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Sneddon Syndrome

Synonyms of Sneddon Syndrome

  • Livedo Reticularis and Cerebrovascular Accidents
  • Sneddon's Syndrome

Disorder Subdivisions

  • No subdivisions found.

General Discussion

Sneddon syndrome is a rare progressive disorder affecting the blood vessels characterized by the association of a skin condition and neurological abnormalities. Characteristics include multiple episodes of reduced blood flow to the brain (cerebral ischemia) and bluish net-like patterns of discoloration on the skin surrounding normal- appearing skin (livedo reticularis). Major symptoms may include headache, dizziness, abnormally high blood pressure (hypertension), heart disease, mini-strokes, and/or stroke. Lesions (infarcts) may develop within the central nervous system as a result of reduced blood flow to the brain and may cause reduced mental capacity, memory loss, and/or other neurological symptoms. The exact cause of Sneddon syndrome is unknown.

Symptoms

Sneddon Syndrome is a slowly progressive disorder of medium-sized arteries, blood vessels that carry blood away from the heart. It is characterized by blockages (occlusions) of the arteries that cause a reduction of blood flow to the brain and to the skin. Associated symptoms vary from case to case.

High blood pressure (hypertension), mini-strokes (transient ischemic attacks), and/or strokes (cerebrovascular accidents) are common. A net-like pattern of bluish skin discoloration surrounding areas of normal-appearing skin (livedo reticularis) is characteristic of this disorder. Painfully cold fingers and toes caused by dilation or constriction of small vessels in response to cold (Raynaud's phenomenon) may also occur. The combination of stroke symptoms and livedo reticularis differentiates this syndrome from other disorders.

Generalized symptoms (e.g., headaches and/or dizziness) may be present for several years before neurological symptoms and/or visible skin discoloration appear. Skin discoloration may precede the development of serious neurological symptoms by several years. In rare cases, neurological symptoms may precede the development of skin discoloration.

Specific neurological symptoms of Sneddon syndrome vary depending upon the location of arterial blockages. These symptoms may include memory loss, impaired vision, muscle weakness, migraine headaches, seizures, confusion, and/or a progressive reduction of mental function. Heart murmurs, heart disease resulting from reduced blood flow to heart tissue (ischemic heart disease), or thickening of the valves between the chambers of the heart (valvular stenosis) have also been diagnosed in people with Sneddon syndrome and may be associated with rheumatic heart disease. In rare cases, impairment of the kidneys may occur in individuals with Sneddon syndrome.

Changes in the sex and ovary-stimulating (gonadotropic) hormones have been reported in women with Sneddon syndrome. These hormonal changes may contribute to obstetrical abnormalities and miscarriage in some women.

Causes

The exact cause of Sneddon syndrome is unknown. Possible immunological, environmental, genetic, and/or other factors are under investigation as potential causes of the disorder.

Sneddon syndrome has been reported in more than one family member (e.g., siblings) in a few cases, supporting the possibility of genetic susceptibility as a factor in some cases. 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. In such cases, genetic predisposition for Sneddon syndrome may be inherited as an autosomal dominant trait.

Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother. In dominant disorders, a single copy of the disease gene (received from either the mother or father) will be expressed "dominating" the other normal gene and resulting in the appearance of the disease. The risk of transmitting the disorder from affected parent to offspring is 50 percent for each pregnancy regardless of the sex of the resulting child.

Symptoms of Sneddon syndrome are caused by a progressive increase in the number of cells in the walls of affected arteries (endothelial proliferation). The cell proliferation leads to a build-up of material, narrowing the arteries and decreasing blood flow. Arteries may become blocked (occluded) and prevent blood from reaching areas of tissue (thrombosis). Clumps of cells may break loose and circulate in the blood stream. The clumps may lodge in an artery and block blood flow (embolism). Tissue loss or damage may occur in areas deprived of blood flow.

Some individuals with Sneddon syndrome have high levels of antiphospholipid antibodies in the blood. Antibodies are part of the body's immune system and act against invading or foreign microorganisms (e.g., bacteria or viruses). Antiphospholipid antibodies mistakenly recognize phospholipids (part of a cell's membrane) as foreign and act against them. There are two main types of antiphospholipid antibodies: anticardiolipin antibody and lupus anticoagulant.

The significance of antiphospholipid antibodies in some cases of Sneddon syndrome is unknown. Some researchers believe that, in familial cases of Sneddon syndrome, affected individuals may have a genetic predisposition to the production of these antibodies.

The presence of antiphospholipid antibodies in some cases of Sneddon syndrome suggests a possible association with antiphospholipid syndrome (see related disorders section below). However, the specific relationship between these two disorders is unknown.

