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TAR Syndrome
(Thrombocytopenia
with Absent Radius) |
| Classification and external resources |
| Specialty |
medical genetics |
| ICD-10 |
Q87.2 |
| ICD-9-CM |
287.33 |
| OMIM |
274000 |
| DiseasesDB |
29769 |
TAR Syndrome (thrombocytopenia with absent radius) is a rare genetic disorder that is characterized by the absence of the radius bone in the forearm, and a dramatically reduced platelet count. This syndrome may occur as a part of the 1q21.1 deletion syndrome
Contents
- 1 Presentation
- 2 Treatment
- 3 Genetics
- 4 Epidemiology
- 5 History
- 6 References
- 7 External links
Presentation
Symptoms of thrombocytopenia, or a lowered platelet count, leads to bruising and potentially life-threatening hemorrhage.
Other common links between people with TAR seem to include heart problems, kidney problems, knee joint problems, frequently lactose intolerance and often thumb hypoplasia
Treatment
Treatments range from platelet transfusions to surgery aimed at either centralizing the hand over the ulna to improve functionality of the hand or aimed at 'normalizing' the appearance of the arm, which is much shorter and 'clubbed.' There is some controversy surrounding the role of surgery. The infant mortality rate has been curbed by new technology, including platelet transfusions, which can even be performed in utero. The critical period is the first and sometimes second year of life. For most people with TAR, platelet counts improve as they grow out of childhood.
- (from a young woman born with TAR Syndrome)It is highly recommended that parents and significant adults involved with children with TAR become involved with one of many available information/ support groups or online forums as not all information can be published here as quickly as it is discovered. Shriners' Hospitals can be a great starting place. Support groups and informative personal websites can be found by simply searching online.
- Children can be fully involved with peers in everyday activities and can adapt quickly by trying new things to discover their abilities and limits at each age of life. People with TAR grow up to be independent, fully functioning, "car-driving", "gift-wrapping", "married-with-kids-of-their-own" kind of adults, happiest when supported and allowed to adapt while being encouraged and challenged, praised most for being persistent and patient, hard-working or clear thinking/communicating problem-solvers rather than simply "smart". Adaptive devices that prove helpful include dressing sticks, bigger buttons or easy closures on clothing, shoe-horns, curved eating utensils, bidets, water pistols (seriously, as an inconspicuous bidet substitute), elastic exercise bands and "pigtail" elastic shoelaces or slip-on shoes whenever possible, levers instead of knobs on doors, remotes instead of keys for door locks when possible, deep-pocket bed sheets, slide-out cupboard shelves or drawers, kitchen aprons with hot-pads sewn into the chest, and rubber protectors over their cell phones to facilitate easier gripping of an awkward rectangle with curled fingers. Having an awesome sense of humor helps too, as does doing a bit a research of developmental milestones for each year of age and not deviating more than one year on each task if possible.
- Kids born with physical challenges learn about their own limitations as they grow and before they develop any psychological hangups about being different so they just accept their condition as having "always been that way" and are open to discussing it with their peers. They also become aware of adults uneasiness and how a mutual realization of even temporarily extended dependency upon adult caregivers may be stressful both for short and long terms. These kids can to tend to ask questions designed to determine trustworthiness of adults upon whom they rely for assistance and benefit most when parents can keep some shared regular recreational activities in their lives, both for physical fitness and distraction and fun. Water play and flying kites can help, as can soccer as no one but goalies use their hands. It's also recommended to get outdoors for nature walks and time with pets or even large animals like horses.
- It is also suggested that kids with this syndrome be encouraged to meet with, and have opportunities to talk to, others who have grown up with this specific condition, to share notes on ways to adapt and help others cope with the physical requirements, and to encourage them to consider all possibilities when making large life decisions.
