What is the appropriate treatment plan for a pediatric patient with Thrombocytopenia-Absent Radius (TAR) syndrome, characterized by thrombocytopenia and limb abnormalities?

TAR Syndrome Management

TAR (Thrombocytopenia-Absent Radius) syndrome requires aggressive platelet transfusion for symptomatic thrombocytopenia during the critical first 14 months of life, with supportive orthopedic management and adaptive devices prioritized over surgical reconstruction for limb abnormalities.

Hematologic Management: The Primary Mortality Risk

Critical Period and Monitoring

• The highest mortality risk occurs within the first 14 months of life due to severe hemorrhagic events affecting the brain, gastrointestinal tract, and other organs 1.
• Thrombocytopenia is typically most severe in the first weeks to months of life, with 95% of patients developing platelet counts <50 × 10⁹/L within the first four months 1.
• Platelet counts generally improve spontaneously by 1-2 years of age, reaching near-normal values 1.

Treatment Algorithm for Thrombocytopenia

Platelet transfusion is the first-line therapy for severe or symptomatic thrombocytopenia 1. The management approach differs fundamentally from immune thrombocytopenia (ITP):

• Do NOT use ITP treatments: TAR syndrome involves hypo-megakaryocytic thrombocytopenia (impaired platelet production), not immune-mediated destruction 1. IVIg, corticosteroids, and anti-D therapy—standard for ITP 2—are ineffective because the mechanism is bone marrow failure, not autoimmune destruction.

• Transfusion thresholds: Implement platelet transfusions for:

  • Any clinically significant bleeding regardless of platelet count 1
  • Prophylactic transfusion may be considered during the high-risk neonatal period when counts are critically low 1
  • Close monitoring is mandatory even when asymptomatic 1

Genetic Confirmation

• TAR syndrome is genetically defined by a 1q21.1 microdeletion (330-1100 kb) that includes the RBM8A gene, combined with a single nucleotide polymorphism in the second RBM8A allele 3, 4.
• Array-CGH or quantitative multiplex PCR confirms diagnosis and enables accurate genetic counseling 3.
• The 1q21.1 deletion is inherited from a healthy parent in 80% of cases, demonstrating incomplete penetrance 3.

Orthopedic and Functional Management

Upper Extremity Approach

Avoid aggressive surgical reconstruction and prosthetic fitting—most patients reject these interventions 5.

• Patients with bilateral radial aplasia but preserved thumbs develop functional compensation by approximating themselves closely to objects to use their own hands 5.
• Simple adaptive devices for feeding, dressing, and toileting are well-tolerated and provide greater independence than prostheses 5.
• Upper extremity prostheses are generally rejected because they interfere with the patient's natural compensatory strategies 5.

Lower Extremity Management

• Lower limb anomalies (including phocomelia) occur in 28% of cases 3.
• Most patients with significant lower extremity involvement either reject orthotic/prosthetic intervention or have deformities that preclude functional ambulation 5.
• Powered wheelchairs or motorized carts provide optimal mobility and independence when lower extremity involvement is significant 5.

Optimal Functional Outcome Strategy

The greatest degree of independence comes from:

1. Simple adaptive devices rather than complex prosthetics 5
2. Powered mobility aids when ambulation is compromised 5
3. Avoiding multiple failed surgical or prosthetic attempts that delay functional adaptation 5

Associated Anomalies Requiring Surveillance

Multisystem Involvement

• Cardiac defects: Require echocardiographic screening 6.
• Renal anomalies: Including vesicoureteral reflux and hydronephrosis have been reported; renal ultrasound is warranted 6.
• Gastrointestinal issues: Including cow's milk protein allergy may complicate management 6.
• Cystic hygroma: Has been reported in affected fetuses 3.

Diagnostic Confirmation and Differential

Clinical Diagnostic Criteria

• Bilateral radial aplasia or hypoplasia with preserved thumbs (critical distinguishing feature) 1, 3.
• Thrombocytopenia with hypo-megakaryocytes on bone marrow examination (though peripheral smear may not always show this) 1.
• Female predominance with female:male ratio approximately 2:1 3.

Key Differential Consideration

TAR syndrome must be distinguished from other inherited thrombocytopenias 7, 8. Unlike ITP, TAR syndrome:

• Presents with congenital limb abnormalities 1, 3
• Shows hypo-megakaryocytic thrombocytopenia (production defect) rather than immune destruction 1
• Does not respond to ITP-directed therapies 1

Genetic Counseling Implications

• When the 1q21.1 deletion occurs de novo (20% of cases), recurrence risk is low 3.
• When inherited from a healthy parent (80% of cases), the parent carries the deletion but lacks the second-hit SNP; genetic counseling must address the complex inheritance pattern 3.
• Prenatal diagnosis via array-CGH is possible when TAR syndrome is suspected based on ultrasound findings of bilateral radial aplasia 3.

Critical Pitfalls to Avoid

• Never assume this is ITP: The presence of limb abnormalities immediately excludes primary ITP and mandates consideration of inherited thrombocytopenia syndromes 7, 8.
• Never delay platelet transfusion: Waiting for spontaneous improvement during the critical first 14 months risks fatal hemorrhage 1.
• Never pursue aggressive upper extremity surgical reconstruction: This typically fails and delays functional adaptation 5.
• Never overlook associated anomalies: Cardiac, renal, and GI screening prevents missed life-threatening complications 6.