Rare Cardiology News

Disease Profile

Sneddon syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Adult

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ICD-10

I77.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Sneddon's syndrome; Livedo reticularis and cerebrovascular accidents; Cerebro-vascular lesions and livedo reticularis;

Categories

Blood Diseases; Congenital and Genetic Diseases; Nervous System Diseases;

Summary

Sneddon syndrome is a rare, progressive condition that affects blood vessels. It is primarily characterized by livedo reticularis (net-like patterns of discoloration on the skin) and neurological abnormalities.[1][2] Symptoms may include transient ischemic attacks (mini-strokes) and strokes; headache; dizziness; high blood pressure; and heart disease.[1][2] Reduced blood flow to the brain may cause reduced intellectual ability, memory loss, personality changes, and/or other neurological symptoms. The cause of Sneddon syndrome is often unknown, but it is sometimes associated with an autoimmune disease. Most cases are sporadic but some familial cases with autosomal dominant inheritance have been reported. Some researchers separate Sneddon syndrome into two different types depending on whether an underlying cause has been identified (primary versus idiopathic), while others suggest a classification based on whether certain symptoms of autoimmune disease are present or not (aPL-positive versus aPL negative).[1] Treatment usually involves anticoagulation (blood-thinning) with warfarin, and/or the use of other medications.[2]

Symptoms

Sneddon syndrome is primarily characterized by livedo reticularis (net-like patterns of discoloration on the skin) and neurological abnormalities.[1][2] The average age of onset of neurological symptoms is 39 years, though the livedo generally occurs up to 10 years earlier (sometimes since childhood).[3]

The type of livedo reticularis that occurs is called livedo racemosa, a generalized and persistent form of livedo. It may affect the arms and legs, buttocks, trunk, face, hands, and feet.[3] Some affected individuals also have signs of Raynaud’s phenomenon and/or widespread, mottled-purple discoloration on the body.[3]

Neurological symptoms may include transient ischemic attacks (mini-strokes) and strokes; headache; and dizziness.[1][2] Reduced blood flow to the brain may cause reduced intellectual ability, memory loss, psychiatric disturbances, personality changes, and/or other neurological symptoms.[1][3] Concentration, attention, memory, visual perception and visuospatial construction are the most commonly described cognitive impairments. Dementia ultimately occurs in many affected people. Rarer neurological symptoms include seizures, chorea, and myelopathies (disorders of the spinal cord).[3]

Other signs and symptoms may include high blood pressure, heart disease, ophthalmologic (eye) complications, and impaired renal (kidney) function.[3]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Arterial stenosis
Narrowing of an artery
0100545
Behavioral abnormality
Behavioral changes
Behavioral disorders
Behavioral disturbances
Behavioral problems
Behavioral/psychiatric abnormalities
Behavioural/Psychiatric abnormality
Psychiatric disorders
Psychiatric disturbances

[ more ]

0000708
Cutis marmorata
0000965
Memory impairment
Forgetfulness
Memory loss
Memory problems
Poor memory

[ more ]

0002354
Migraine
Intermittent migraine headaches
Migraine headache
Migraine headaches

[ more ]

0002076
Thromboembolic stroke
0001727
Vertigo
Dizzy spell
0002321
30%-79% of people have these symptoms
Amaurosis fugax
0100576
Dementia
Dementia, progressive
Progressive dementia

[ more ]

0000726
Developmental regression
Loss of developmental milestones
Mental deterioration in childhood

[ more ]

0002376
Hemiparesis
Weakness of one side of body
0001269
Hypertension
0000822
Motor delay
0001270
Muscle weakness
Muscular weakness
0001324
Visual field defect
Partial loss of field of vision
0001123
5%-29% of people have these symptoms
Antiphospholipid antibody positivity
0003613
Aphasia
Difficulty finding words
Losing words
Loss of words

[ more ]

