TAR Syndrome

Overview

Thrombocytopenia with Absent Radius (TAR) syndrome is a rare congenital disorder characterized by two primary features: a significantly reduced platelet count (thrombocytopenia) and the bilateral absence of the radius bone in the forearms. Despite the absence of the radius, individuals with TAR syndrome usually have thumbs, which distinguishes it from other radial ray anomalies. The condition presents early in life, often in the neonatal period, and can lead to serious bleeding complications due to thrombocytopenia. TAR syndrome follows a unique genetic pattern and varies in severity, with some cases showing additional skeletal or systemic abnormalities.

Causes

TAR syndrome is caused by mutations or deletions in the RBM8A gene on chromosome 1q21.1. Most cases involve a compound inheritance pattern, meaning that affected individuals have a combination of two different genetic abnormalities:

• A microdeletion of one copy of the RBM8A gene (typically inherited from one parent).

• A single-nucleotide polymorphism (SNP) or point mutation in the non-deleted copy of the gene (inherited from the other parent).

This results in reduced levels of the Y14 protein encoded by RBM8A, which plays a role in RNA processing and platelet production. TAR syndrome is inherited in an autosomal recessive manner, and both parents are usually asymptomatic carriers.

Symptoms

The clinical features of TAR syndrome typically present at birth or within the first few months of life and include:

• Thrombocytopenia – A low platelet count leading to increased bleeding risk. This is especially dangerous in infancy and can cause:

  • Easy bruising

  • Petechiae (small red or purple spots on the skin)

  • Bleeding from the gums or nose

  • Intracranial hemorrhage (in severe cases)

• Absence of the radius bones – Bilateral absence of the radius in the forearms, often leading to short, curved forearms. Importantly, the thumbs are usually present.

• Skeletal anomalies – These may include short stature, hip dislocations, knee abnormalities, or scoliosis.

• Other possible features:

  • Cardiac defects (e.g., atrial septal defect, ventricular septal defect)

  • Gastrointestinal issues such as cow's milk protein intolerance

  • Renal and genitourinary anomalies

Platelet counts may improve with age, but skeletal abnormalities are permanent without surgical correction.

Diagnosis

Diagnosis of TAR syndrome is based on clinical findings and confirmed with genetic testing. Diagnostic steps include:

• Physical examination – Observation of limb malformations and evidence of bleeding or bruising.

• Complete blood count (CBC) – To detect thrombocytopenia, often with platelet counts below 50,000/μL.

• X-rays – To confirm the absence of the radius bones and evaluate other skeletal abnormalities.

• Genetic testing – Detection of microdeletion at 1q21.1 and RBM8A mutations to confirm the diagnosis.

• Echocardiogram and renal ultrasound – Recommended to assess for possible associated anomalies.

Early and accurate diagnosis is important for planning appropriate management and surveillance strategies.

Treatment

There is no cure for TAR syndrome, but treatment focuses on managing symptoms and preventing complications. A multidisciplinary approach is typically required, involving hematologists, orthopedic surgeons, and pediatricians. Treatment strategies include:

• Platelet transfusions – Used during infancy or during episodes of severe thrombocytopenia to prevent or treat bleeding episodes.

• Avoidance of triggers – Such as cow’s milk, which can worsen gastrointestinal bleeding in affected infants with protein intolerance.

• Orthopedic management – May involve physical therapy, splinting, or corrective surgeries to improve limb function and appearance.

• Monitoring and managing associated anomalies – Including cardiac and renal defects, if present.

• Genetic counseling – Advised for families to understand inheritance patterns and recurrence risks.

As the child grows older, platelet counts typically improve, reducing the frequency and severity of bleeding episodes.

Prognosis

The prognosis of TAR syndrome varies depending on the severity of thrombocytopenia and the presence of associated anomalies. Key points include:

• Early infancy – Carries the highest risk due to potential for life-threatening bleeding, especially intracranial hemorrhages.

• Long-term outlook – Many individuals experience a gradual improvement in platelet levels over time and can lead relatively normal lives with proper management.

• Functional outcomes – With timely orthopedic care and physical therapy, many children achieve good use of their upper limbs.

Overall, with early intervention and ongoing multidisciplinary care, the life expectancy and quality of life of individuals with TAR syndrome can be significantly improved.