Sneddon syndrome

Title

Other Names:

Sneddon's syndrome; Livedo reticularis and cerebrovascular accidents; Cerebro-vascular lesions and livedo reticularis; Sneddon's syndrome; Livedo reticularis and cerebrovascular accidents; Cerebro-vascular lesions and livedo reticularis; Ehrmann-Sneddon syndrome; Livedo racemosa and cerebrovascular accidents; Livedo racemosa-cerebrovascular accident syndrome; Livedo reticularis-cerebrovascular accident syndrome See More

Categories:

Blood Diseases; Congenital and Genetic Diseases; Nervous System Diseases; Blood Diseases; Congenital and Genetic Diseases; Nervous System Diseases; Skin Diseases See More

Summary 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]

Last updated: 8/29/2018

Symptoms 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]

Last updated: 8/29/2018

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.

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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
Seizures	Seizure	0001250
Tremor	Tremors	0001337
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance		0000006
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

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Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 1/1/2020

Cause 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]

Last updated: 8/29/2018

Inheritance Inheritance

Most cases of Sneddon syndrome are sporadic (not inherited), occurring in people with no family history of the disorder. However, some familial cases with an autosomal dominant inheritance pattern have been reported. In these cases, a genetic susceptibility is likely.^[2] A person who is genetically predisposed to a disorder carries a gene (or genes) for the disease, but it may not be expressed unless it is triggered or “activated” under certain circumstances.^[1]

Last updated: 8/29/2018

Diagnosis 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]

lupus anticoagulant
immunoglobulin IgG and possibly IgM anti-cardiolipinantibodies (types of antiphospholipid antibodies, which may be positive in about 60% of cases)
anti-nuclear (ANA) and anti-double-stranded DNA autoantibodies
thrombocytopenia and leukopenia (low white cell count)
VDRL
cryoglobulins
circulating immune complexes
antithrombin-III
protein C or protein S

Last updated: 8/29/2018

Treatment 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]

Last updated: 8/29/2018

Prognosis Prognosis

Sneddon syndrome is a chronic, progressive disease that leads to major morbidity.^[2] The exact neurological symptoms vary, depending upon the location of arterial blockages.^[1] However, the condition often causes progressive reduction of mental and cognitive function. Dementia ultimately occurs in many patients, resulting in early retirement.^[2] Aphasia, the loss of ability to express or understand speech, is also common.^[1] While we are not aware of statistics regarding the life expectancy of people with Sneddon syndrome, studies have estimated the six year mortality rate to be 9.5%.^[5]

Last updated: 8/29/2018

Statistics Statistics

Sneddon syndrome has an estimated annual incidence of approximately 1/250,000.^[2] It has been reported much more often in females than in males, especially young women under the age of 45.^[1] It does occur occasionally in girls as young as 10 years old.^[3]

Last updated: 8/29/2018

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Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Related Diseases Related Diseases

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnoses include reversible cerebral vasoconstriction syndrome, MELAS syndrome, cerebrovascular dementia (see these terms), migraine, the autoimmune diseases with which SS can be associated, and cerebral angiitis. Visit the Orphanet disease page for more information.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

The Centers for Mendelian Genomics program is working to discover the causes of rare genetic disorders. For more information about applying to the research study, please visit their website.

Organizations 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

National Stroke Association
9707 E Easter Lane
Suite B
Centennial, CO 80112
Telephone: 800-787-6537
Fax: 303-649-1328
E-mail: Info@stroke.org
Website: http://www.stroke.org/

Organizations Providing General Support

American Stroke Association
National Center
7272 Greenville Avenue
Dallas, TX 75231
Telephone: 888-478-7653
Website: http://www.strokeassociation.org/

Do you know of an organization? We want to hear from you.

Learn More 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.

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

Have a question? Contact a GARD Information Specialist.

References References

Berlit P. Sneddon Syndrome. National Organization for Rare Disorders (NORD). 2016; http://rarediseases.org/rare-diseases/sneddon-syndrome/.
Berlit P. Sneddon syndrome. Orphanet. March, 2015; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=820.
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.
Kniffin CL. Sneddon syndrome. OMIM. August 4, 2014; http://www.omim.org/entry/182410.
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. http://www.ncbi.nlm.nih.gov/pubmed/20849802.