Thrombocytopenia-absent radius syndrome (TAR), initially described almost 50 years ago, is a rare congenital disorder of incompletely disclosed etiology that presents with two clinical hallmarks - bilateral agenesis of the radius and thrombocytopenia [1] [2] [3] [4] [5]. Several studies have attempted to delineate the exact mutation responsible for this condition [1] [3] [5], and so far the RBM8A gene located on chromosome 1 seems to be the main location of mutations [2], but solid conclusions are still lacking. The complete absence of radial bones evidently manifests as a markedly shorter length of the forearms, but the bones of the hand are frequently preserved [1] [2] [6]. Still, a variable degree of functional impairment (limited finger extension and marked radial deviation of the hands) is seen in the majority of cases [2] [3]. Conversely, thrombocytopenia, arising from a defective maturation process of megakaryocytes in the bone marrow [3] [4] [5], develops in virtually all patients during the first several months of life, resulting in petechiae and predisposition to gastrointestinal or intracerebral bleeding that may be severe or even life-threatening [1] [2] [3]. In addition to bilateral radial agenesis and thrombocytopenia, other notable features of TAR syndrome include skeletal abnormalities (dysgenesis of axial skeleton, lower limbs and hip dislocation), cow's milk allergy (some authors associate this phenomenon with thrombocytopenia) that may be accompanied by diarrhea, improper development of the genitourinary organs (the female reproductive tract in particular), and congenital heart disease (eg. Tetralogy of Fallot and atrial septal defect) [1] [2] [3].

• Atrial Septal Defect

  Tetralogy of Fallot and atrial septal defect). [symptoma.com]

  septal defects), and cow's milk allergy or intolerance (leading to gastrointestinal disturbance in the first few years of life). [semanticscholar.org]

  Associations cleft lip +/- palate congenital cardiac anomalies in ~30% tetralogy of Fallot atrial septal defect (ASD) dextrocardia jaw under development : micrognathia partial absence of lower limbs fibula aplasia : ~50% 8 Antenatal ultrasound Sonographic [radiopaedia.org]

  septal defect Atrioventricular septal defect Coarctation of aorta Patent ductus arteriosus Tetralogy of Fallot Ventricular septal defect Abnormality of the digestive system Hepatosplenomegaly Meckel diverticulum Pancreatic cysts Abnormality of the eye [ncbi.nlm.nih.gov]

  Cardiac abnormalities eg Atrial septal defect (ASD), ventricular septal defect (VSD), Fallot's tetralogy. [patient.info]

• Primary Amenorrhea

  A 22-year-old woman with TAR syndrome referred to our department with primary amenorrhea. Patient history, physical and laboratory examination, diagnostic laparoscopy, and karyotyping. Physical features in the combination of syndromes presented. [ncbi.nlm.nih.gov]

Because of the rather specific clinical and laboratory findings encountered in thrombocytopenia-absent radius syndrome, a proper physical examination may be sufficient to gain enough evidence about the presence of this ailment. Physicians should completely inspect the patients and observe prominent bilateral forearm shortening with a somewhat preserved anatomy of the hand, and it is not uncommon for the diagnosis to be made prenatally. In fact, fetal ultrasonography can be highly useful for screening the condition prenatally [6]. If thrombocytopenia is identified in the complete blood count (CBC, often being < 50 /109 mm3), or by obtaining a sample through cordocentesis (the preferred method to look at the fetal blood count) solid clinical suspicion could be raised, but it must be pointed out that the platelet count normalize over time [3] [4] [6]. Finally, genetic testing to confirm deletions on chromosome 1 and subsequent RBM8A gene mutations may be indicated as a definite measure to solidify the diagnosis [3]. Some authors classify thrombocytopenia-absent radius syndrome as an autosomal recessive genetic disorder [2] [3], indicating that a family history might provide useful information as well, and thus should be considered as a key component of the diagnostic workup.

When they are present, however, treatment with frequent transfusions and early dialysis may be necessary to prevent serious and life-threatening hemorrhagic episodes. [ncbi.nlm.nih.gov]

Standard Therapies Treatment The treatment of TAR syndrome is directed toward the specific symptoms that are apparent in each individual. [rarediseases.org]

It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. Our staff consists of biologists and biochemists that are not trained to give medical advice . [uniprot.org]

The prognosis is thought to be good if the patient survives to at least one year of age 6 where there is improvement of the thrombocytopenia. [radiopaedia.org]

(Outcomes/Resolutions) The prognosis of Thrombocytopenia-Absent Radius Syndrome is dependent upon the extent and severity of the symptoms: If an affected infant survives the first 2-years successfully, the outcome is generally good The prognosis for upper [dovemed.com]

The prognosis regarding hand and upper extremity function is usually good, providing radial aplasia is the only skeletal abnormality. [patient.info]

The prognosis regarding hand and upper extremity function is usually good, providing radial aplasia is the only skeletal abnormality. 3D ultrasounds may soon become a part of routine care. [degruyter.com]

Prognosis The prognosis in TAR is better than in congenital amegakaryocytic thrombocytopenia (CAMT). Survival in TAR plateaus at greater than 70% after age 4 years. [reference.medscape.com]

