live a normal life span.

Skin. The primary skin lesion is a yellowish papule, 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, which has also been associated with acquired perforating PXE in multiparous females. The papules gradually coalesce to form plaques, and eventually the skin, especially of the neck, axilla, and groin, becomes loose and redundant. Mucous membranes can show similar lesions, most commonly the inner aspect of the lower lip and the vaginal mucosa.

Eye. The earliest ocular finding is a diffuse mottling of the fundus known as peau d'orange, generally appearing between adolescence and the late second decade. In the second and third decades, angioid streaks usually develop. These broad grayish to reddish-brown irregular lines radiate outward from the optic nerve and peripapillary region. They result from dehiscences in a mineralized Bruch's membrane, an elastin-rich layer of the choroid. Neither angioid streaks nor peau d'orange affects visual acuity; however, spontaneous subretinal neovascularization and hemorrhage can occur and lead to visual distortion (metamorphopsia) and loss of visual acuity, resulting in disciform scarring and, when the macula or fovea is involved, permanent loss of central vision.

Cardiovascular. Mineralization of the internal elastic lamina of medium-sized 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, or angina or myocardial infarction (coronary arteries), small strokes (cerebrovascular arteries), intestinal angina (celiac or mesenteric arteries), and renovascular hypertension (renal arteries). At least one small series suggested an increased incidence of mitral valve prolapse in individuals with PXE [Lebwohl et al 1982]. However, this has yet to be confirmed by larger prospective controlled studies.

Gastrointestinal. The most common site of bleeding is the upper gastrointestinal tract, particularly the stomach. The characteristic yellow mucosal lesions of PXE can be seen on gastroscopy. The cause of bleeding is not well understood; one theory is that it may begin with superficial bleeding from erosive gastritis, but 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. Bleeding may be difficult to control without surgery [Dalle & Geboes 2002].

Pregnancy. Most women with PXE have normal pregnancies: PXE is not associated with markedly increased fetal loss or adverse reproductive outcomes. The incidence of gastric bleeding and retinal complications (<1%) is lower than previously thought [Bercovitch et al 2004].

Genotype-Phenotype Correlations

To date, no genotype-phenotype correlations are known [Pfendner et al 2007].

Nomenclature

Earlier reports sometimes referred to PXE as Grondblad-Strandberg syndrome.

Prevalence

The exact prevalence is unknown. Published reports estimate prevalence from 1:25,000 to 1:100,000.

An increased risk for PXE is seen in a few populations including the Afrikaners in South Africa, who display a founder effect [Le Saux et al 2002].

Evaluations Following Initial Diagnosis

To establish the extent of disease in an individual diagnosed with pseudoxanthoma elasticum (PXE), the following assessments are recommended:

• Complete skin examination, including a biopsy of potentially lesional skin from the axilla or neck. A von Kossa or similar histologic stain for calcium should be done on the biopsy to confirm the diagnosis, although PXE can be strongly suspected on skin biopsy even without special stains.
• Complete dilated eye examination by a retinal specialist, particularly looking for peau d'orange and angioid streaks. A fluorescein angiogram may be necessary to confirm the diagnosis.
• Baseline cardiovascular examination with periodic follow-up for individuals with pseudoxanthoma elasticum (PXE), including (as clinically indicated based on age, physical findings, and exercise level):
  • Echocardiography
  • Cardiac stress testing
  • Doppler evaluation of peripheral vasculature

Treatment of Manifestations

No specific treatment for PXE exists.

Management of PXE requires coordinated input from a multidisciplinary team of specialists including a dermatologist, primary care physician, ophthalmologist, cardiologist, vascular surgeon, plastic surgeon, genetics professional, and nutritionist. Support groups can benefit affected individuals and their families by providing accurate information and education and reducing isolation.

