Thrombocytopenia With Absent Radii Syndrome Research Articles

Thrombocytopenia with absent radii (TAR) Syndrome in a male child: report of a rare case

Introduction: Thrombocytopenia with absent radii (TAR) Syndrome is a rare congenital defect presents with hypomegakaryocytic thrombocytopenia and bilateral radial aplasia and preserved thumb.Case presentation: A three and half year’s old male baby born out of non-consanguineous marriage with thrombocytopenia and bilateral absence of radius. Such type of anomaly has been previously reported in the children of a non- consanguineous marriage was few.Conclusions: Though rare incidence, all thrombocytopenia with any skeletal deformity cases in newborn or infancy to toddler age group must be thoroughly investigated to exclude TAR syndrome. Case is presenting here because of rarity.International Journal of Human and Health Sciences Vol. 02 No. 02 April’18. Page : 91-93

Acute myeloid leukemia in a patient with thrombocytopenia with absent radii: A case report and review of the literature

Thrombocytopenia with absent radii (TAR) syndrome is a rare congenital disorder characterized by low platelet counts of various severity, bilateral absent radii but thumbs are usually present. TAR syndrome is not generally associated with bone marrow failure or malignancy. Janus kinase-2, myeloproliferative leukemia protein, and calreticulin are not mutated in TAR patients. Only four cases of leukemia were reported in TAR patients in the literature: three acute myeloid leukemia (AML) and one acute lymphoblastic leukemia. Of the three cases of AML found in TAR patient, only one was reported in an adult. We report a case of myelodysplastic syndrome progressing to AML with calreticulin driver mutation in an adult male with TAR syndrome who was successfully treated with hematopoietic allogeneic stem cell transplantation.

TAR syndrome and esophagial atresia: a concomitant or variant condition?

Thrombocytopenia with absent radii (TAR) is rare cause of neonatal thrombocytopenia. TAR syndrome and esophageal atresia with tracheoesophageal fistula has been reported in only two cases in literature. Our case was the first in literature with unilateral TAR syndrome and bilateral absence of thumbs accompanying EA.

Acute myelogenous leukemia in an adult with thrombocytopenia with absent radii syndrome

Acute myelogenous leukemia with t(8;21)(q22;q22) developed in a 42-yr-old woman having thrombocytopenia with absent radii syndrome (TARS). Standard induction and postremission therapies were safely administered. With each successive chemotherapy, the onset of platelet recovery was not delayed, but peak platelet counts were persistently suppressed. Nine months after achieving complete hematologic and cytogenetic remission, she remains severely thrombocytopenic (platelet count 6-12 x 109/L). She is, however, asymptomatic and transfusion independent. Of interest is the transient normalization of platelet count (rebound relative thrombocytosis). Our report and review of the literature suggests that TARS, contrary to previous belief, may be associated with increased risk of acute leukemia.

Amegakaryocytic thrombocytopenia and radio-ulnar synostosis are associated with HOXA11 mutation.

The association of bone marrow failure and skeletal defects has been frequently noted, but the genetic basis for most of these syndromes remains unclear1. We have identified an unusual association of amegakaryocytic thrombocytopenia and radio-ulnar synostosis in two unrelated and nonconsanguinous families that are of different ethnic backgrounds (Fig. 1a). The fathers and all affected children in both families have the same skeletal defect, proximal fusion of the radius and ulna (Fig. 1b), resulting in extremely limited pronation and supination of the forearm. Three children also had symptomatic thrombocytopenia, with bruising and bleeding problems since birth, necessitating correction by bone marrow or umbilical-cord stem-cell transplantation. The fathers had normal platelet counts and no history of bleeding or bruising. This set of clinical findings appears distinct from any other syndromes of bone marrow failure and skeletal malformations, including thrombocytopenia with absent radii (TAR) syndrome and Fanconi anaemia1, 2, 3. So far, proximal radial-ulnar synostosis has not been associated with the TAR syndrome, which, as its name implies, typically has a more pronounced radial defect. The absence of excessive diepoxybutane-induced chromosomal breakage before stem cell transplantation from our patients is not consistent with Fanconi anaemia.

Defective c-Mpl signaling in the syndrome of thrombocytopenia with absent radii.