Genetics
A 2007 research article identified a region of chromosome 1, 1q21.1, containing 11 genes (including HFE2, LIX1L, PIAS3, ANKRD35, ITGA10, RBM8A, PEX11B, POLR3GL, TXNIP, and GNRR2), that is heterozygously deleted in thirty of thirty patients with TAR.[1] This deletion was also found in 32% of unaffected family members, indicating that the condition requires an additional modifier. In 2012, it was discovered that TAR syndrome is a recessive condition that is caused by the person with TAR syndrome having one allele with an abnormality in the RBM8A gene that reduces, but does not eliminate entirely, the production of the protein Y14 and the other allele with the RBM8A gene either absent (due to the microdeletion identified in 2009) or, less commonly, inoperative due to a different abnormality.[2] The combination of these alleles reduces Y14 levels to a level that appears to result in the abnormalities characteristic of TAR syndrome.[3]
A study published in 2012 identified two separate RBM8A SNP abnormalities resulting in reduced Y14 production that were responsible for all but two of the cases studied, one a 5'UTR SNP with a frequency of 3.05% and the other an intronic SNP with a frequency of 0.42% in 7504 healthy individuals of the Cambridge BioResource. The microdeletion was not found in 5919 controls of the Wellcome Trust Case Control Consortium.[4]
If all TAR cases were inherited, the probability of a sibling of a person with TAR syndrome also having TAR syndrome would be 25%. However, because the RBM8A abnormalities causing TAR syndrome sometimes occur due to a mutation occurring for the first time in the person with TAR syndrome, the actual probability is somewhat lower.[5]
If both parents are carriers, at conception each child has a 25% chance of having TAR syndrome, a 50% chance of being an asymptomatic carrier, and a 25% chance of neither having TAR syndrome nor being a carrier.[6]
The children of a person with TAR syndrome will be carriers of TAR. If a person with TAR syndrome has children with a person who has a RBM8A mutation that causes reduced Y14 production, their offspring have a 50% chance of having TAR syndrome and otherwise will be carriers.[7]
Epidemiology
The incidence is 0.42 per 100,000 live births.
History
TAR was first identified in 1956, and was named almost thirteen years later when severe bruising (along with abnormally short forearms) was present in three families with nine newborns.
References
- ^ Klopocki E, Schulze H, Strauss G et al. (2007). "Complex Inheritance Pattern Resembling Autosomal Recessive Inheritance Involving a Microdeletion in Thrombocytopenia–Absent Radius Syndrome". Am. J. Hum. Genet. 80 (2): 232–40. doi:10.1086/510919. PMC 1785342. PMID 17236129.
- ^ Toriello HV. Thrombocytopenia Absent Radius Syndrome. 2009 Dec 8 [Updated 2012 Jun 28]. In: Pagon RA, Adam MP, Bird TD, et al., editors. GeneReviews™ [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2013. Available from: http://www.ncbi.nlm.nih.gov/books/NBK23758/
- ^ Inheritance of low-frequency regulatory SNPs and a rare null mutation in exon-junction complex subunit RBM8A causes TAR, Cornelis A Albers, Dirk S Paul, Harald Schulze, Kathleen Freson, Jonathan C Stephens, Peter A Smethurst, Jennifer D Jolley, Ana Cvejic, Myrto Kostadima, Paul Bertone, Martijn H Breuning, Najet Debili, Panos Deloukas, Rémi Favier, Janine Fiedler, Catherine M Hobbs, Ni Huang, Matthew E Hurles, Graham Kiddle, Ingrid Krapels, Paquita Nurden, Claudia A L Ruivenkamp, Jennifer G Sambrook, Kenneth Smith, Derek L Stemple, Gabriele Strauss, Chantal Thys, Christel van Geet, Ruth Newbury-Ecob, Willem H Ouwehand, Cedric Ghevaert, Nat Genet. Author manuscript; available in PMC 2012 October 1., Published in final edited form as: Nat Genet. 2012 February 26; 44(4): 435–S2. doi: 10.1038/ng.1083, PMCID: PMC3428915
- ^ Id.
- ^ Toriello HV. Thrombocytopenia Absent Radius Syndrome. 2009 Dec 8 [Updated 2012 Jun 28]. In: Pagon RA, Adam MP, Bird TD, et al., editors. GeneReviews™ [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2013. Available from: http://www.ncbi.nlm.nih.gov/books/NBK23758/
- ^ Id.
- ^ Id.
Further reading
- Goldfarb, Charles A.; Wall, Lindley; Manske, Paul R. "Radial Longitudinal Deficiency: The Incidence of Associated Medical and Musculoskeletal Conditions". The Journal of Hand Surgery 31 (7): 1176–1182. doi:10.1016/j.jhsa.2006.05.012. PMID 16945723.
