Thrombocytopenia-Absent Radius (TAR) Syndrome is a rare genetic disorder characterized by a distinct combination of physical and hematological issues present from birth. The condition affects the body’s ability to form blood clots and results in a specific skeletal malformation. This combination of symptoms makes TAR syndrome a complex condition that requires specialized, lifelong medical attention.
The Defining Characteristics
The condition’s name points directly to its two prominent features: thrombocytopenia and absent radii. Thrombocytopenia is a low count of platelets, small blood cells crucial for clotting. While a normal platelet count ranges from 150 to 400 platelets per nanoliter (nL), counts in TAR syndrome are often below 50 platelets/nL, especially in infancy. Low platelet numbers increase the risk of hemorrhage, or severe bleeding, which is the most life-threatening aspect of the syndrome during the first two years of life.
The skeletal abnormality is the bilateral absence of the radius bone, the bone on the thumb side of the forearm. This missing or severely underdeveloped bone causes the forearms to be significantly shortened and leads to the hands being positioned at an angle, known as radial club hand. A key feature that helps distinguish TAR syndrome from other radial ray deficiencies is the presence of the thumbs, which are nearly always present, though they may have limited function. The structural issues in the forearms and hands can severely limit mobility and the ability to grasp objects.
Genetic Origin and Inheritance
TAR syndrome is caused by genetic changes involving the RBM8A gene, which provides instructions for making a protein involved in cellular protein production. The underlying genetic mechanism requires specific alterations on both copies of chromosome 1.
An individual typically inherits a microdeletion on chromosome 1q21.1, known as a null allele, from one parent. They must also inherit a low-frequency, non-coding single nucleotide variant (SNV) of the RBM8A gene, known as a hypomorphic allele, from the other parent. This combination results in a significantly reduced amount of the RBM8A protein, causing the syndrome. This inheritance pattern is described as compound heterozygosity, a variation of autosomal recessive inheritance. In 25% to 50% of cases, the microdeletion occurs spontaneously in the affected individual rather than being inherited from a parent.
Comprehensive Clinical Manifestations
TAR syndrome is a multi-system disorder that involves significant health issues beyond the defining features. Skeletal anomalies frequently extend beyond the forearms, affecting the upper and lower limbs. Other upper limb issues can include an underdeveloped or absent ulna, or issues with the humerus and shoulder girdle.
In the lower body, nearly half of affected individuals experience problems such as hip dislocation, genu varum (bow-legs), and issues with the patella or knees. The severity of these additional skeletal manifestations varies widely among individuals. Beyond the bones, about half of people with TAR syndrome have an allergic reaction to cow’s milk protein, which can trigger or worsen episodes of thrombocytopenia.
Congenital anomalies affecting major organs are also a concern. Cardiac defects such as Tetralogy of Fallot or other structural heart malformations are common. Kidney (renal) abnormalities are also common, sometimes involving structural issues or functional problems. The severity of the thrombocytopenia is the strongest predictor of prognosis in early life, given the risk of life-threatening bleeding, especially into the brain.
Treatment and Long-Term Management
The management of TAR syndrome requires a multidisciplinary approach focused on minimizing bleeding risks and maximizing limb function. The most immediate concern in infants is the hematological management of the low platelet count. Platelet transfusions are the cornerstone of treatment during “platelet crises” or when a patient is at high risk of hemorrhage, such as before surgery.
Physicians aim to maintain a platelet count above 40 platelets/nL during critical periods to prevent major vascular bleeding. Precautions are taken to avoid trauma, especially to the head, and antiplatelet medications like aspirin must be avoided. Since cow’s milk allergy can exacerbate the low platelet count, infants are often placed on a milk-free diet, which can help alleviate symptoms.
Orthopedic Care
Orthopedic management focuses on improving the function of the hands and forearms. Non-surgical options include physical and occupational therapy to encourage mobility and independence, often utilizing adaptive devices. Surgical interventions, such as centralization of the hand over the ulna, may be performed to improve the range of motion and overall function of the limb.
Long-term care involves continuous monitoring by a team of specialists, including hematologists, orthopedic surgeons, cardiologists, and nephrologists. The severity of thrombocytopenia often decreases dramatically after the first two years of life, with platelet counts frequently rising to near-normal levels by school age. Individuals who avoid severe internal bleeding typically have a normal life expectancy and normal intellectual development, though they will continue to manage the skeletal limitations.