Current treatment for macular degeneration, especially the intraocular injection of anti-angiogenic drugs, also appears to be effective in PXE [Finger et al 2011]. A retinal specialist should be consulted immediately when the individual experiences any distortion in vision.

Surgical or radiologic intervention may be indicated for gastrointestinal bleeding, severe peripheral vascular disease (if correctable), and the improvement of changes of the skin of the face, neck, axilla, and groin that are of cosmetic concern. Although wound healing seems to be uncomplicated in PXE, cosmetic acceptability of surgery involving the skin is less predictable, although generally good [Viljoen et al 1990].

Prevention of Primary Manifestations

Weight control, avoidance of smoking, and aggressive management of hypertension and lipid disorders may reduce the risk of vascular complications by reducing the risk of comorbidity resulting from atherosclerosis. However, reduction in risk resulting from these measures has not been confirmed in controlled studies.

Prevention of Secondary Complications

Individuals with PXE who have coexistent mitral valve prolapse should have antibiotic prophylaxis for dental, gastrointestinal, and genitourinary procedures.

Surveillance

The following are appropriate:

• Regular examination by an ophthalmologist with expertise in retinal disease. Affected individuals benefit from learning to use the Amsler grid to monitor for central visual disturbances.
• Regular physical examination with specific attention to the cardiovascular system
• Monitoring by the affected individual for black tarry stool
• Periodic monitoring of serum lipid concentrations

Agents/Circumstances to Avoid

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.

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.

Aspirin and nonsteroidal anti-inflammatory medications should be avoided whenever possible to reduce the risk of gastrointestinal bleeding.

Evaluation of Relatives at Risk

See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.

Pregnancy Management

In the series of Bercovitch et al [2004], there was no statistically significant effect of gravidity on the severity of skin, eye, cardiac, or peripheral vascular manifestations of PXE in women over 40. In addition, women over 40 with PXE who had been pregnant did not have more severe skin, cardiac, ocular, or vascular manifestations of PXE than those who had never been pregnant. Except for the consequences of severe maternal gastrointestinal hemorrhage, which appears to be uncommon, PXE has no known significant effect on the fetus. Retinal examination during pregnancy and prompt attention to any visual symptoms are advised.

Therapies Under Investigation

Based on animal studies [Larusso et al 2009, Li et al 2009c], magnesium supplementation has been proposed as a treatment to prevent progression of elastic tissue mineralization in PXE. A randomized placebo-controlled clinical trial to study the effect of magnesium oxide supplementation is beginning in 2012.

Search ClinicalTrials.gov for access to information on clinical studies for a wide range of diseases and conditions.

Other

It has been reported that high calcium intake in adolescence may correlate with the overall severity of PXE [Renie et al 1984]; however, this has never been confirmed by prospective controlled studies and thus remains unproven and controversial.

The AREDS study for macular degeneration suggested that a regimen of antioxidant vitamins could prove beneficial in that disease [Clemons et al 2004]. While it is possible that this could also be the case for PXE, it has not been reported and remains unproven.

Genetics clinics, staffed by genetics professionals, provide information for individuals and families regarding the natural history, treatment, mode of inheritance, and genetic risks to other family members as well as information about available consumer-oriented resources. See the GeneTests Clinic Directory.

Mode of Inheritance

Pseudoxanthoma elasticum (PXE) is inherited in an autosomal recessive manner.

Risk to Family Members

Parents of the proband

• The parents of an affected individual are obligate heterozygotes and therefore carry one mutant allele.
• It is not known at this time to what degree parents who are carriers of a mutant allele causing PXE are at risk for some manifestations of the disorder. It has been reported that the presence of calcified elastic fibers on biopsy of lesional skin and limited ocular and cutaneous signs of PXE in parents may be consistent with the heterozygous carrier state [Sherer et al 2001], but the individuals in that study did not have molecular genetic studies, so it was not conclusive.
• Parents of a probands can undergo ocular and skin examination looking for signs of PXE, but skin biopsies and/or genetic testing would not be indicated unless the diagnosis of PXE was suspected in a presumed obligate carrier.