Obstetricians & Gynecologists, Family Physicians After completion of this article, the reader should be able to review the rare congenital defects associated with Mullerian agenesis, to determine the genetic etiologies of the associated syndromes with [ncbi.nlm.nih.gov]

Thrombocytopenia-absent radius syndrome (TAR), initially described almost 50 years ago, is a rare congenital disorder of incompletely disclosed etiology that presents with two clinical hallmarks - bilateral agenesis of the radius and thrombocytopenia. [symptoma.com]

Applicable To Congenital thrombocytopenia Hereditary thrombocytopenia Code First Code First Help Certain conditions have both an underlying etiology and multiple body system manifestations due to the underlying etiology. [icd10data.com]

(Etiology) Thrombocytopenia-Absent Radius Syndrome can be caused by inherited or sporadic mutations. In a majority, TAR Syndrome is caused by a mutation or deletion in the RBM8A gene, which localizes to the long arm of chromosome 1. [dovemed.com]

Furthermore, treatment should be focused on the etiology of thrombocytopenia (e.g. discontinuation of the drug that caused the thrombocytopenia, treatment of the underlying infection, chemotherapy, and others). [centogene.com]

Epidemiology [ edit ] The incidence is 0.42 per 100,000 live births. [en.wikipedia.org]

Synonyms: t hrombocytopenia with a bsent r adius (hence TAR) syndrome, tetraphocomelia-thrombocytopenia syndrome Epidemiology This is a rare autosomal recessive condition. [patient.info]

References 1 Martínez-Frías ML, Bermejo Sánchez E, García García A, et al: An epidemiological study of the thrombocytopenia with radial aplasia syndrome (TAR) in Spain. An Esp Pediatr. 49:619–623. 1998. [spandidos-publications.com]

An epidemiological study of the thrombocytopenia with radial aplasia syndrome (TAR) in Spain. An Esp Pediatr. 1998;49:619-623. Sekine I, et al. [rarediseases.org]

Epidemiology Frequency United States TAR syndrome rarely occurs in the United States. International The frequency of TAR syndrome is 0.42 case per 100,000 live births in Spain. [reference.medscape.com]

The exact pathophysiology of the thrombocytopenia is still unclear. The platelet abnormality reflects platelet hypoproduction, for which numerous explanatory theories have been proposed. [reference.medscape.com]

Pathophysiology has been studied recently and Muraoka and Co-workers (79) found that serum thrombopoietin (TPO) level increased significantly higher than normal controls but response of bone marrow progenitors in vitro was defective. [pediatriconcall.com]

In an attempt to understand the genetic basis of the thrombocytopenia associated with TAR syndrome, Ballmaier et al 39 in 1997 investigated the pathophysiology of thrombocytopenia focusing on thrombopoietin (TPO), the main regulator of thrombopoesis, [jmg.bmj.com]

When they are present, however, treatment with frequent transfusions and early dialysis may be necessary to prevent serious and life-threatening hemorrhagic episodes. [ncbi.nlm.nih.gov]

Thrombocytopenia-Absent Radius Syndrome is a genetic condition, and therefore, there are no guidelines or specific methods of preventing the condition from developing. [dovemed.com]

Management options include intrauterine platelet transfusion to prevent fetal hemorrhage in labor; a planned atraumatic delivery (C section) or termination of pregnancy in the second trimester may be contemplated. [radiopaedia.org]

Therapies include intrauterine platelet transfusion to prevent fetal hemorrhage in labor; a planned atraumatic delivery or termination of pregnancy in the second trimester may be contemplated (5). MacDonald MR, Schaefer GB, Olney AH et.al. [fetalultrasound.com]

Prenatal detection of the disease can lead to more appropriate management, including intrauterine platelet transfusion to prevent fetal hemorrhage in labor, as well as a planned atraumatic delivery. [degruyter.com]

1. Greenhalgh K, Howell R, Bottani A, et al. Thrombocytopenia-absent radius syndrome: a clinical genetic study. J Med Genet. 2002;39(12):876-881.
2. Toriello HV. Thrombocytopenia Absent Radius Syndrome. 2009 Dec 8 [Updated 2016 Dec 8]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017.
3. Klopocki E, Schulze H, Strauß G, et al. Complex Inheritance Pattern Resembling Autosomal Recessive Inheritance Involving a Microdeletion in Thrombocytopenia–Absent Radius Syndrome. Am J Hum Genet. 2007;80(2):232-240.
4. Ballmaier M, Schulze H, Strauss G, et al. Thrombopoietin in patients with congenital thrombocytopenia and absent radii: elevated serum levels, normal receptor expression, but defective reactivity to thrombopoietin. Blood. 1997;90(2):612-619.
5. Letestu R, Vitrat N, Massé A, et al. Existence of a differentiation blockage at the stage of a megakaryocyte precursor in the thrombocytopenia and absent radii (TAR) syndrome. Blood. 2000;95(5):1633-1641.
6. Bertoni NC, Pereira DC, Araujo Júnior E, Bussamra LC de S, Aldrighi JM. Thrombocytopenia-absent radius syndrome: prenatal diagnosis of a rare syndrome. Radiol Bras. 2016;49(2):128-129.