Thrombocytopenia Absent Radius

Thrombocytopenia with absent radius (TAR) syndrome is a rare inherited condition characterised by, as the name indicates, radial aplasia and significantly reduced platelets (<50 platelets/nL) (1). 

The condition was first described by Shaw and Oliver in 1959, but the name of the syndrome was coined by Hall et al in 1969. (2, 3) Thrombocytopaenia is most severe during infancy and it improves with time to almost normal values in adulthood. (3)

Q87.2 Congenital malformation syndromes predominantly involving limbs

The prevalence of TAR syndrome is estimated at 1:200,000-1:100,000.(1)

The inheritance in TAR syndrome is autosomal recessive. (4) The most prevalent combination is the mutation of the RBM8A gene paired with the 1q21.1 deletion. 

The exact mechanism of the specific signs and symptoms of the syndrome is unknown.
Bone marrow examination reveals decreased megakaryocytes with the preservation of other lineages. (5, 6) 

Cow’s milk allergy is a frequently described symptom and it can be associated with exacerbation of thrombocytopaenia. (1, 7, 8)

The most prominent feature of TAR syndrome is bilateral radial aplasia with radial deviation of the hands (club hands). The ulna and humerus can be absent or dysplastic and lower leg abnormalities can be present as well. (7)

In contrast to the other radial ray defects, the thumbs are present in children affected by TAR syndrome. From other hand abnormalities syndactyly and clinodactyly of the 5th finger have been described. (1) 

The facial features reported in relation to this condition are micrognathia, low set ears and a prominent forehead. (7)

In regards to the involvement of the other systems, renal and cardiac abnormalities (most commonly tetralogy of Fallot and atrial septal defects) were mainly reported. (9) 

There are two approaches to prenatal diagnosis of TAR syndrome. One is molecular genetic testing on the amniotic fluid or chorionic villi sample. The diagnosis is established by identification of a heterozygous null allele on one chromosome (most often a minimally deleted 200-kb region at chromosome band 1q21.1)  with a heterozygous RBM8A hypomorphic allele on the other. (1) The other approach is to perform codocentesis to corroborate the diagnosis in a fetus with bilateral absent radii and present thumbs, by demonstrating thrombocytopenia. (10)

There are different conditions that affect the radial bone and therefore overlap with TAR syndrome:
- Holt-Oram syndrome – skeletal abnormalities of upper limbs and cardiac defects
- Fanconi anaemia – bone marrow failure syndrome
- Roberts syndrome – limb reduction abnormalities, skull and facial abnormalities 
- Okihiro Syndrome (Duane-radial ray syndrome) – radial ray abnormalities and congenital strabismus and abnormal eye movements
- Baller-Gerold syndrome – abnormalities of skull, face and bones of the forearms and hands
- RAPADILINO syndrome - radial and patellar aplasia or hypoplasia are the main features
- VACTERL anomalies - vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities
- Edwards syndrome (Trisomy 18) – radial ray abnormalities, clenched hands, thumb aplasia

There is no official screening for TAR syndrome, however diagnosis can be suspected as early as the dating scan. The main scan finding is an absent radius, and a high level of suspicion can be assumed in the presence of a thumb in contrast to the other radial ray defects. 
There are no other pathognomonic findings, however various associated abnormalities can be present as described above. Therefore, detailed ultrasound scan is indicated.
Serial scans should be performed throughout the pregnancy to monitor for signs of intra-ventricular haemorrhage.

The first year of life is the most critical in TAR syndrome and the mortality is high due to haemorrhagic events. (9) Platelet transfusions reduce this risk. Thrombocytopaenia is most severe during infancy and it improves with time to almost normal values in adulthood. An incerased risk of intellectual disability secondary to intracranial haemorrhage has also been reported. (3) 

The options for antenatal management include intrauterine platelet transfusion or termination of pregnancy can be considered depending on the gestation and the severity of thrombocytopenia. (10, 11)
Joint counselling can be arranged with a paediatric orthopedic surgeon and other specialists in the event of additional structural abnormalities detected on scan. 
As for the mode of delivery, caesarean section is mostly advocated to minimise the risk of trauma and intracranial bleeding. However, a successful vaginal delivery following cordocentesis (to determine if the platelet count was within a safe range) has been described. (12)

Most cases of TAR syndrome are inherited in autosomal recessive manner, although a mutation can occur de novo in one of the genes. 
If both parents are carriers of one gene variant there is a 25% of another affected child, 50% chance of asymptomatic carrier and 25% chance of healthy non-carrier offspring. 
If only one parent is a carrier, and the other gene variant occurred de novo the chance of recurrence is low as it would require another gene mutation to occur spontaneously. However, there is a 50% chance of asymptomatic carrier child. 
Couples with an affected pregnancy or family history of the condition should have genetic counselling, ideally pre-conception. 
In cases of pregnancies achieved through assisted reproductive techniques preimplantation genetic testing can be considered as well as prenatal testing in future pregnancies.

1.    Toriello HV. Thrombocytopenia Absent Radius Syndrome. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Gripp KW, et al., editors. GeneReviews(®). Seattle (WA): University of Washington, Seattle
Copyright © 1993-2022, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.; 1993.
2.    Shaw S, Oliver R. Congenital hypoplastic thrombocytopenia with skeletal deformities in siblings. Blood. 1959;14(4):374-7.
3.    Hall JG, Levin J, Kuhn JP, Ottenheimer EJ, van Berkum KAP, McKusickk VA. Thrombocytopaenia with absent radius (TAR). Medicine. 1969;48(6):411-40.
4.    Klopocki E, Schulze H, Strauss G, Ott CE, Hall J, Trotier F, et al. Complex inheritance pattern resembling autosomal recessive inheritance involving a microdeletion in thrombocytopenia-absent radius syndrome. Am J Hum Genet. 2007;80(2):232-40.
5.    Gounder DS, Pullon HW, Ockelford PA, Nicol RO. Clinical manifestations of the thrombocytopenia and absent radii (TAR) syndrome. Aust N Z J Med. 1989;19(5):479-82.
6.    Halperin D, Pavord S, Myers B. A case series review of patients with Thrombocytopenia and Absent-Radii syndrome (TARS) and their management during pregnancy. Platelets. 2021;32(8):1124-5.
7.    Greenhalgh KL, Howell RT, Bottani A, Ancliff PJ, Brunner HG, Verschuuren-Bemelmans CC, et al. Thrombocytopenia-absent radius syndrome: a clinical genetic study. Journal of Medical Genetics. 2002;39(12):876-81.
8.    Whitfield MF, Barr DG. Cows' milk allergy in the syndrome of thrombocytopenia with absent radius. Archives of Disease in Childhood. 1976;51(5):337-43.
9.    Hedberg VA, Lipton JM. Thrombocytopenia with absent radii. A review of 100 cases. Am J Pediatr Hematol Oncol. 1988;10(1):51-64.
10.    Tongsong T, Sirichotiyakul S, Chanprapaph P. Prenatal diagnosis of thrombocytopenia-absent-radius (TAR) syndrome. Ultrasound in Obstetrics & Gynecology. 2000;15(3):256-8.
11.    Weinblatt M, Petrikovsky B, Bialer M, Kochen J, Harper R. Prenatal evaluation and in utero platelet transfusion for thrombocytopenia absent radii syndrome. Prenat Diagn. 1994;14(9):892-6.
12.    Shelton SD, Paulyson K, Kay HH. Prenatal diagnosis of thrombocytopenia absent radius (TAR) syndrome and vaginal delivery. Prenat Diagn. 1999;19(1):54-7.

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