Sibs of the proband

• At conception, each sib of an individual with autosomal recessive PXE has 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.
• Once an at-risk sib is known to be unaffected, the chance of his/her being a carrier is 2/3.
• Most relatives have peau d'orange and/or angioid streaks by the first or second decade if they are affected. Heterozygotes (carriers) may have minimal clinical findings.

Offspring of the proband. The offspring of an individual with autosomal recessive PXE are obligate heterozygotes (carriers) for a mutant allele causing PXE (see Heterozygotes).

Other family members of the proband. Each sib of the proband's parents has a 50% chance of being a carrier.

Heterozygotes (carriers) are usually asymptomatic. Whether heterozygous carriers of an ABCC6 mutation may have mild ocular and cutaneous findings is controversial [Bacchelli et al 1999, Sherer et al 2001, Martin et al 2008]. No clinical manifestations of PXE have been observed in molecularly diagnosed heterozygous carriers [Miksch et al 2005, Christen-Zach et al 2006, Plomp et al 2009].

Carrier Detection

Carrier testing for at-risk family members is available on a clinical basis once the mutations have been identified in the proband.

Related Genetic Counseling Issues

Evidence in support of autosomal recessive inheritance pattern. Although early literature on PXE suggests autosomal dominant inheritance based on the observation of two-generation familial occurrence of PXE, these cases have been shown to be pseudodominant [Bergen 2006, Ringpfeil et al 2006]. No three-generation affected pedigrees have been reported. Autosomal dominant inheritance has not been confirmed.

Pedigree analysis, skin biopsy, retinal examination, and molecular genetic studies may fail to establish the mode of inheritance or to distinguish a carrier from an affected individual, but these situations are the exception [Martin et al 2008].

Family planning

• The optimal time for determination of genetic risk, clarification of carrier status, and discussion of the availability of prenatal testing is before pregnancy.
• 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.

DNA banking is the storage of DNA (typically extracted from white blood cells) for possible future use. Because it is likely that testing methodology and our understanding of genes, mutations, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals. See for a list of laboratories offering DNA banking.

Prenatal Testing

Prenatal diagnosis for pregnancies at increased risk is possible by analysis of DNA extracted from fetal cells obtained by amniocentesis usually performed at approximately 15 to 18 weeks’ gestation or chorionic villus sampling (CVS) at approximately ten to 12 weeks’ gestation. The disease-causing mutations in the family must have been identified before prenatal testing can be performed.

Note: Gestational age is expressed as menstrual weeks calculated either from the first day of the last normal menstrual period or by ultrasound measurements

Preimplantation genetic diagnosis (PGD) may be available for families in which the disease-causing mutations have been identified in an affected family member. For laboratories offering PGD, see .

Note: It is the policy of GeneReviews to include in GeneReviews™ chapters any clinical uses of testing available from laboratories listed in the GeneTests™ Laboratory Directory; inclusion does not necessarily reflect the endorsement of such uses by the author(s), editor(s), or reviewer(s).