External links
- Thrombocytopenia Absent Radii research study of Inherited Bone Marrow Failure Syndromes (IBMFS)
- GeneReview/NCBI/NIH/UW entry on Thrombocytopenia Absent Radius Syndrome
- These are the opinions of a young American woman who has TAR syndrome, ulnas and thumbs present (as opposed to absent). She is a 30 something mother of 3 daughters, as well as an artist and photographer in her spare time.
|
Diseases of RBCs and megakaryocytes / MEP (D50–69,74, 280–287)
|
|
Red
blood cells |
| ↑ |
|
|
| ↓ |
| Anemia |
| Nutritional |
- Micro-: Iron-deficiency anemia
- Macro-: Megaloblastic anemia
|
|
Hemolytic
(mostly normo-) |
| Hereditary |
- enzymopathy: G6PD
- glycolysis
- hemoglobinopathy: Thalassemia
- Sickle-cell disease/trait
- HPFH
- membrane: Hereditary spherocytosis
- Minkowski–Chauffard syndrome
- Hereditary elliptocytosis
- Southeast Asian ovalocytosis
- Hereditary stomatocytosis
|
|
| Acquired |
- Drug-induced autoimmune
- Drug-induced nonautoimmune
- Hemolytic disease of the newborn
|
|
|
Aplastic
(mostly normo-) |
- Hereditary: Fanconi anemia
- Diamond–Blackfan anemia
- Acquired: PRCA
- Sideroblastic anemia
- Myelophthisic
|
|
| Blood tests |
- MCV
- Normocytic
- Microcytic
- Macrocytic
- MCHC
|
|
|
| Other |
- Methemoglobinemia
- Sulfhemoglobinemia
- Reticulocytopenia
|
|
|
|
Coagulation/
coagulopathy |
| ↑ |
Hyper-
coagulability |
- primary: Antithrombin III deficiency
- Protein C deficiency/Activated protein C resistance/Protein S deficiency/Factor V Leiden
- Prothrombin G20210A
- Sticky platelet syndrome
- acquired:Thrombocytosis
- DIC
- Congenital afibrinogenemia
- Purpura fulminans
- autoimmune
|
|
|
| ↓ |
Hypo-
coagulability |
| Thrombocytopenia |
- Thrombocytopenic purpura: ITP
- TM
- TTP
- Upshaw Schulman syndrome
- Heparin-induced thrombocytopenia
- May–Hegglin anomaly
|
|
| Platelet function |
- adhesion
- aggregation
- Glanzmann's thrombasthenia
- platelet storage pool deficiency
- Hermansky–Pudlak syndrome
- Gray platelet syndrome
|
|
| Clotting factor |
- Hemophilia
- von Willebrand disease
- Hypoprothrombinemia/II
- XIII
- Dysfibrinogenemia
|
|
|
|
|
|
Index of cells from bone marrow
|
|
| Description |
- Immune system
- Cells
- Physiology
- coagulation
- proteins
- granule contents
- colony-stimulating
- heme and porphyrin
|
|
| Disease |
- Red blood cell
- Monocyte and granulocyte
- Neoplasms and cancer
- Histiocytosis
- Symptoms and signs
- Blood tests
|
|
| Treatment |
- Transfusion
- Drugs
- thrombosis
- bleeding
- other
|
|
|
|
Congenital abnormality syndromes (Q87, 759.7)
|
|
| Craniofacial |
- Acrocephalosyndactylia
- Apert syndrome/Pfeiffer syndrome
- Saethre–Chotzen syndrome
- Carpenter syndrome
- Sakati–Nyhan–Tisdale syndrome
|
|
| other: |
- Möbius syndrome
- Goldenhar syndrome
- Cyclopia
- Baller–Gerold syndrome
|
|
|
| Short stature |
- 1q21.1 deletion syndrome
- Aarskog–Scott syndrome
- Cockayne syndrome
- Cornelia de Lange Syndrome
- Dubowitz syndrome
- Noonan syndrome
- Robinow syndrome