0002381
Chorea
0002072
Intracranial hemorrhage
Bleeding within the skull
0002170
Nephropathy
0000112
Seizure
0001250
Tremor
0001337
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance
0000007
Dysarthria
Difficulty articulating speech
0001260
Facial palsy
Bell's palsy
0010628
Headache
Headaches
0002315
Hemiplegia
Paralysis on one side of body
0002301
Mental deterioration
Cognitive decline
Cognitive decline, progressive
Intellectual deterioration
Progressive cognitive decline

[ more ]

0001268
Progressive
Worsens with time
0003676
Sporadic
No previous family history
0003745
Stroke
0001297

Cause

The underlying cause of Sneddon syndrome is not well-understood. About 50% of cases are idiopathic (of unknown cause). In some cases, it is associated with autoimmune diseases such as systemic lupus erythematosus, antiphospholipid syndrome, Behçet disease, or mixed connective tissue disease.[2]

Genetic factors are thought to play a role in the development of Sneddon syndrome, as familial cases have been reported.[2] In one family, a mutation in the CECR1 gene was identified as the cause of the condition.[4] Mutations in this gene have been found to cause adenosine deaminase 2 deficiency, a condition that also causes livedo racemosa (and other symptoms) and has earlier onset than Sneddon syndrome.

The signs and symptoms of the condition are caused by excessive growth of the inner surface of blood vessels (endothelium), leading to occlusion of the arteries with impaired blood flow and clotting.[2]

Diagnosis

The main criteria for a diagnosis of Sneddon syndrome are general livedo racemosa with characteristic findings on skin biopsy, and focal neurological deficits. Supportive criteria include a history of transient ischemic attacks or stroke and evidence of small bright foci on T2-weighted MRI.[3]

Anyone suspected to have Sneddon syndrome may undergo:[3][2]

  • blood tests (see below)
  • a thorough cardiovascular (heart) evaluation;
  • brain MRI which may reveal white matter changes, infarcts, microbleeds or atrophy;
  • cerebral angiography (abnormal in up to 75% of patients); and
  • skin biopsy, which may reveal occlusion of arterioles by proliferation of the inner lining (characteristic of Sneddon syndrome)

Blood tests may screen for:[3][2]

Treatment

The optimal management of Sneddon syndrome has not been established, and controlled trials have not yet been performed.[3] Currently, the most widely accepted treatment is anticoagulation with warfarin. Some suggest that aPL-negative patients should follow a less aggressive approach consisting of antiplatelet therapy with aspirin, while others recommend warfarin with a higher international normalized ratio target.[2]

Angiotensin-converting enzyme (ACE) inhibitors have been suggested to reduce endothelial proliferation (growth of the inside lining of the vessels), and prostaglandin to improve blood flow and gas exchange in small vessels (microvascular perfusion).[2] Abstaining from smoking and abstaining from using estrogen oral contraceptives may prevent or decrease the severity of neurological symptoms.[3]

While the use of immunosuppressive therapy appears generally ineffective, there are data indicating that rituximab may be effective in aPL-positive patients.[2]

Additional research exploring the underlying causes of Sneddon syndrome may identify treatment options based on the cause in each affected person.[3]

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

    Organizations Providing General Support

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

      • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

        In-Depth Information

        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Sneddon syndrome. Click on the link to view a sample search on this topic.

          References

          1. Berlit P. Sneddon Syndrome. National Organization for Rare Disorders (NORD). 2016; https://rarediseases.org/rare-diseases/sneddon-syndrome/.
          2. Berlit P. Sneddon syndrome. Orphanet. March, 2015; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=820.
          3. Wu S, Xu Z, Liang H. Sneddon’s syndrome: a comprehensive review of the literature. Orphanet J Rare Dis. 2014; 9:215:https://ojrd.biomedcentral.com/articles/10.1186/s13023-014-0215-4.
          4. Kniffin CL. Sneddon syndrome. OMIM. August 4, 2014; https://www.omim.org/entry/182410.
          5. Bayrakli F, Erkek E, Kurtuncu M, Ozgen S. Intraventricular hemorrhage as an unusual presenting form of Sneddon syndrome. World Neurosurg. Apr 2010; 73(4):411-3. https://www.ncbi.nlm.nih.gov/pubmed/20849802.

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