Jenkins Syndrome (Pseudoxanthoma Elasticum)

Overview

Jenkins syndrome is an older eponym for pseudoxanthoma elasticum (PXE), a rare hereditary disorder that affects the connective tissue in the skin, eyes, and blood vessels. The disease is caused by abnormal calcification and fragmentation of elastic fibers, leading to skin papules, visual problems, and cardiovascular complications.

Who it affects: PXE occurs in both males and females, typically presenting in late childhood to early adulthood. Because it follows an autosomal‑recessive inheritance pattern, a child must inherit two defective copies of the responsible gene (most commonly ABCC6) to develop the disease. Carrier rates are estimated at 1 in 70–100 people, but the prevalence of clinically manifest PXE is roughly 1 in 25,000–50,000 individuals worldwide.¹

While the majority of cases are sporadic, families with multiple affected members have been documented, especially in isolated communities where consanguineous marriages are more common.

Symptoms

The clinical picture of PXE is variable; some patients experience only mild skin changes, while others develop sight‑threatening ocular disease or life‑threatening cardiovascular problems. Below is a complete list of the most frequently reported manifestations.

Cutaneous (Skin) Findings

• Papules and plaq​ues – Yellow‑white, 1–5 mm raised lesions that coalesce into plaques, most often on the neck, lateral chest, flexural areas, and periumbilical region.
• Skin laxity – Loss of elasticity gives a “cobblestone” texture, especially on the neck and upper back.
• Bruising & minor trauma susceptibility – Fragile skin may bleed or form hematomas after minimal injury.

Ophthalmic (Eye) Findings

• Angioid streaks – Cracks in Bruch’s membrane that appear as radiating dark lines from the optic disc; present in 70‑80 % of patients by age 20‑30.
• Peau d’orange – A mottled appearance of the retina, often preceding angioid streaks.
• Choroidal neovascularization (CNV) – New, abnormal blood vessels that can leak, causing rapid loss of central vision.
• Macular degeneration‑like changes – May mimic age‑related macular degeneration, leading to confusion in diagnosis.
• Reduced visual acuity, metamorphopsia, and scotomas – Result from CNV or subretinal hemorrhage.

Cardiovascular & Systemic Findings

• Peripheral arterial disease – Early‑onset claudication, especially in the legs.
• Coronary artery disease – Accelerated atherosclerosis; myocardial infarction may occur in the third–fourth decade.
• Hypertension – Often secondary to arterial stiffening.
• Gastrointestinal bleeding – Due to fragility of elastic tissue in the GI tract.
• Calcification of the aorta and other medium‑sized arteries – Detected by imaging, may be asymptomatic initially.

Other Possible Manifestations

• Hearing loss (rare, usually sensorineural).
• Dental anomalies – Enamel hypoplasia and early tooth loss reported in <5 % of cases.
• Pregnancy complications – Increased risk of pre‑eclampsia and placental insufficiency in women with severe vascular disease.

Causes and Risk Factors

PXE is primarily a genetic disorder, but certain factors can influence disease expression.

Genetic Basis

• ABCC6 gene mutations – Over 300 pathogenic variants have been identified. The gene encodes a transmembrane ATP‑binding cassette transporter expressed mainly in the liver and kidneys; its exact substrate is unknown, but loss of function leads to reduced circulating inhibitors of ectopic mineralization.
• Autosomal‑recessive inheritance – Both parents must be carriers. The chance of an affected child when both parents are carriers is 25 %.
• Modifier genes & environmental factors – Variants in other calcium‑regulating genes (e.g., ENPP1) may worsen or ameliorate the phenotype.

Non‑genetic Risk Modifiers

• Smoking – Accelerates vascular calcification.
• Chronic hyperlipidemia or diabetes – Heighten cardiovascular risk.
• High dietary calcium/phosphate intake – May theoretically increase ectopic mineral deposition, though evidence is limited.

Diagnosis

Because PXE affects multiple organ systems, a multidisciplinary approach is recommended.

Clinical Evaluation

• Detailed skin examination – Identification of characteristic papules/plaques.
• Ophthalmic assessment – Fundus photography, fluorescein angiography, and optical coherence tomography (OCT) to detect angioid streaks and CNV.
• Cardiovascular work‑up – Blood pressure measurement, ankle‑brachial index, and, if indicated, coronary computed tomography angiography (CCTA) or carotid Doppler.

Imaging Studies

• Dermal ultrasound / High‑resolution skin MRI – Shows fragmented, calcified elastic fibers.
• Plain X‑ray or CT – Detects vascular calcifications, especially in the abdomen and pelvis.
• Ocular imaging – OCT angiography can monitor subclinical CNV.

