This information is provided by the National Institutes of Health (NIH) Genetic and Rare Diseases Information Center (GARD).
Singleton-Merten syndrome is a very rare disease that affect many organs. The main features are tooth abnormalities with gum infection; calcifications in the aorta artery and in certain valves of the heart (i.e., aortic and mitral valves); and progressive thinning and weakening of the bones (osteoporosis), especially in the upper and back portions of the skull. Other findings may include neurologic problems, generalized short stature, muscle weakness; poor muscle tone (hypotonia); progressive wasting of the muscles (muscle atrophy); heart arrhythmia, growth and developmental delay; skin problems such as psoriasis; malformation of the hips and/or feet and limbs or fingers, joint problems, tendon rupture, distinct facial features, and vision problems due to glaucoma. Severe systemic lupus erythematosus can also occur with Singleton-Merten syndrome. Singleton-Merten syndrome is caused by mutations in the IFIH1 gene, and in the DDX58 genes (which causes anatypical form of Singleton-Merten syndrome where there are no teeth problems). Inheritance is autosomal dominant, but it may also occur sporadically (in individuals with no history of the condition in their family).
Commonly, people with type I interferonopathies are treated with high doses of intravenous methylprednisolone, oral prednisone and intravenous immunoglobulins during the acute phases with often only partial control of the flares. There are studies trying to find a more effective treatment.
The genes causing Singeleton-Merten syndrome can activate type I interferon (IFN1) responses. Diseases related to INF1 are known as type I interferonopathies. Type I interferonopathies are a group of rheumatic diseases that are frequently severe and have an early-onset. These diseases include Aicardi-Goutières syndrome, familial chilblain lupus, spondyloenchondrodysplasia, the proteasome associated autoinflammatory syndromes, IFN-stimulated gene 15 (ISG15) deficiency, Singleton-Merten syndrome, STING-associated vasculopathy with onset in infancy (SAVI).
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