CLINICAL CHARACTERISTICS:
Thrombocytopenia absent radius (TAR) syndrome is characterized by bilateral absence of the radii with the presence of both thumbs and thrombocytopenia (< 50 platelets/nL) that is generally transient. Thrombocytopenia may be congenital or may develop within the first few weeks to months of life; in general, thrombocytopenic episodes decrease with age. Cow's milk allergy is common and can be associated with exacerbation of thrombocytopenia. Other anomalies of the skeleton (upper and lower limbs, ribs, and vertebrae), heart, and genitourinary system (renal anomalies and agenesis of uterus, cervix, and upper part of the vagina) can occur.

DIAGNOSIS/TESTING:
The diagnosis of TAR syndrome is established in a proband with bilateral absent radii, present thumbs, and thrombocytopenia. Identification of a heterozygous null allele (most often a minimally deleted 200-kb region at chromosome band 1q21.1) intrans with a heterozygous RBM8A hypomorphic allele on molecular genetic testing confirms the diagnosis.

MANAGEMENT:
Treatment of manifestations: Platelet transfusion for thrombocytopenia as needed; central venous catheter as an alternative to repeated venipuncture; orthopedic intervention as needed to maximize function of limbs. Prevention of primary manifestations: Avoidance of cow’s milk to reduce the severity of gastroenteritis and to avoid exacerbations of thrombocytopenia. Prevention of secondary complications: To reduce the risks of alloimmunization and infection, avoid platelet transfusion in older individuals whose platelet counts exceed a particular threshold (10/nL). Surveillance: Platelet count whenever evidence of increased bleeding tendency (bruising, petechiae) occurs.

GENETIC COUNSELING:
TAR syndrome is inherited in an autosomal recessive manner and results from compound heterozygosity of RBM8A pathogenic variants. Affected individuals have one R8BM8A null allele, typically a 200-kb minimally deleted region at chromosome band 1q21.1, and one R8BM8A hypomorphic allele. About 50%-75% of probands have inherited the deletion (null allele) from an unaffected parent; the deletion occurs de novo in about 25%-50% of probands. If both parents carry one variant allele, at conception each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. If only one parent is a carrier of a pathogenic variant (and the other variant/deletion is de novo), each sib of an affected individual has a 50% chance of being an asymptomatic carrier, and a 50% chance of being unaffected and not a carrier. Prenatal diagnosis for pregnancies at increased risk for TAR syndrome is possible using (a) molecular genetic testing if the genetic alterations are identified in the family and/or (b) ultrasound examination to evaluate the limbs.