Sneddon syndrome primarily affects women in young adulthood. The average age of onset is 30 years old. Some have manifested at 20 years old and others at childhood. It occurs approximately 1 in 250,000 annually.

Approximately half of affected individuals inherit Sneddon syndrome from their parents in an autosomal dominant pattern and approximately half of affected individuals develop Sneddon syndrome sporadically (without a known cause). Others can have Sneddon syndrome secondary to an autoimmune condition, such as, systemic lupus erythematosus, antiphospholipid syndrome, Behcet’s disease, thrombophilia, or mixed connective tissue disease. Sneddon syndrome can be defined as aPL-positive and aPL-negative; where aPL is antiphospholipid, depending if autoimmune disease is present or absence, respectively.

In familial affected individuals, genetic factors may play a role. However, the underlying genetic cause is not currently known. There have been two cases in which loss-of-function mutations in cat eye syndrome at chromosome 22q11.2 and gene CECRI have been reported.

Symptom manifestation is caused by a progressive disease of the small and/or medium arteries. This can lead to reduced blood flow, increased blood pressure, and clotting. Heart disease, valvular disease, and secondary high blood pressure can occur.

The disease may not manifest until it is triggered or activated by certain circumstances, such as a stroke or mini-stroke (transient ischemic attack), intracranial or intraventricular hemorrhage, or livedo racemose. Livedo racemose is a net-like, purple-blue discoloration of the skin. It primarily affects the extremities: the arms, hands, legs, feet, buttocks, and the trunk. It is extremely visible in the cold and can be exacerbated by cold or with pregnancy.

Other affected individuals may have signs of Raynaud syndrome, characterized by episodes lack of blood flow. It causes fingers and/or toes to become white then blue, followed by episodes of blood flow returning, making the area turn red and burn.

Neurological manifestations include strokes, transient ischemic attacks (TIAs), commonly known as mini-strokes, and cerebral infarcts, which is tissue death due to the lack of blood supply caused by a stroke/mini-stroke. Strokes/mini-strokes can cause weakness of only one side of the body, the loss of ability to understand or express speech, and visual defects or vision problems.

Additionally, in Sneddon syndrome, with or without cerebrovascular issues, there is a reduced flow of blood to the brain. This can cause intellectual disability, memory loss, personality changes, and/or other neurological symptoms. This cognitive decline leads to dementia and occurs frequently. Other common cognitive impairments observed are concentration, attention, and visual perception issues.

Rarely, neurological abnormalities and symptoms can occur, such as, spinal stroke, intracranial or subarachnoid hemorrhages (bleeding around or within the brain), seizures, chorea, and myelopathies. Other rare complications are ophthalmic issues and impaired kidney function.

Sneddon syndrome is suspected based on clinical presentations. It is suspected when there are cases of unexplained stroke at a young age, cognitive impairment without a stroke, or livedo racemose is present.

A history of stroke or TIAs evaluation and a cerebral angiography is performed. Cerebral angiography is typically abnormal in most affected individuals.

A skin biopsy is performed to confirm the diagnosis of livedo racemose. The skin biopsy will reveal occlusion of the small arteries under the skin with lack of blood flow to those areas.

An MRI scan is performed to show different brain structure (white matter) changes, infarcts, microbleeds or bleeds, and atrophy (breakdown of tissue). In some affected individuals, there may be a narrowing of arteries and/or vessels in the brain.

Blood tests screen primarily for antiphospholipid antibodies. It is present in more than half of the affected individuals. It also screens for lupus, low white blood cell count, and blood clotting factors.

Other tests include a cardiovascular evaluation, ophthalmic test, and renal function.

There is not established treatment for Sneddon syndrome. Sometimes, long-term anticoagulation with warfarin is prescribed in patients with high INR to prevent cerebrovascular events and issues. High INR means that the blood is thicker, so the risk of clotting is higher. However, optimal management is unknown, and data is limited.

ACE-inhibitors have been suggested to reduce endothelial proliferation, meaning it reduces the growth of endothelial cells in the blood vessels. ACE-inhibitors might help reduce blood pressure and help with ischemia. Prostaglandins have been suggested to improve microvascular perfusion, meaning they could  help with blood flow and gas exchange in the blood vessels to help with ischemia.

When an acute ischemic stroke occurs, the clot is broken (fibrinolysis) with a tissue plasminogen activator (tPA). tPA is a medication that dissolves clots that is given intravenously.

Sneddon syndrome is a chronic, intermittent, or progressive rare disease. It leads to morbidity and dementia in many patients. Neurological symptoms vary depending on the location of the affected blood vessels. Many will experience a reduction and progression of mental and cognitive function decline. There is an estimated 6-year mortality rate of 9.5%.

Avoid smoking and estrogen oral contraceptives to prevent or decrease the severity of neurological symptoms and issues.

http://www.ajnr.org/ajnr-case-collections-diagnosis/sneddon-syndrome

https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=820

https://www.journal-imab-bg.org/statii-08/vol08_1_72-75str.pdf

https://rarediseases.info.nih.gov/diseases/7664/sneddon-syndrome#ref_4980