Introduction:
In the thrombocytopenia-absent radius (TAR) syndrome, each forearm's radius (a bone) is absent. The lack of blood cells necessary for clotting (platelets) is the character of this condition. Thrombocytopenia, or a lack of platelets, typically first manifests in infancy and gradually gets milder with time; in some cases, platelet counts return to normal.
What Is Thrombocytopenia-Absent Radius Syndrome?
An extremely low platelet count and the lack of the radius bone in the forearm are two features of the rare genetic condition known as TAR syndrome (thrombocytopenia with missing radius).
What Are the Causes of Thrombocytopenia-Absent Radius Syndrome?
TAR Syndrome is a rare genetic disorder characterized by low platelet count and absent or underdeveloped radius bone in the forearm. The exact cause of the disorder is still unknown, but some possible contributing factors include the following:
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Genetic Mutations: TAR Syndrome is caused by mutations in the RBM8A gene, which plays a crucial role in the development and function of blood cells.
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Inheritance: TAR Syndrome is an inherited condition as an autosomal recessive pattern. Both parents must carry the mutated gene to pass it on to their children.
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Environmental Factors: While specific environmental factors that increase the risk of developing TAR Syndrome are unknown, exposure to certain chemicals or toxins during pregnancy may be a potential risk factor.
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Complications During Fetal Development: Some researchers believe that complications during fetal development, such as problems with blood flow or oxygen delivery, also can be a contributory factor that causes TAR Syndrome.
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Other Genetic Factors: In addition to RBM8A gene mutations, other genetic factors may also contribute to the development of TAR Syndrome.
What Are the Signs and Symptoms of Thrombocytopenia-Absent Radius (TAR) Syndrome?
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Limb Anomalies: Upper limb involvement tends to be more severe than lower limb involvement in limb abnormalities.
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Cardiac Anomalies: Cardiac anomalies typically consist of septal defects rather than complicated cardiac malformations (like atrial septal, ventricular septal, and patent foramen ovale).
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Gastrointestinal Involvement: Cow's milk allergy or intolerance and a higher risk of gastroenteritis are gastrointestinal involvements. Sensitivity to cow's milk can cause vomiting, diarrhea, failure to thrive, and poor weight gain, necessitating non-bovine milk formulations. Unrelated to cow's milk intolerance, 30 % of people are more prone to gastroenteritis and dehydration, necessitating intravenous fluids.
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Other Hematologic Features: Congenital abnormalities of the kidney and urinary tract (CAKUT), such as horseshoe kidney, hydronephrosis, and pyelectasis, are the most common genitourinary defects. Agenesis of the uterus, cervix, and upper part of the vagina, also known as Mayer-Rokitansky-Kuster-Hauser syndrome, has occasionally been documented.
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Radius hypoplasia or bilateral absence is usually present in people with TAR syndrome. The thumbs are almost always present and are slightly larger, broader, and flatter than usual. Additionally, the thumbs are flexed against the palm and typically perform only a few functions, such as grasping and pinching.
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The ulnae, humeri, and shoulder girdles may also be hypoplastic or absent in the upper limbs. Fingers may exhibit syndactyly, and clinodactyly of the fifth finger is prevalent.
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Nearly half of TAR syndrome patients have lower limb issues, including hip dislocation, coxa valga, femoral and tibial torsion, genu varum, and patella absence. Tetraphocomelia is the most severe limb involvement.
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Congenital thrombocytopenia and early-life thrombocytopenia are both possible. During the first two years of life, platelet counts are typically low; they later rise but do not reach the lower reference threshold.
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The frequent allergy to cow's milk has been linked to increased thrombocytopenia, either directly through immunoglobulin E (IgE) mediated mechanisms or indirectly through increased gastrointestinal bleeding brought on by the loss of coagulation proteins.
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Some infants experience anemia during the first year of life, which cannot always be attributed to thrombocytopenia-related increased bleeding. Some people get severe anemia and need red blood cell transfusions (especially those with the RBM8A mutation c.-21G>A).
How to Diagnose Thrombocytopenia-Absent Syndrome (TAR)?
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The proband (a person acting as the starting point for a family's genetic investigation) must have suggestive findings, a null heterozygous variant (most commonly a 500-kb or 200-kb deletion including RBM8A at chromosome band 1q21.1) in trans, and a heterozygous RBM8A hypomorphic allele identified through molecular genetic testing to make the diagnosis of TAR syndrome.
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Depending on the phenotype, molecular genetic testing methods can combine gene-targeted testing (single-gene testing, multigene panel) and complete genomic testing (exome sequencing, genome sequencing).
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Clinical assessment for upper and lower extremity anomalies.
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Evaluation of blood cell count for thrombocytopenia and anemia.
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Echocardiography.
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Renal ultrasound exam.
What Is the Management of Thrombocytopenia-Absent Syndrome (TAR)?
Treatment of Manifestations:
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Orthopedic treatment is used to improve limb function when necessary. Platelet transfusions for thrombocytopenia should be avoided in older people whose platelet counts are higher than a specific cut-off (10 platelets/nL) to lower the risk of alloimmunization and infection. Standard therapies for genitourinary and cardiac abnormalities are required. Avoid cow's milk to lessen the severity of gastroenteritis and prevent thrombocytopenia flare-ups. Use a central venous catheter instead of numerous venipunctures.
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Treatments range from platelet transfusions to surgery to "normalize" the appearance of the arm, which is significantly shorter and "clubbed," or to centralize the hand over the ulna to improve hand functionality.
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The use of platelet transfusions, which can even be done in gestation, has helped to reduce the infant death rate. The first and perhaps second years of life is the most important time. Most TAR patients see an improvement in platelet levels as they transition from childhood.
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Observations: When bruising or petechiae are present, there is a higher platelet count. At every appointment, look for gastrointestinal symptoms in kids that could be signs of a cow's milk allergy. Nephrologists use serum electrolytes, blood urea nitrogen, and creatinine to evaluate renal function.
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Agents to Avoid: The child should be checked for gastrointestinal symptoms indicating a cow's milk allergy. According to a nephrologist, serum electrolytes, blood urea nitrogen, and creatinine are used to evaluate renal function.
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Pregnancy Management: Most women get thrombocytopenia during pregnancy. Corticosteroids may be used to treat an immunological component that has been superimposed. However, platelet transfusions may be necessary before surgery or to stop bleeding.
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Genetic Counseling: To help people and families make wise medical and personal decisions, genetic counseling entails educating them on the nature, mode(s) of inheritance, and implications of genetic abnormalities.
Conclusion
The major abnormalities associated with TAR syndrome include thrombocytopenia with absence, or hypoplasia, of megakaryocytes and bilateral absence of the radius (100%). The ulna and humerus may also be absent, and clubfoot deformities may also be present. People with TAR syndrome are at significant risk for anesthesia. The risks of bleeding from changed platelet count and function, vascular and airway access issues and probable congenital heart abnormalities should be considered. Before surgery, all hazards should be thoroughly evaluated.
