SNP Shot: Genomic Insights

STING-associated vasculopathy with onset in infancy (SAVI) is a condition characterized by widespread inflammation, primarily affecting the skin, blood vessels, and lungs. Normally, inflammation is a protective immune response where the body sends signals and immune cells to fight infection or repair tissue. However, in SAVI, excessive inflammation causes damage to the body's own healthy cells and tissues. SAVI is classified as an autoinflammatory disease because it stems from abnormally heightened inflammation.

Symptoms of SAVI appear within the first few months of life and are mainly related to blood vessel problems (vasculopathy) and tissue damage due to impaired blood supply. Infants develop severe skin lesions, especially on the face, ears, nose, fingers, and toes. These lesions start as rashes and can worsen into ulcers and tissue death (necrosis). These skin issues, exacerbated by cold weather, can lead to complications such as ear scarring, nasal septum perforation, or the need for amputation of fingers or toes. Individuals with SAVI also exhibit livedo reticularis, a purplish skin discoloration resulting from abnormalities in the skin's small blood vessels. They may also experience Raynaud's phenomenon, where fingers and toes turn white or blue in response to cold or stress due to problems in the blood vessels supplying the extremities.

Besides skin problems, individuals with SAVI experience recurring low-grade fevers and swollen lymph nodes. They may also develop interstitial lung disease, a widespread lung condition that can cause pulmonary fibrosis (scarring of the lungs) and breathing difficulties. These respiratory complications can be life-threatening. In rare instances, muscle inflammation (myositis) and joint stiffness can also occur.

Inheritance:

SAVI is inherited in an autosomal dominant manner, meaning that only one copy of the mutated gene is enough to cause the disease. Most cases likely arise from new (de novo) mutations in the responsible gene, occurring during the development of eggs or sperm or in the early stages of embryonic development. These individuals usually have no family history of the condition.