Thrombocytopenia with absent radii (TAR) syndrome is a rare congenital defect with severe hypomegakaryocytic thrombocytopenia and bilateral radial aplasia. To elucidate a possible relationship between thrombocytopenia in TAR and defects in the thrombopoietin (TPO)/c-Mpl system, we examined TPO activity in sera from six patients and in vitro reactivity of the patients' platelets to recombinant human TPO. We found elevated TPO serum levels in all patients, excluding a TPO production defect as a pathomechanism for the thrombocytopenia. In contrast to healthy controls, however, platelets of TAR patients failed to respond to recombinant TPO as measured by testing TPO synergism to suboptimal concentration of platelet activators. Most interestingly, TPO-induced tyrosine phosphorylation of platelet proteins was completely absent (four out of five) or markedly decreased (one out of five). More detailed investigations of the signal cascades of c-Mpl demonstrated the absence of Jak2 phosphorylation after TPO stimulation in a TAR patient's platelets. A defect in the early events of c-Mpl signal transduction might be the reason for impaired megakaryocytopoiesis in TAR syndrome.

Thrombopoietin in Patients With Congenital Thrombocytopenia and Absent Radii: Elevated Serum Levels, Normal Receptor Expression, But Defective Reactivity to Thrombopoietin

AbstractThe pathophysiology of thrombocytopenia in the syndrome of thrombocytopenia with absent radii (TAR) is not yet understood. We examined thrombopoietin (TPO) serum levels and the in vitro reactivity of platelets to TPO in five patients affected with TAR syndrome. We found elevated TPO serum levels in all patients tested, excluding a TPO production defect as cause for thrombocytopenia in TAR syndrome. In addition, we found similar expression of the TPO receptor c-Mpl on the surface of platelets from TAR patients (5 of 5) and a similar molecular weight of the receptor as compared with healthy controls (4 of 4). Platelet response to adenosine diphosphate or thrombin receptor agonist peptide SFLLRN (TRAP) was normal in TAR patients. However, in contrast to results with healthy controls we could show absence of in vitro reactivity of platelets from TAR patients to recombinant TPO as measured by testing TPO synergism to adenine diphosphate and TRAP in platelet activation. TPO induced tyrosine phosphorylation of platelet proteins was completely absent (3 of 4) or markedly decreased (1 of 4). Our results indicate that defective megakaryocytopoiesis/thrombocytopoiesis in TAR syndrome is not caused by a defect in TPO production but a lack of response to TPO in the signal transduction pathway of c-Mpl.

Thrombopoietin in Patients With Congenital Thrombocytopenia and Absent Radii: Elevated Serum Levels, Normal Receptor Expression, But Defective Reactivity to Thrombopoietin

The pathophysiology of thrombocytopenia in the syndrome of thrombocytopenia with absent radii (TAR) is not yet understood. We examined thrombopoietin (TPO) serum levels and the in vitro reactivity of platelets to TPO in five patients affected with TAR syndrome. We found elevated TPO serum levels in all patients tested, excluding a TPO production defect as cause for thrombocytopenia in TAR syndrome. In addition, we found similar expression of the TPO receptor c-Mpl on the surface of platelets from TAR patients (5 of 5) and a similar molecular weight of the receptor as compared with healthy controls (4 of 4). Platelet response to adenosine diphosphate or thrombin receptor agonist peptide SFLLRN (TRAP) was normal in TAR patients. However, in contrast to results with healthy controls we could show absence of in vitro reactivity of platelets from TAR patients to recombinant TPO as measured by testing TPO synergism to adenine diphosphate and TRAP in platelet activation. TPO induced tyrosine phosphorylation of platelet proteins was completely absent (3 of 4) or markedly decreased (1 of 4). Our results indicate that defective megakaryocytopoiesis/thrombocytopoiesis in TAR syndrome is not caused by a defect in TPO production but a lack of response to TPO in the signal transduction pathway of c-Mpl.

Thrombocytopenia with absent radii. A review of 100 cases.

The syndrome of thrombocytopenia with absent radii (TAR) is a rare congenital syndrome in which the characteristic hematological findings are hypomegakaryocytic thrombocytopenia, periodic leukemoid reactions, and eosinophilia. The thrombocytopenia usually presents at birth or during the neonatal period and may be profound, accounting for significant morbidity. However, resolution of the thrombocytopenia usually occurs after the first year. In this review of 100 cases, the clinical manifestations, pathophysiology, genetics, and treatment are discussed in detail. With the increased understanding of the natural history and pathophysiology of the hypomegakaryocytic thrombocytopenia in the TAR syndrome, in conjunction with the advances in supportive therapy discussed, the outlook for patients with this syndrome has become quite good.

Micrognathia—prenatal ultrasonographic diagnosis

The first case of prenatal real-time ultrasonographic diagnosis of micrognathia is presented. Diagnosis was made at 17 weeks' gestation in the fetus of a patient with previous infant affected with the syndrome of thrombocytopenia with absent radii (TAR). Recognition of micrognathia as a part of TAR syndrome and the easy visualization of fetal facial bones in the second trimester made diagnosis possible.