Literature Cited

1. Bacchelli B, Quaglino D, Gheduzzi D, Taparelli F, Boraldi F, Trolli B, Le Saux O, Boyd CD, Ronchetti IP. Identification of heterozygote carriers in families with a recessive form of pseudoxanthoma elasticum (PXE). Mod Pathol. 1999;12:1112–23. [PubMed: 10619263]
2. 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. Dermatology. 2005;210:60–3. [PubMed: 15604549]
3. Bercovitch L, Leroux T, Terry S, Weinstock MA. Pregnancy and obstetrical outcomes in pseudoxanthoma elasticum. Br J Dermatol. 2004;151:1011–8. [PubMed: 15541079]
4. Bergen AA. Pseudoxanthoma elasticum: the end of the autosomal dominant segregation myth. J Invest Dermatol. 2006;126:704–5. [PubMed: 16541094]
5. Christen-Zäch S, Huber M, Struk B, Lindpaintner K, Munier F, Panizzon RG, Hohl D. Pseudoxanthoma elasticum: evaluation of diagnostic criteria based on molecular data. Br J Dermatol. 2006;155:89–93. [PubMed: 16792757]
6. Clemons TE, Kurinij N, Sperduto RD. AREDS Research Group; Associations of mortality with ocular disorders and an intervention of high-dose antioxidants and zinc in the Age-Related Eye Disease Study: AREDS Report No. 13. Arch Ophthalmol. 2004;122:716–26. [PMC free article: PMC1473208] [PubMed: 15136320]
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8. Finger RP, Charbel Issa P, Schmitz-Valckenberg S, Holz FG, Scholl HN. Long-term effectiveness of intravitreal bevacizumab for choroidal neovascularization secondary to angioid streaks in pseudoxanthoma elasticum. Retina. 2011;31:1268–78. [PubMed: 21386758]
9. Hornstrup LS, Tybjærg-Hansen A, Haase CL, Nordestgaard BG, Sillesen H, Grande P, Frikke-Schmidt R. Heterozygosity for R1141X in ABCC6 and risk of ischemic vascular disease. Circ Cardiovasc Genet. 2011;4:534–41. [PubMed: 21831958]
10. LaRusso J, Li Q, Jiang Q, Uitto J. Elevated dietary magnesium prevents connective tissue mineralization in a mouse model of pseudoxanthoma elasticum (Abcc6(-/-)). J Invest Dermatol. 2009;129:1388–94. [PMC free article: PMC2879622] [PubMed: 19122649]
11. Le Saux O, Beck K, Sachsinger C, Silvestri C, Treiber C, Göring HH, Johnson EW, De Paepe A, Pope FM, Pasquali-Ronchetti I, Bercovitch L, Marais AS, Viljoen DL, Terry SF, Boyd CD. A spectrum of ABCC6 mutations is responsible for pseudoxanthoma elasticum. Am J Hum Genet. 2001;69:749–64. [PMC free article: PMC1226061] [PubMed: 11536079]
12. 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. Hum Genet. 2002;111:331–8. [PubMed: 12384774]
13. Lebwohl MG, Distefano D, Prioleau PG, Uram M, Yannuzzi LA, Fleischmajer R. Pseudoxanthoma elasticum and mitral-valve prolapse. N Engl J Med. 1982;307:228–31. [PubMed: 7088072]
14. Li Q, Grange DK, Armstrong NL, Whelan AJ, Hurley MY, Rishavy MA, Hallgren KW, Berkner KL, Schurgers LJ, Jiang Q, Uitto J. Mutations in the GGCX and ABCC6 genes in a family with pseudoxanthoma elasticum-like phenotypes. J Invest Dermatol. 2009a;129:553–63. [PMC free article: PMC2900916] [PubMed: 18800149]
15. Li Q, Jiang Q, Pfendner E, Váradi A, Uitto J. Pseudoxanthoma elasticum: clinical phenotypes, molecular genetics and putative pathomechanisms. Exp Dermatol. 2009b;18:1–11. [PMC free article: PMC3349969] [PubMed: 19054062]
16. Li Q, Larusso J, Grand-Pierre AE, Uitto J. Magnesium carbonate-containing phosphate binder prevents connective tissue mineralization in Abcc6(-/-) mice-potential for treatment of pseudoxanthoma elasticum. Clin Transl Sci. 2009c;2:398–404. [PMC free article: PMC3005270] [PubMed: 20443931]
17. Martin L, Maître F, Bonicel P, Daudon P, Verny C, Bonneau D, Le Saux O, Chassaing N. Heterozygosity for a single mutation in the ABCC6 gene may closely mimic PXE: consequences of this phenotype overlap for the definition of PXE. Arch Dermatol. 2008;144:301–6. [PubMed: 18347285]
