Thrombocytopenia- absent radius syndrome is an uncommon congenital malformation condition characterized by bilateral absence of the radii with the presence of thumbs, and congenital thrombocytopenia. The syndrome is phenotypically variable. It is inherited in an autosomal recessive pattern caused by a 200kb deletion including or null mutation of RBM8A on one chromosome and a non-coding polymorphism in RBM8A on the other chromosome. The estimated prevalence is between 0.5- 1:100,000 and 1:240, 000 births. It affects both sexes equally. Over 150 cases have been previously reported.
The combination of thrombocytopenia and absent radii was first described by Greenwald and Sherman in 1929, and delineated as a syndrome with a description of cardinal manifestations by Hall et al in 1969 [1,2].
The most common clinical features are:
Thrombocytopenia (100%) - symptomatic in over 90% of the cases within the first four months of life. Platelet counts are usually in the range of 15 - 30x109/L in infancy and improve to almost normal range by adulthood. The thrombocytopenia is thought to be secondary to impaired bone marrow production of platelets, despite normal thrombopoetin production and slightly elevated serum levels.The number of megakaryocytes in the bone marrow is strongly reduced. Platelet aggregation and survival times are reduced but overall platelet function tends to be normal and bleeding occurs secondary to low platelet numbers [3,4].
Purpura, petechiae, epistaxis, gastrointestinal bleeding, hemoptysis and hematuria are the usual symptoms. Intracerebral bleeding may also occur but is rare. Severe thrombocytopenia can be precipitated by stress, infection, gastrointestinal disturbances, pregnancy and surgery.
The risk of bleeding may be more severe than expected from the platelet count. Some clinicians suggest that advanced coagulation tests including thromboelastography and platelet function analysis may be of additional benefit before major surgery. The main cause of mortality is hemorrhage . Upper extremity anomalies (100%): Unilateral or bilateral absence of the radius,hand anomalies (presence of thumbs, limited extension of the fingers, hypoplasia of the carpal and phalangeal bones, ulnar, humeral and shoulder anomalies . Lower limb anomalies (47%- 62%): Hip and patellar dislocation, knee dysplasia or ankylosis, phocomelia ,valgus and varus foot deformities . Cow's milk intolerance: Thrombocytopenia may be precipitated by drinking of cow's milk and relieved by its exclusion from the diet [4,6]. Urogenital anomalies (6-23%): Absent uterus and horseshoe kidney [4,6]. Cardiac anomalies (22-33%): Tetralogy of Fallot, ASD, VSD . Other associated congenital anomalies: Micrognathia, cleft palate, intracranial vascular malformation and facial capillary haemangioma in the glabellar region, epilepsy, scoliosis .
The differential diagnosis of TAR syndrome includes: Fanconi anaemia, Roberts syndrome, Holt-Oram syndrome, thalidomide embryopathy, Cornelia de Lange syndrome, VACTERL association, CHILD syndrome, Trisomy 13 and 18, and Rapadilino syndrome.