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Thrombocytopenia-Absent Radius Syndrome

TAR Syndrome

The thrombocytopenia-absent radius syndrome, a rare medical entity, is distinguished by bilateral aplasia of the radius on both arms and thrombocytopenia. Additional anomalies include congenital heart disease, agenesis of the genitourinary system, skeletal abnormalities of the lower limbs and the axial skeleton, as well as cow's milk intolerance. The diagnosis rests on clinical findings, ultrasonography (either prenatal or postnatal), laboratory studies, and genetic testing, although the exact mechanism of the disorder remains to be elucidated.


Presentation

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]
  • 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]
  • The heart problems include holes in the atrial chamber of the heart (atrial septal defect) and tetralogy of Fallot. The name tetralogy of Fallot means there are four different defects of the heart.[encyclopedia.com]
  • Cardiac abnormalities eg Atrial septal defect (ASD), ventricular septal defect (VSD), Fallot's tetralogy.[patient.info]
  • septal defects being the most commonly reported lesions. 1, 4 The genetic basis of TAR syndrome is uncertain.[jmg.bmj.com]
Pathologist
  • Melissa Conrad Stöppler, MD Melissa Conrad Stöppler, MD, is a U.S. board-certified Anatomic Pathologist with subspecialty training in the fields of Experimental and Molecular Pathology. Dr.[rxlist.com]
  • Assay Assay and technical information Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication[invitae.com]
Facial Angiofibroma
  • Multiple facial angiofibromas and collagenomas in patients with multiple endocrine neoplasia type 1. Arch Dermatol 1997; 133: 853–857. 3. Gross H, Groh C, Weippl G.[medicaljournals.se]
Hyperhidrosis
  • Cutaneous lesions reported in association with TAR syndrome include vascular lesions (haemangiomas, naevus flammeus), spotty alopecia, redundant nuchal skin folds and hyperhidrosis (4).[medicaljournals.se]
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]
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]

Workup

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.

Treatment

  • 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]
  • CONCLUSION: Patients with TAR syndrome who receive optimal treatment can expect to return to most activities of daily living with some limitation of wrist extension and ulnar deviation and, of course, with a reduced total active range of digital motion[ncbi.nlm.nih.gov]
  • Because of its location, the presence of this muscle may influence the surgical treatment of these patients. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic IV.[ncbi.nlm.nih.gov]
  • 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 treatment options for Thrombocytopenia Absent Radius Syndrome may include: Transfusion of platelets, to compensate for reduced blood platelets Avoiding physical injury and trauma to minimize bleeding events Avoiding blood-thinning medication Bone[dovemed.com]

Prognosis

  • 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]

Etiology

  • 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]
  • 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.[reference.medscape.com]

Epidemiology

  • 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]
  • Synonyms: t hrombocytopenia with a bsent r adius (hence TAR) syndrome, tetraphocomelia-thrombocytopenia syndrome Epidemiology This is a rare autosomal recessive condition.[patient.info]
  • Epidemiology [ edit ] The incidence is 0.42 per 100,000 live births.[en.wikipedia.org]
  • 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]
  • 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]
Sex distribution
Age distribution

Pathophysiology

  • 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]

Prevention

  • 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]

References

Article

  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.

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Last updated: 2019-07-11 19:57