Questions and Answers
What is the typical age of diagnosis for individuals with a positive family history of PXE?
Which of the following best describes the skin findings in patients with PXE?
What is the heritable nature of Grönblad-Strandberg syndrome classified as?
Which feature is likely to be highly specific for PXE prior to 30 years of age?
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In PXE, what type of system involvement can patients exhibit?
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What is the estimated incidence of cutis laxa in live births?
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Which is true regarding the skin elasticity in patients with cutis laxa?
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Which of the following describes a common feature in individuals with autosomal dominant cutis laxa?
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What percentage success is estimated for detecting mutations in patients with AR form of cutis laxa Type I?
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What is one notable characteristic of the viscoelastic nature of skin in patients with cutis laxa compared to normal patients?
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Study Notes
Grönblad-Strandberg Syndrome (PxE)
- Also known as Grönblad-Strandberg syndrome; a hereditary ectopic mineralization disorder.
- Characterized by progressive calcium hydroxyapatite deposition on elastic tissues.
- Prevalence estimated at 1 in 25,000 to 100,000 individuals; likely underdiagnosed.
- Classified as an autosomal recessive disorder with documented pseudodominance.
Clinical Presentation
- Average diagnosis age: 8 to 12 years, especially in those with a family history.
- Clinical heterogeneity observed; some families have members with isolated symptoms.
- Dermatological signs include yellowish, flat-topped papules commonly located in skin folds.
- Skin changes may be subtle initially, becoming more prominent with age, leading to "plucked chicken skin."
Ocular Manifestations
- Angioid streaks are observed in 87% of patients; these are radial, curvilinear extensions associated with retinal damage.
- Commonly appear in the third or fourth decade; earliest recorded cases occurred in patients as young as 10.
- Visual acuity is often unaffected; late complications may lead to significant vision loss.
Vascular Complications
- GI and renal vasculature frequently exhibit early signs of damage, often highlighting acute hemorrhages.
- Hypertension and GI bleeding commonly arise, particularly before the age of 30.
- Late-stage complications include cerebrovascular accidents and myocardial infarction; documented cases of significant coronary artery disease in adolescents.
Genetic Factors
- Primary mutation identified in the ABCC6 gene on chromosome 16p13.1.
- Common mutations: R1141X (predominant in Europe) and ABCC6del23-29 (notable in U.S. populations).
- ABCC6 protein primarily expressed in liver and kidney; deficiency leads to dysregulation of mineralization.
Additional Genetic Considerations
- Phenotypic diversity suggests other genes or environmental factors may contribute.
- Associations reported with polymorphisms in the SPP1 gene and mutations in GGCX, linked to coagulation deficiencies.
Diagnosis and Investigative Approaches
- Histological confirmation through skin biopsy shows characteristic broken curls of elastic fibers.
- Imaging techniques may reveal vascular calcification; ultrasonography identifies renal arteries' echogenicity patterns.
Treatment and Management Strategies
- There is currently no cure; management emphasizes symptomatic relief and complications prevention.
- Lifestyle modifications include avoiding contact sports and maintaining a healthy diet with cholesterol control.
- Potential treatments under investigation include bisphosphonates and dietary supplements like magnesium.
- Regular evaluations by specialists in cardiology and ophthalmology are essential.
Prognosis and Quality of Life
- Patients may face complications that impair quality of life, such as visual impairment and vascular issues.
- Increased awareness and multidisciplinary care can mitigate some effects of the disease.
Cutis Laxa Overview
- Cutis laxa manifests in autosomal dominant (AD), autosomal recessive (AR), and X-linked forms, with recessive types being the most prevalent.
- Estimated incidence of cutis laxa is 1 in 1,000,000 live births; few hundred cases recorded globally.
- Historical identification of molecular causes in cutis laxa patients has been limited, though advancements in next-generation sequencing are improving diagnosis rates.
Clinical Presentation
- Clinically, skin in cutis laxa is inelastic, appearing pendulous, soft, and loose at birth.
- Skin hyperextensibility exists, but normal shape is poorly regained after stretching.
- Patients exhibit facial features reminiscent of bloodhounds: loose skin on the face, neck, shoulders, and thighs, often presenting aged appearance in youth.
- Unlike Ehlers-Danlos syndrome (EDS), patients typically lack skin fragility and abnormal scarring.
Types of Cutis Laxa
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Autosomal Dominant Cutis Laxa (ADCL)
- Affects all ages, generally with benign course and near-normal life expectancy.
- Notable facial features include beaked nose, long philtrum, high forehead, and large ears.
- Less internal involvement than other forms.
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X-linked Cutis Laxa
- Primarily affects males; associated with occipital horn syndrome and Menkes disease.
- Clinical manifestations begin around 2-3 months, including hypotonia and distinctive facial features like inverted eyelids and beaked noses.
- Characterized by feeding difficulties, developmental delays, and potential mortality in early years.
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Autosomal Recessive Cutis Laxa (ARCL)
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Type 1 (ARCL1)
- Highly variable; severe cases present emphysema, hernias, pulmonary artery stenosis, and visceral organ involvement.
- Cutaneous findings often severe with significant skin laxity.
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Type 2 (ARCL2)
- Distinct clinical findings categorized by N- and O-linked glycosylation defects.
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Subtypes:
- ARCL2A: Caused by ATP6V0A2 mutations, shows variability in symptoms and developmental delays.
- ARCL2B: Caused by PYCR mutations; presents with severe wrinkling and common CNS abnormalities like agenesis of the corpus callosum.
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Genetic Basis
- Cutis laxa involves mutations affecting elastic fiber synthesis, stability, or degradation impacting skin elasticity.
- Essential components of elastic fibers include elastin and microfibrillar sheaths, primarily composed of fibrillin.
- Specific gene mutations (e.g., in elastin, fibulin 4, and fibulin 5) lead to abnormal elastic fiber formation, contributing to clinical phenotypes.
- ARCL1 is often associated with mutations in fibulin genes, leading to severe manifestations, particularly cardiovascular complications.
Complications and Management
- Internal organ involvement can occur in various forms of cutis laxa, complicating clinical management.
- Early intervention, such as copper replacement therapy in specific subtypes of X-linked cutis laxa, may improve outcomes.
- Patients often experience a spectrum of symptoms, requiring multidisciplinary care to address diverse clinical needs and improve quality of life.
Summary of Clinical Features
- Distinctive facial characteristics include loose skin, unique nasal features, and potential neurological impairments.
- Joint laxity and hypermobility can impact mobility and overall function, leading to further complications over time.
- Significant variability exists in the severity and manifestations of cutis laxa across its different forms and genetic subtypes.
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Description
This quiz explores Grönblad-Strandberg syndrome, a rare ectopic mineralization disorder. Learn about its characteristics, prevalence, genetic aspects, and how it relates to pseudoxanthoma elasticum. Understand the implications of being a heterozygous carrier in this hereditary condition.