Affected Populations

Sneddon syndrome has been reported more often in females than in males. Symptoms of this rare disorder usually begin in early to middle adulthood, but can occur at any age including childhood. The incidence of Sneddon syndrome has been estimated at four out of every million people per year.

Sneddon syndrome was first identified in the medical literature in 1965. Since that time, significant debate has existed as to whether Sneddon syndrome is a distinct disorder, part of a spectrum of disorders, or a subtype of antiphospholipid syndrome. Some researchers believe that Sneddon syndrome should be separated into primary and secondary cases. Secondary Sneddon syndrome would denote cases that are believed to occur secondary to another disorder or thrombophilic state; primary Sneddon syndrome would denote cases where there was no known cause (idiopathic). Some researchers believe that cases of Sneddon syndrome should be differentiated by whether antiphospholipid antibodies are present.

Related Disorders

Symptoms of the following disorders can be similar to those of Sneddon Syndrome. Comparisons may be useful for a differential diagnosis:

Lupus is a chronic, inflammatory autoimmune disorder affecting the connective tissue. In autoimmune disorders, the body's own immune system attacks healthy cells and tissues causing inflammation and malfunction of various organ systems. In lupus, the organ systems most often involved include the skin, kidneys, blood and joints. Many different symptoms are associated with lupus, and most affected individuals do not experience all of the symptoms. In some cases, lupus may be a mild disorder affecting only a few organ systems. In other cases, it may result in serious complications. Initial symptoms may include excessive fatigue, fever, swollen glands, loss of appetite (anorexia) and weight loss, and headaches. Vascular symptoms in people with Lupus may include a permanent increase in the diameter (dilation) of very small blood vessels (capillary telangiectasis), painfully cold fingers and toes caused by spasms of small blood vessels in response to cold (Raynaud's phenomenon), and inflammation of the blood vessels (vasculitis). There are at least three forms of lupus: the classic form, systemic lupus erythematosus; a form that only affects the skin, discoid lupus erythematosus; and drug-induced lupus erythematosus. The term lupus is most often used to denote systemic lupus erythematosus. (For more information on this disorder, choose "Lupus" as your search term in the Rare Disease Database.)

Polyarteritis nodosa (PAN) is a rare inflammatory systemic disease of the arteries characterized by the presence of granular nodules along the length of small and medium-sized arteries and may be associated with rheumatic heart disease. The initial symptoms may include fever, chills, fatigue, and/or weight loss. People with this disorder may also experience abdominal pain, tingling sensations in the hands and feet (peripheral neuropathy), skin eruptions, joint pain, and/or generalized muscle pain. Polyarteritis nodosa may cause narrowing of the arteries that results in a lack of oxygen to various organs (ischemia), and blood clots. (For more information on this disorder, choose "Polyarteritis Nodosa" as your search term in the Rare Disease Database.)

Antiphospholipid syndrome is a rare blood disorder characterized by recurring blood clots (thrombi) that usually appear before the age of 45 years. Blood clots may cause a stroke or short episodes of low oxygen supply to the brain (transient ischemic attacks or TIA) and the unexplained repeated loss of pregnancies. There may be a family history of blood clotting disorders in some cases. Affected individuals have low levels of platelets in the blood (thrombocytopenia). The exact cause of antiphospholipid syndrome is unknown. (For more information on this disorder, choose "Antiphospholipid Syndrome" as your search term in the Rare Disease Database.)

The following condition may be associated with Sneddon syndrome as secondary characteristics. It is not necessary for a differential diagnosis:

Stroke is one of the most common neurological conditions affecting the central nervous system. Stroke is caused by a blockage of blood flow to part of the brain. This may occur as a result of blockage by a blood clot or the rupture of a weakened area of a blood vessel in the brain (aneurysm). Symptoms may include clumsiness, headaches, speech difficulties, weakness and/or paralysis on one side of the body. The symptoms may progress in stages starting with a feeling of clumsiness an leading eventually to paralysis. All the symptoms may occur within seconds or minutes, striking without warning or pain. A sudden severe headache progressing to a stiff neck, nausea, vomiting, and unconsciousness are symptoms of a stroke due to abnormal bleeding in the brain. Each type of stroke has its own symptoms and progression, depending on the area of the brain that is affected.

Standard Therapies

Diagnosis
The diagnosis of Sneddon syndrome is usually suggested by the combination of neurological symptoms and the pattern of skin discoloration called livedo reticularis. Diagnosis of cerebrovascular damage is confirmed when electronic imaging techniques (e.g., magnetic resonance imaging (MRI), CT scan, cerebral arteriography, HMPAO-SPECT studies) reveal lesions (infarcts) and/or blockages in the brain. Surgical removal and microscopic study of tissue samples (skin biopsy) may confirm the progressive arterial disease (arteriopathy) characteristic of Sneddon syndrome.