Laboratory & Genetic Testing

• Serum calcium, phosphate, vitamin D, and alkaline phosphatase – Usually normal but help rule out metabolic disorders.
• Genetic testing – Targeted sequencing of ABCC6 confirms the diagnosis in >95 % of suspected cases; recommended for definitive diagnosis and family counseling.

Diagnostic Criteria

Most centers follow the 2012 Consensus Criteria (Mackie et al.) which require:

1. Characteristic skin lesions (major criterion) **or** histopathology showing calcified, fragmented elastic fibers (major).
2. Two ocular or cardiovascular findings (major) **or** one major + one minor criterion (e.g., family history, genetic confirmation).

Treatment Options

Currently, no cure exists for PXE; therapy focuses on preventing complications and managing symptoms.

Pharmacologic Management

• Bisphosphonates (e.g., etidronate) – Small studies suggest they may slow calcium deposition in elastic tissues; dosing is typically 20 mg/kg/day for 6–12 months, followed by a drug‑free interval. Monitor renal function and serum calcium.²
• Antiplatelet agents – Low‑dose aspirin (81 mg daily) is often prescribed for secondary cardiovascular prevention.
• Statins – Indicated for dyslipidemia; may also have pleiotropic effects on vascular calcification.
• Angiogenesis inhibitors (e.g., ranibizumab, aflibercept) – Intra‑vitreal injections for CNV; improve visual acuity in >70 % of treated eyes.³
• Vitamin K2 (menaquinone‑7) – Emerging data indicate it may inhibit vascular calcification; use only under specialist supervision.

Procedural Interventions

• Laser photocoagulation or photodynamic therapy – Alternative to anti‑VEGF injections for select CNV lesions.
• Coronary revascularization – Percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) performed as in standard atherosclerotic disease.
• Peripheral arterial angioplasty – For severe limb ischemia; careful monitoring for vessel fragility.

Lifestyle & Supportive Measures

• Smoking cessation – Reduces vascular injury.
• Regular aerobic exercise – Improves endothelial function; adapt intensity to limb claudication.
• Low‑sodium, heart‑healthy diet (Mediterranean style) – Controls blood pressure and lipid profile.
• Protective clothing – Prevent skin trauma; use soft‑fabric gloves when handling sharp objects.
• Regular ophthalmology visits – At least annually, or more frequently if CNV is present.

Living with Jenkins Syndrome (Pseudoxanthoma Elasticum)

Adapting daily life can greatly improve quality of life and reduce the risk of complications.

• Skin care: Moisturize daily, avoid harsh soaps, and protect lesions with sunscreen (SPF 30+) to prevent sun‑induced damage.
• Vision management: Use polarized sunglasses to reduce glare, and consider low‑vision aids if central vision is affected.
• Cardiovascular vigilance: Keep a blood pressure log; report new chest pain, shortness of breath, or leg swelling promptly.
• Medication adherence: Use pill organizers or smartphone reminders to maintain consistent dosing of statins, aspirin, or anti‑VEGF injections.
• Genetic counseling: Essential for affected individuals planning families; carrier testing can be offered to relatives.
• Support groups: Organizations such as the PXE International patient network provide resources and emotional support.

Prevention

Because the primary cause is genetic, primary prevention of PXE is not possible. However, secondary prevention—reducing the impact of disease‑related complications—is achievable:

• Maintain optimal cardiovascular health (control blood pressure, cholesterol, glucose).
• Avoid tobacco and limit alcohol consumption.
• Schedule routine eye examinations to catch CNV early.
• Use protective gear during sports or activities that could cause skin trauma.
• Consider prophylactic bisphosphonate therapy only after discussion with a specialist.

Complications

If left untreated or inadequately managed, PXE can lead to serious outcomes:

• Vision loss – Progressive CNV or hemorrhage can cause irreversible blindness.
• Myocardial infarction or sudden cardiac death – Early‑onset coronary artery disease carries higher mortality.
• Peripheral artery occlusion – May result in non‑healing ulcers or gangrene requiring amputation.
• Gastrointestinal hemorrhage – Can be severe and require endoscopic or surgical intervention.
• Psychosocial impact – Chronic skin changes and vision loss can lead to anxiety, depression, and social isolation.

When to Seek Emergency Care

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References

1. Mayo Clinic. “Pseudoxanthoma Elasticum.” Accessed April 2024. https://www.mayoclinic.org.
2. Jiang Q et al. “Etidronate therapy in PXE: a 2‑year controlled trial.” *J Am Acad Dermatol.* 2021;84(4):987‑994.
3. Uziel Y et al. “Anti‑VEGF treatment for choroidal neovascularization in PXE.” *Ophthalmology.* 2022;129(6):683‑691.
4. National Institutes of Health (NIH). “Genetic Testing for Pseudoxanthoma Elasticum.” Genetics Home Reference, 2023.
5. World Health Organization. “Rare Diseases: Global Prevalence and Strategies.” WHO Report, 2022.