Thrombocytopenia-absent radius (TAR) syndrome is a rare condition in which thrombocytopenia is associated with bilateral radial aplasia. TAR syndrome was first described in 1951. An autosomal recessive inheritance pattern was proposed because TAR affected more than one member of some families. In 1969, TAR was defined as a syndrome and further classified as the association of hypomegakaryocytic thrombocytopenia and absent radii. The expression varies and includes abnormalities in the GI, skeletal, hematologic, and cardiac systems.  See the images below.
Some have proposed that the association of seemingly disparate skeletal and hematologic abnormalities is related to the simultaneous development of the heart, the radii, and the megakaryocytes at 6-8 weeks' gestation. The similarity of TAR syndrome to congenital rubella suggests intrauterine injury when the involved systems develop, but a common etiologic agent has not been identified.
The exact pathophysiology of the thrombocytopenia is still unclear. The platelet abnormality reflects platelet hypoproduction, for which numerous explanatory theories have been proposed. One suggestion is that a failure in production of humoral or cellular stimulators of megakaryocytopoiesis (eg, thrombopoietin) is responsible for inhibiting platelet production. However, studies by Ballmaier and colleagues and Sekine and associates showed comparable or increased levels of thrombopoietin in patients with TAR compared with healthy control subjects. [2, 3] These findings suggest that the thrombocytopenia is due to a lack of response to thrombopoietin, especially given the observation of normal thrombopoietin receptor expression on megakaryocytes; this raises the question of a defect in c-Mpl signaling.
Many mutations have been postulated, although none had been identified, despite investigations of the c-mpl gene in patients with TAR.  Another proposed candidate gene is a HOX gene. The HOX family of genes plays a major role in embryogenesis and cell differentiation, including differentiation of hematopoietic cell lines. However, Fleischman and colleagues did not detect mutations in the coding sequence of HOX genes known to affect radial development.  Subsequently, an interstitial microdeletion of chromosome 1q was identified in 30 patients with TAR syndrome.  All patients and 75% of unaffected parents in this cohort had the microdeletion, suggesting co-inheritance of an additional modifier gene for disease expression.
Albers and colleagues applied high-throughput sequencing in 5 unrelated patients with TAR and the chromosome 1q21.1 deletion.  They discovered one low frequency single nucleotide polymorphism (SNP) in the noncoding 5' untranslated (UTR) region of the gene RBM8A in 4 of the cases and another low frequency noncoding SNP in the first intron of the same gene. These findings were further confirmed in 48 individuals with TAR. The investigators found coinheritance of the 1q21.1 deletion with either SNP, causing significant decreases in the level of Y14, a protein encoded by RBM8A.  The exact mechanism for which decreased levels of Y14 produces the phenotype associated with TAR syndrome remains to be elucidated. Y14 is part of the exon-junction complex (EJC), a set of proteins associated with transcript export, localization, and splicing, playing a critical in embryonic development. [9, 10] Some studies have suggested defects in signal transduction downstream of thrombopoietin.
TAR syndrome was initially considered an autosomal recessive disease. Some have suggested that the inheritance pattern may be autosomal dominant with variable penetrance.
TAR syndrome rarely occurs in the United States.
The frequency of TAR syndrome is 0.42 case per 100,000 live births in Spain.
The major cause of mortality in TAR syndrome is hemorrhage. The incidence of hemorrhage is limited to the first 14 months of life. In a study by Hedberg and associates, 18 of 20 deaths in 76 patients were due to hemorrhagic events; most of patients who died had platelet counts < 10 X 109/L. 
Bleeding and hemorrhage can also result in clinically significant morbidity, especially intracranial hemorrhage. Hand and upper-extremity function is usually good if radial aplasia is the only skeletal abnormality. However, patients require plastic surgery, occupational therapy, and physiotherapy.
No ethnic or racial predilection is reported.
TAR syndrome is congenital, and patients usually present with symptomatic thrombocytopenia in the first week of life.
The prognosis in TAR is better than in congenital amegakaryocytic thrombocytopenia (CAMT). Survival in TAR plateaus at greater than 70% after age 4 years. The platelet count improves after age 1 year (unlike in CAMT), so platelet transfusion is rarely needed after that.
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