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.
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.
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.
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.
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.
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.
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.
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