Treatment
There is no specific treatment for Sneddon syndrome. Treatment is symptomatic and supportive. Anticoagulants such as aspirin or warfarin may be given to thin the blood and to prevent the formation of blood clots. Vasodilators such as nifedipine may be prescribed to widen (dilate) the blood vessels, reduce blood pressure, and/or reduce the risk of blockage. Immunosuppressive drugs may be used to offset high levels of antiphospholipid antibodies in the blood of some people with Sneddon syndrome.

Genetic counseling may be of benefit for people with Sneddon syndrome and their families.

Investigational Therapies

Research on genetic disorders such as Sneddon Syndrome and their causes is ongoing. The National Institutes of Health (NIH) is sponsoring the Human Genome Project which is aimed at mapping every gene in the human body and learning why they sometimes malfunction. It is hoped that this new knowledge will lead to prevention and treatment of genetic and familial disorders in the future.

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

Sneddon Syndrome Resources

Organizations:

References

TEXTBOOKS
Adams, RD, et al., eds. Principles of Neurology. 6th ed. New York, NY: McGraw-Hill, Companies; 1997:861.

Bennett JC, Plum F., eds. Cecil Textbook of Medicine. 20th ed. Philadelphia, PA: W.B. Saunders Co; 1996:349.

Champion RH, et al., eds. Textbook of Dermatology. 5th ed. Cambridge, MA: Blackwell Scientific Publications; 1992:839-40.

JOURNAL ARTICLES
Tietjen GE, et al. Livedo reticularis and migraine: a marker for stroke risk? Headache. 2002;42:352-55.

Matsumura Y, et al. Sneddon syndrome with multiple cerebral infarctions 12 years after onset of livedo vasculitis: a possible involvement of platelet activation. J Dermatol. 2001;28:508-10.

Wohlrab J, et al. Diagnostic impact and sensitivity of skin biopsies in Sneddon's syndrome. A report of 15 cases. Br J Dermatol. 2001;145:285-88.

Adair JC, et al. Sneddon's syndrome: a cause of cognitive decline in young adults. Neuropsychiatry Neuropsychol Behav Neurol. 2001;14:197-204.

Fetoni V, et al. Clinical and neuroradiological aspects of Sneddon's syndrome and primary antiphospholipid syndrome. A follow-up study. Neurol Sci. 2000;21:157-64.

Heesen M, Rossaint R. Anaesthesiological considerations in patients with Sneddon's syndrome. Paediatr Anaesth. 2000;10:678-80.

Frances C, Piette C. The mystery of Sneddon syndrome: relationship with antiphospholipid syndrome and systemic lupus erythematosus. J Autoimmune. 2000;15:139-43.

Zipper SG, et al. Sneddon syndrome: vasculitis or thrombotic disorder? Med Klin. 2000;95:158-62.

Frances C, et al. Sneddon syndrome with or without antiphospholipid antibodies. A comparative study in 46 patients. Medicine (Baltimore). 1999;78:209-19.

Silva C, et al. Sneddon syndrome. Presentation of 2 cases. Rev Med Chil. 1999;119:1296-300.

Schellong SM, et al. Classification of Sneddon's syndrome. Vasa. 1997;26:215-21.

Pettee AD, et al. Familial Sneddon's syndrome: clinical, hematologic, and radiographic findings in two brothers. Arch Dermatol. 1994;44:399-405.

Charles PD, et al. Sneddon and anitphospholipid antibody syndromes causing bilateral thalamic infarction. Pediatr Neurol. 1994;10:262-63.

Lotz BP, et al. Sneddon's syndrome with anticardiolipin antibodies--complications and treatment. S Afr Med J. 1993;83:663-64.

Zelger B, et al. Sneddon's syndrome. A long-term follow-up of 21 patients. 1993;129:437-47.

Stockhammer G, et al. Sneddon's syndrome: diagnosis by skin biopsy and MRI in 17 patients. Stroke. 1993;24:685-90.

Mayou SC, et al. Hemostatic abnormalities in Sneddon's syndrome. Angiology. 1992;43:342-49.

Sempere AP, et al. Sneddon's syndrome: its clinical characteristics and etiopathogenic factors. Rev Clin Esp. 1992;191:3-7.

FROM THE INTERNET
McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:182410; Last Update:7/24/98.

The information in NORD’s Rare Disease Database is for educational purposes only. It should never be used for diagnostic or treatment purposes. If you have questions regarding a medical condition, always seek the advice of your physician or other qualified health professional. NORD’s reports provide a brief overview of rare diseases. For more specific information, we encourage you to contact your personal physician or the agencies listed as “Resources” on this report.

Report last updated: 2008/05/16 00:00:00 GMT+0

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