18. 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. Hum Mutat. 2005;26:235–48. [PubMed: 16086317]
19. 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. Am J Hum Genet. 2012;90:25–39. [PMC free article: PMC3257960] [PubMed: 22209248]
20. 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. J Med Genet. 2007;44:621–8. [PMC free article: PMC2597973] [PubMed: 17617515]
21. Plomp AS, Bergen AA, Florijn RJ, Terry SF, Toonstra J, van Dijk MR, de Jong PT. Pseudoxanthoma elasticum: Wide phenotypic variation in homozygotes and no signs in heterozygotes for the c.3775delT mutation in ABCC6. Genet Med. 2009;11:852–8. [PubMed: 19904211]
22. Renie WA, Pyeritz RE, Combs J, Fine SL. Pseudoxanthoma elasticum: high calcium intake in early life correlates with severity. Am J Med Genet. 1984;19:235–44. [PubMed: 6507474]
23. Ringpfeil F, McGuigan K, Fuchsel L, Kozic H, Larralde M, Lebwohl M, Uitto J. Pseudoxanthoma elasticum is a recessive disease characterized by compound heterozygosity. J Invest Dermatol. 2006;126:782–6. [PubMed: 16410789]
24. Sherer DW, Bercovitch L, Lebwohl M. Pseudoxanthoma elasticum: significance of limited phenotypic expression in parents of affected offspring. J Am Acad Dermatol. 2001;44:534–7. [PubMed: 11209132]
25. Uitto J, Bercovitch L, Terry SF, Terry PF. Pseudoxanthoma elasticum: progress in diagnostics and research towards treatment : Summary of the 2010 PXE International Research Meeting. Am J Med Genet A. 2011;155A:1517–26. [PMC free article: PMC3121926] [PubMed: 21671388]
26. Vanakker OM, Leroy BP, Coucke P, Bercovitch LG, Uitto J, Viljoen D, Terry SF, Van Acker P, Matthys D, Loeys B, De Paepe A. Novel clinico-molecular insights in pseudoxanthoma elasticum provide an efficient molecular screening method and a comprehensive diagnostic flowchart. Hum Mutat. 2008;29:205. [PubMed: 18157818]
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28. Wegman JJ, Hu X, Tan H, Bergen AA, Trip MD, Kastelein JJ, Smulders YM. Patients with premature coronary artery disease who carry the ABCC6 R1141X mutation have no Pseudoxanthoma Elasticum phenotype. Int J Cardiol. 2005;100:389–93. [PubMed: 15837081]

Author Notes

Sharon Terry, Founding Executive Director of PXE International, manages the 36-lab PXE International Research consortium, 56 offices worldwide, and the PXE International Registry and BioBank. She is also President & CEO of Genetic Alliance, a coalition of more than 1200 disease advocacy organizations representing 1500 diseases. She is the co-founder of the Genetic Alliance Registry and BioBank.

Lionel Bercovitch, MD, Medical Director of PXE International and Professor of Dermatology and Director of Pediatric Dermatology at Warren Alpert Medical School of Brown University, coordinates all of the research that PXE International initiates and oversees the production of educational materials for affected individuals and health professionals.

Author History

Lionel G Bercovitch, MD (2001-present)
Charles D Boyd, PhD; University of Hawaii (2001-2006)
Sharon F Terry, MA (2001-present)

Revision History

• 14 June 2012 (me) Comprehensive update posted live
• 2 April 2007 (st) Revision: Molecular Genetic Testing - targeted mutation analysis changed to deletion analysis
• 11 December 2006 (me) Comprehensive update posted to live Web site
• 5 November 2003 (me) Comprehensive update posted to live Web site
• 14 March 2002 (st) Author revision
• 5 June 2001 (me) Review posted to live Web site
• September 2000 (st) Original submission