Pseudoxanthoma elasticum

Pseudoxanthoma elasticum is inherited in an autosomal recessive manner. Heterozygous carriers of a (likely) pathogenic variant are usually clinically unaffected, although mild or subclinical changes have occasionally been described; these do not result in a typical PXE phenotype.

The clinical diagnosis of PXE is established in a proband with characteristic skin lesions and at least one characteristic retinal finding. Characteristic findings include yellowish papules or plaques in flexural skin and angioid streaks identified on fundus examination. When ocular findings are characteristic but cutaneous findings are equivocal or subtle, identification of calcified dystrophic elastic fibres on a von Kossa (or comparable) stain of a biopsy from potentially lesional skin supports the diagnosis.

Main differential diagnoses include:

• : loose and sagging skin appears over the entire body and lacks the discrete flexural papules or plaques of PXE
• Generalised arterial calcification of infancy (GACI): severe infantile arteriopathy may overlap with the cutaneous and ocular phenotype, but GACI is very severe in children, whereas PXE is mild and often not apparent in childhood

• Establishing the molecular genetic diagnosis confirms the diagnosis and supports further medical management.
• It supports appropriate surveillance and follow-up.
• It enables targeted testing of at-risk family members, including carrier testing.

• Terry SF, Uitto J. Pseudoxanthoma Elasticum. 2020 Jun 4. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. PMID: .
• Haverkamp M, de Jong PA, Visseren FL, Spiering W. Arterial stiffness is related to a higher risk of cardiovascular events in patients with pseudoxanthoma elasticum (PXE). Vascular Medicine (London, England). 2026;31(1):19-27. doi: 10.1177/1358863X251394284. PMID: . PMCID: PMC12901643.
• Shimada BK, Pomozi V, Zoll J, Kuo S, Martin L, Le Saux O. ABCC6, Pyrophosphate and Ectopic Calcification: Therapeutic Solutions. International Journal of Molecular Sciences. 2021;22(9). doi: 10.3390/ijms22094555. PMID: . PMCID: PMC8123679.
• Kandasamy S, Shaikh N, Surve A, Kumari S, Bhayana AA, Kumar P, et al. Comprehensive review of angioid streaks. Indian Journal of Ophthalmology. 2025;73(Suppl 1):S47-S54. doi: 10.4103/IJO.IJO_812_24. PMID: . PMCID: PMC11834907.
• Orphanet. Pseudoxanthoma elasticum [Internet]. ORPHA:758. Paris: Orphanet; [cited 2026 Jun]. Available from: