Tar Syndrome Causes, Information, Symptoms, Adsent Radious: TAR syndrome ( T hrombocytopenia – A bsent R adius syndrome, TAR syndrome) is a rare hereditary disease with an autosomal recessive mode of inheritance. The frequency of the disease does not exceed 1 in 100,000 newborns.
The clinical picture is characterized by thrombocytopenia and bilateral absence of radial bones. The absence of radial bones is accompanied by the presence of a thumb, which distinguishes TAR syndrome from other syndromes accompanied by radial anomalies (Holt-Orama syndrome (MIM 142900), Roberts syndrome (MIM268300), and Fanconi anemia (MIM 227650)).
Other skeletal abnormalities associated with TAR syndrome are shortening and, less commonly, aplasia of the ulna and / or humerus bones. The lower limbs are often affected, but, as a rule, to a lesser extent than the upper. Frequent signs are also dislocation of the hip and knee subluxation. Extraskeletal manifestations include cardiac abnormalities, such as Fallot’s tetrad and interatrial septal defects, as well as abnormalities of the urogenital system.
All children with TAR syndrome are born with low platelet count, which leads to hemorrhages in the skin and mucous membranes. The most common are nosebleeds and bleeding in the mouth. Bruises, blood in the feces and hematemesis are frequent symptoms. In rare cases, low platelet count can cause brain hemorrhage. In the first year of life, about 90% of all children with TAR syndrome suffer from minor bleeding in the skin or in the gastrointestinal tract, but sometimes more severe bleeding occurs. In the first year of the child, the number of platelets may periodically increase or decrease, but at the age of 14-15 months the condition of the children usually stabilizes. Platelet count is often normal when a child gets older, although there is a high risk of bleeding.
In most cases, TAR syndrome is caused by a deletion of 200 kb. in the region 1q21.1, exciting the RBM8A gene on one chromosome and rare SNPs in the 5 ‘untranslated region of this gene on another chromosome. In 75% of cases, the deletion is inherited from the parents, in 25% – de novo occurs.
The RBM8A gene is located on the long arm of chromosome 1 in the q21.1 region, consists of 3847 bp. and encodes RNA binding protein 8A (RBM8A, Y14). The RBM8A protein plays an important role during splicing and post-translational modification of mRNA.