Thrombocytopenia Absent Radius (TAR) syndrome is a rare, inherited disorder affecting approximately one in every 100,000 to 200,000 newborns worldwide. This congenital condition is characterized by a unique combination of skeletal abnormalities and a blood clotting deficiency. The name describes the two primary features: thrombocytopenia (a significantly low count of blood platelets) and bilateral absence of the radius bones in the forearms.
Defining Features and Underlying Cause
The most visible physical characteristic of TAR syndrome is bilateral radial aplasia, meaning the radius bone is missing in both forearms. This absence causes the forearms to be shortened and the hands to be angled inward, often described as “club hands.” Unlike some other radial defects, the thumbs are always present, though other hand and arm bones may also be affected.
The hematological component is thrombocytopenia, a chronic shortage of platelets responsible for initiating blood clotting. This deficiency is caused by a problem with the production of megakaryocytes, the bone marrow cells that produce platelets. The low platelet count dramatically increases the risk of life-threatening bleeding episodes, especially during infancy.
The underlying cause involves the RBM8A gene on chromosome 1. The condition results from compound heterozygosity, where a person inherits two different genetic changes. One copy of the gene is lost due to a microdeletion on chromosome 1q21.1, and the second copy carries a subtle change, often a single nucleotide polymorphism (SNP), which reduces the gene’s function. This combination results in a low level of the RBM8A protein, disrupting the development of both the skeletal system and megakaryocytes.
Associated Non-Skeletal Health Complications
Many individuals with TAR syndrome experience other health problems beyond the defining skeletal and hematological issues. Approximately one-third have congenital heart defects, most commonly an atrial septal defect (ASD), or a “hole in the heart.” These cardiac abnormalities require careful monitoring and may necessitate intervention shortly after birth.
Renal abnormalities are seen in a smaller number of cases, ranging from minor structural malformations to severe defects affecting kidney function. Some patients also exhibit structural differences in the lower limbs, such as hip dislocation or knee joint abnormalities.
Gastrointestinal issues, specifically a pronounced intolerance to cow’s milk protein, are a frequent complication. This allergy can trigger severe gastroenteritis and may worsen the existing thrombocytopenia. Avoiding cow’s milk is a common strategy to manage digestive symptoms and stabilize platelet levels in susceptible infants.
Diagnosis and Early Identification
Diagnosis can begin before birth through prenatal screening. A detailed ultrasound examination can identify the characteristic skeletal abnormalities, such as the bilateral absence of the radius bones, as early as the first trimester. This early identification allows for multidisciplinary planning for the infant’s care immediately after delivery.
Postnatal diagnosis is confirmed by a physical examination noting the limb abnormalities, followed by a complete blood count. The blood test confirms thrombocytopenia, often showing dangerously low platelet levels in the newborn period. The presence of the thumbs, despite the missing radii, helps distinguish TAR syndrome from other radial defects.
Genetic testing provides definitive confirmation of the diagnosis. Molecular analysis confirms the specific genetic changes: the microdeletion on chromosome 1q21.1 and the single nucleotide polymorphism in the second RBM8A gene copy. This confirmation helps rule out other disorders that present with similar symptoms, such as Fanconi anemia.
Management Strategies and Long-Term Outlook
Management requires a coordinated approach involving hematologists, orthopedic surgeons, and genetic specialists. The most pressing concern in infancy is managing thrombocytopenia to prevent life-threatening hemorrhage, particularly in the brain. Platelet transfusions are the cornerstone of care during the first year of life when platelet counts are lowest and the risk of severe bleeding is highest.
Orthopedic interventions focus on maximizing upper limb function. This involves reconstructive surgery to centralize the hand over the ulna, or the use of adaptive devices and prosthetics. Physical and occupational therapy are continuous requirements to improve range of motion and functional independence.
The long-term outlook is generally positive, provided the individual survives the critical first year or two of life. The platelet count tends to improve significantly with age, often normalizing by the time a child reaches school age, which dramatically reduces the risk of serious bleeding. Children who do not suffer a severe hemorrhage in the brain during infancy typically have normal intellectual development and life expectancy.