Pseudoxanthoma Elasticum

Clinical Characteristics
Ocular Features: 

Breaks in Bruch membrane lead to the classic non-diagnostic ocular sign in this disease known as angioid streaks.  These are typically bilateral, reddish-brown curvilinear bands that vaguely resemble a vascular pattern seen most commonly in the posterior pole radiating from the peripapillary area.  They typically have their onset after the skin lesions appear.  The fundus may also have areas of yellow mottling temporal to the fovea suggestive of an orange peel surface.  These are sometimes labeled 'peau d'orange' and their appearance frequently precedes the appearance of angioid streaks.  Optic disc drusen are said to occur 20-50 times more frequently than in the general population and may be apparent before the appearance of angioid streaks.  A significant proportion of patients have atrophy of the RPE and outer retina, especially those with early onset and rapid progression of the disease.

The major threat to vision comes from the formation of subretinal neovascular nets which often bleed resulting in secondary scarring and fibrosis.  These frequently involve the central macula which is why central vision is primarily impacted and peripheral vision usually remains normal.  Macular involvement is evident at a mean age of 44 years and the majority of patients are visually handicapped by the age of 52 years.

Systemic Features: 

The skin has characteristic changes of several types due to defective elastin.  It is often lax and redundant with localized plaques of hyperkeratotic papules giving the typical 'plucked chicken' appearance.  The latter are typically seen in the skin of the neck, in inguinal folds and in the popliteal and antecubital spaces.  These may have their onset in childhood but sometimes later.  They are generally asymptomatic and primarily of cosmetic importance.  The oral, rectal, and vaginal mucosa may also be involved.  Focal deposits of calcium are often seen.

Vascular disease secondary to calcification of elastic media and intima are responsible for the major health problems in this disease but they usually are not evident until later in life.  Hemorrhage or occlusion often results.  At least 10% of individuals with this disease experience a gastrointestinal hemorrhage at some point in their lives and this can be life-threatening.  Intermittent claudication can be incapacitating.  Coronary artery disease is frequently a symptom.  Occlusive disease of the renal arteries can result in hypertension.  Malfunction of heart valves, especially the mitral valve, is common.


This is an autosomal recessive disorder caused by mutations in the ABCC6 gene (16p13.1).  Females are affected nearly twice as often as males.  Some heterozygotes have minor manifestations of the disease but the full clinical picture is only seen in homozygotes.

Rare variant mutations in the ABCC6 gene may cause typical ocular changes without systemic manifestations.

Treatment Options: 

Choroidal neovascularization should be treated.  Intravitreal injections of ranibizumab may be beneficial as a prophylactic measure for the preservation of central vision.  GI bleeds require prompt and vigorous treatment and cardiac valves sometimes require repair.  Redundant skin can be surgically removed.  Patients should avoid contact sports and activities requiring heavy lifting or straining.  Antibiotic prophylaxis should be considered for patients with heart valve disease before undergoing procedures.

Article Title: 


Fukumoto T, Iwanaga A, Fukunaga A, Wataya-Kaneda M, Koike Y, Nishigori C, Utani A. First genetic analysis of atypical phenotype of pseudoxanthoma elasticum with ocular manifestations in the absence of characteristic skin lesions. J Eur Acad Dermatol Venereol. 2017 Oct 12. doi: 10.1111/jdv.14637. [Epub ahead of print].

PubMedID: 29024034

Gliem M, Muller 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. Invest Ophthalmol Vis Sci. 2016 Jun 1;57(7):3323-3330.

PubMedID: 27367499

Orssaud C, Roche O, Dufier JL, Germain DP. Visual Impairment in Pseudoxanthoma Elasticum: A Survey of 40 Patients. Ophthalmic Genet. 2014 Apr 21. [Epub ahead of print].

PubMedID: 24749718

Gliem M, Zaeytijd JD, Finger RP, Holz FG, Leroy BP, Charbel Issa P. An update on the ocular phenotype in patients with pseudoxanthoma elasticum. Front Genet. 2013.  Epub 2013 Apr 4.

PubMedID: 23577018

Finger RP, Charbel Issa P, Hendig D, Scholl HP, Holz FG. Monthly Ranibizumab for Choroidal Neovascularizations Secondary to Angioid Streaks in Pseudoxanthoma Elasticum: A One-Year Prospective Study. Am J Ophthalmol. 2011 Jun 24. [Epub ahead of print] PubMed PMID: 21704964.

PubMedID: 21704964

Plomp AS, Toonstra J, Bergen AA, van Dijk MR, de Jong PT. Proposal for updating the pseudoxanthoma elasticum classification system and a review of the clinical findings. Am J Med Genet A. 2010 Apr;152A(4):1049-58.

PubMedID: 20358627

Zarbock R, Hendig D, Szliska C, Kleesiek K, Gotting C. Vascular endothelial growth factor gene polymorphisms as prognostic markers for ocular manifestations in pseudoxanthoma elasticum. Hum Mol Genet. 2009 Sep 1;18(17):3344-51.

PubMedID: 19483196

Bergen AA. Pseudoxanthoma elasticum: the end of the autosomal dominant segregation myth. J Invest Dermatol. 2006 Apr;126(4):704-5.

PubMedID: 16541094