- Silver–Russell syndrome
- Seckel syndrome
- Smith–Lemli–Opitz syndrome
- Turner syndrome
|
|
| Limbs |
- Adducted thumb syndrome
- Holt–Oram syndrome
- Klippel–Trénaunay–Weber syndrome
- Nail–patella syndrome
- Rubinstein–Taybi syndrome
|
|
| Gastrulation/mesoderm: |
- Caudal regression syndrome
- ectromelia
- VACTERL association
|
|
|
| Overgrowth |
- Beckwith–Wiedemann syndrome
- Sotos syndrome
- Weaver syndrome
- Perlman syndrome
|
|
| Laurence–Moon–Bardet–Biedl |
- Bardet–Biedl syndrome
- Laurence–Moon syndrome
|
|
Combined/other,
known locus |
- 2 (Feingold syndrome)
- 3 (Zimmermann–Laband syndrome)
- 4/13 (Fraser syndrome)
- 8 (Branchio-oto-renal syndrome, CHARGE syndrome)
- 12 (Keutel syndrome, Timothy syndrome)
- 15 (Marfan syndrome)
- 19 (Donohue syndrome)
- Multiple
|
|
|
Index of developmental medicine
|
|
| Description |
- Embryology
- Cell lines
- Stem cells
- endoderm
- mesoderm
- ectoderm
|
|
| Disease |
- Due to toxins
- Syndromes
- Chromosomal
- Neonate
- Twins
|
|
|
|
Chromosome abnormalities (Q90–Q99, 758)
|
|
| Autosomal |
| Trisomies |
- Down syndrome
- Edwards syndrome
- Patau syndrome
- Trisomy 9
- Warkany syndrome 2
- Cat eye syndrome/Trisomy 22
- Trisomy 16
|
|
| Monosomies/deletions |
- 1q21.1 deletion syndrome/1q21.1 duplication syndrome/TAR syndrome
- Wolf–Hirschhorn syndrome
- Cri du chat/Chromosome 5q deletion syndrome
- Williams syndrome
- Jacobsen syndrome
- Miller–Dieker syndrome/Smith–Magenis syndrome
- DiGeorge syndrome
- 22q11.2 distal deletion syndrome
- 22q13 deletion syndrome
- genomic imprinting
- Angelman syndrome/Prader–Willi syndrome (15)
- Distal 18q-/Proximal 18q-
|
|
|
| X/Y linked |
| Monosomy |
|
|
Trisomy/tetrasomy,
other karyotypes/mosaics |
- Klinefelter syndrome (47,XXY)
- 48,XXYY
- 48,XXXY
- 49,XXXYY
- 49,XXXXY
- Triple X syndrome (47,XXX)
- 48,XXXX
- 49,XXXXX
|
|
|
| Translocations |
| Leukemia/lymphoma |
| Lymphoid |
- Burkitt's lymphoma t(8 MYC;14 IGH)
- Follicular lymphoma t(14 IGH;18 BCL2)
- Mantle cell lymphoma/Multiple myeloma t(11 CCND1:14 IGH)
- Anaplastic large cell lymphoma t(2 ALK;5 NPM1)
- Acute lymphoblastic leukemia
|
|
| Myeloid |
- Philadelphia chromosome t(9 ABL; 22 BCR)
- Acute myeloblastic leukemia with maturation t(8 RUNX1T1;21 RUNX1)
- Acute promyelocytic leukemia t(15 PML,17 RARA)
- Acute megakaryoblastic leukemia t(1 RBM15;22 MKL1)
|
|
|
| Other |
- Ewing's sarcoma t(11 FLI1; 22 EWS)
- Synovial sarcoma t(x SYT;18 SSX)
- Dermatofibrosarcoma protuberans t(17 COL1A1;22 PDGFB)
- Myxoid liposarcoma t(12 DDIT3; 16 FUS)
- Desmoplastic small round cell tumor t(11 WT1; 22 EWS)
- Alveolar rhabdomyosarcoma t(2 PAX3; 13 FOXO1) t (1 PAX7; 13 FOXO1)
|
|
|
| Other |
- Fragile X syndrome
- Uniparental disomy
- XX male syndrome
- Ring chromosome (13; 14; 15; 20)
|
|
|
Index of developmental medicine
|
|
| Description |
- Embryology
- Cell lines
- Stem cells
- endoderm
- mesoderm
- ectoderm
|
|
| Disease |
- Due to toxins
- Syndromes
- Chromosomal
- Neonate
- Twins
|
|
|
