SNP Shot: Genomic Insights

Thrombocytopenia-absent radius (TAR) syndrome is a condition characterized by two main features: the absence of the radius bone in both forearms and a deficiency in platelets, which are blood cells essential for blood clotting. This platelet deficiency, known as thrombocytopenia, is most pronounced in infancy and often improves with age, sometimes even resolving completely.

Because of the reduced platelet count, individuals with TAR syndrome experience impaired blood clotting, leading to easy bruising and frequent nosebleeds. Severe bleeding episodes (hemorrhages), particularly in the brain and other organs, can be life-threatening, especially during the first year. These hemorrhages can cause brain damage and subsequent intellectual disability. However, affected children who survive the early years without significant brain hemorrhages usually have a normal lifespan and intellectual development.

The severity of skeletal abnormalities varies among individuals with TAR syndrome. The radius, the bone located on the thumb side of the forearm, is almost always absent in both arms. The ulna, the other bone in the forearm, may be underdeveloped or missing in one or both arms. A distinguishing feature of TAR syndrome compared to other similar conditions is the presence of thumbs; individuals with other conditions involving a missing radius usually lack thumbs. However, other hand abnormalities may be present, such as webbed or fused fingers (syndactyly) or curved pinky fingers (fifth finger clinodactyly). Some individuals with TAR syndrome also have skeletal problems affecting the upper arms, legs, or hip sockets.

Other possible features of TAR syndrome include heart or kidney malformations. Some individuals may have distinctive facial features, such as a small lower jaw (micrognathia), a prominent forehead, and low-set ears. Approximately half of affected individuals experience allergic reactions to cow's milk, which can exacerbate the thrombocytopenia associated with TAR syndrome.

Inheritance:

TAR syndrome is an autosomal recessive disorder, meaning that both copies of the responsible gene in each cell must be altered for the condition to manifest. This can happen in two ways: either both copies of the RBM8A gene have mutations, or, more commonly, one copy has a mutation and the other is lost due to a deletion on chromosome 1. Individuals with TAR syndrome typically inherit an RBM8A gene mutation from one parent. In roughly 75% of cases, they inherit a copy of chromosome 1 with a specific 200-kb deletion from the other parent. In the remaining cases, the deletion arises spontaneously during the formation of reproductive cells (eggs or sperm) or during early fetal development. Parents who carry an RBM8A gene mutation or the 200-kb deletion usually do not exhibit any signs or symptoms of TAR syndrome themselves.