TAR Syndrome Health Article

Definition

Thrombocytopenia-absent radius (TAR) syndrome is a rare condition that is apparent at birth. Affected infants are born with incomplete or missing forearms. Typically, the bone on the thumb side of the forearm (radius) is absent, but other bones may be missing or abnormally formed. TAR syndrome also causes life-threatening bleeding episodes due to low levels of platelets in the blood (thrombocytopenia). It is inherited in an autosomal recessive manner.

Description

Dr. S. Shaw first wrote about two siblings (a brother and a sister) with missing forearms and bleeding problems in 1956. Thirteen years later, Dr. Judith Hall gave the name and acronym of TAR syndrome to the disorder. She described three families containing nine individuals. TAR syndrome has also been called the tetraphocomelia-thrombocytopenia syndrome.

The forearm is comprised of two bones. The radius is the long bone on the thumb side of the forearm. The ulna is the long bone on the little finger side. In TAR syndrome, the radius is missing on each forearm. Many times the ulna may also be missing or shorter than normal.

As these bone deficiencies are quite obvious at birth, the forearms will look very short. In fact, the hand looks as if it comes directly from the elbow. In more severe cases, the bone of the upper arm is also missing, with the hand connected to the shoulder. Approximately 50% of the time there are other skeletal abnormalities, particularly in the lower limbs.

Each individual seems to be affected somewhat differently. For instance, some individuals with TAR syndrome might have one arm longer than the other arm; another might have both arms short, and bones missing in the feet; a third person might have all four limbs severely affected. The one constant feature is the absence

of the radius bone. The forearm defects cause the hands to be bent inwards towards the body. However, the four fingers and thumb usually look normal.

The other main feature of the syndrome is thrombocytopenia. Thrombocytopenia means abnormally low levels of platelets in the blood. Platelets are made from cells called megakaryocytes. The megakaryocytes are formed in the red bone marrow, lungs and spleen. In TAR syndrome, the megakaryoctyes are either absent, decreased in number or not formed properly. Therefore, the platelets are not properly made. The exact reason remains unknown.

When injury occurs, platelets are needed so that the blood can clot. The process is called blood coagulation. The platelets help initiate this process by attaching to the injured tissue, and clumping together, almost like a temporary patch. The platelets then release an enzyme called thromboplastin. Thromplastin acts to cleave a particle

called fibrinogen (also in the blood) to fibrin. Fibrin is a hard substance that attaches to the injured area, and forms a meshwork (a blood clot). Along with other clotting factors, this permanently stops the bleeding.

In TAR syndrome, the normal process of making platelets is defective. The effect of this is excessive bleeding and bruising. These individuals have frequent nosebleeds and their skin bruises more easily. The platelet problem makes them more prone to bleeding inside the body, such as in the kidney or lungs. Bleeding can also occur inside the brain (intracranial hemorrhage), and be so severe that these infants die from the internal bleeding.

Genetic profile

There have been numerous instances of siblings, each with TAR syndrome. The parents were not affected. A few families have also been seen where the parents were said to be closely related (i.e. may have shared the same altered gene within the family). For these reasons, TAR syndrome is most likely an autosomal recessive disorder. Autosomal means that both males and females can have the condition. Recessive means that both parents would be carriers of a single copy of the responsible gene. Autosomal recessive disorders occur when a person inherits a particular pair of genes which do not work correctly. The chance that this would happen to children of carrier parents is 25% (1 in 4) for each pregnancy.

It is known that the limbs (arms, legs), the heart and the precursors of the blood system form between the fourth and eighth week of pregnancy. The birth defects seen in TAR syndrome must occur during this crucial period of development. As of 2001, the genetic cause remains unknown.

Demographics

TAR syndrome affects both males and females equally. It most likely occurs in every racial and ethnic group. It is estimated that one in every 250,000 infants are born with TAR syndrome. In all, more than 200 individuals with this disorder have been described in the medical literature.