Thrombocytopenia-Absent Radius (TAR) Syndrome

Thrombocytopenia-Absent Radius (TAR) syndrome is a rare congenital malformation syndrome. Its two defining features are bilateral absence of the radii and a low platelet count present from birth. The combination is unusual and, once seen, is hard to forget.

The feature that makes TAR an examination favourite is the thumb. In most conditions that destroy the radius, the thumb is also deficient or absent, because the radius and thumb share the same radial (preaxial) developmental column. TAR breaks that rule: the radii are gone but the thumbs remain. A child with bilateral absent radii and two present thumbs has TAR until proven otherwise.

TAR is rare. One case report quotes an approximate frequency of about 0.42 per 100,000 live births, which is a useful order-of-magnitude figure rather than a precise population rate (DOI). The condition was first described by Shaw and Oliver in 1959, with the first major patient series reported by Hall and colleagues in 1969; most later reports have been single cases or small series (DOI).

The natural history has two phases that the orthopaedic surgeon must hold in mind at once:

• Infancy is dominated by the blood. The platelet count is typically at its lowest, and bleeding, including intracranial haemorrhage, is the main cause of early death.
• Later childhood and adulthood are dominated by the skeleton. The platelet count usually improves, but the limb deformities, particularly of the knees, persist and can become the main determinant of quality of life (DOI).

TAR is a disorder of both the megakaryocyte lineage and limb patterning, and the genetics explains why the two travel together.

The genetic basis is unusual. Affected individuals typically carry a microdeletion of chromosome 1q21.1 on one allele and a low-expression (hypomorphic) noncoding variant of the RBM8A gene on the other allele. The microdeletion alone is not sufficient to cause TAR, which is why both hits are needed and why the inheritance behaves in a recessive, compound-heterozygous way (DOI).

RBM8A encodes Y14, a core protein of the exon junction complex, which is involved in messenger RNA maturation. Reduced functional Y14 is thought to disturb the development of megakaryocytes (producing the thrombocytopenia) and of the radial limb structures, although the precise mechanism that spares the thumb is not fully understood (DOI).

The haematology is a hypomegakaryocytic thrombocytopenia: the bone marrow has reduced or immature megakaryocytes, so platelet production is low. Clinically, the count is usually lowest in infancy and tends to recover during childhood. Episodes of worsening thrombocytopenia ("platelet crises") can be precipitated by stress, infection and notably by cow's milk intolerance, which is why a feeding history is part of the haematological assessment (DOI).

There is no single grading scale for TAR itself. In practice, classification means two things: placing TAR correctly within the radial-ray differential, and describing the severity of each affected region.

Both upper limbs are involved symmetrically, so an affected child often uses adaptive grasp and compensatory shoulder and trunk movement. Because the thumbs are present, pinch potential is frequently better than in thumb-losing radial-ray conditions, which influences how aggressively the wrist needs to be repositioned.

The history and examination must cover the blood, the whole child and the limbs, in that order of safety.

Haematology

The single most important investigation is the platelet count, with a full blood count and a clear bleeding history. The thrombocytopenia is hypomegakaryocytic, and counts are typically lowest in infancy. Serial counts matter because the trend (usually improving with age) guides the safe timing of surgery.

Radiographs

Obtain radiographs of both forearms, wrists and hands, and of the knees and any symptomatic joints.

• Forearm: confirm bilateral absent radii, assess ulnar length and bowing, and document carpal and metacarpal anatomy.
• Thumb: confirm the present thumb and assess its bony anatomy and stability.
• Knee: look for the dysplastic features described in TAR, including genu varum, a concave distal femur, a convex medial tibial plateau, patellar abnormalities and signs of ligamentous (including cruciate) deficiency (DOI).

Genetic testing

Molecular confirmation requires detecting both the 1q21.1 deletion and the low-expression RBM8A variant, which historically needed several techniques. Next-generation sequencing can now detect both the copy-number change and the point variant in a single workflow, making confirmation more efficient (DOI). Genetic confirmation supports accurate counselling about recessive inheritance and recurrence risk (DOI).

View larger

TAR is frequently a prenatal diagnosis. The topic's presentation table opens with an "antenatal / newborn" line, the fetal specimen in the clinical image comes from a prenatal molecular-cytogenetics study, and the genetics section rests on family counselling - yet the antenatal pathway itself deserves spelling out, because getting the delivery right is part of protecting the thrombocytopenic newborn.

On second-trimester ultrasound the recognisable pattern is bilateral shortening of the forearms with the hands radially deviated but still present, and importantly the hands (and therefore the thumbs) are not absent - which raises TAR alongside the other radial-ray syndromes. The scan cannot confirm the platelet count or the genetics, so ultrasound findings prompt referral for definitive testing rather than a firm label on imaging alone.

Molecular confirmation before birth uses the same two-hit detection as postnatal diagnosis: a chromosomal microarray or copy-number assay for the 1q21.1 deletion on one allele, plus targeted testing for a low-expression RBM8A variant on the other. Next-generation sequencing can capture both the copy-number change and the noncoding variant in one workflow, which is as useful antenatally as it is postnatally (DOI). Where a previous child is affected and both parental alleles are known, testing can be directed and recurrence risk quoted precisely, because the inheritance is biallelic and recessive (DOI).

The practical payoff is delivery planning. A fetus suspected of having TAR should be delivered where paediatric haematology and neonatal care are available, with platelets on standby, because the newborn may be profoundly thrombocytopenic from the first hours of life and intracranial haemorrhage is the leading early cause of death (DOI). Traumatic instrumental delivery (and, by the same logic, any early invasive procedure) is best avoided until the platelet count and bleeding risk are known.

Management is multidisciplinary and staged. The unifying principle is that the bleeding disorder governs the timing of everything skeletal, and that both the upper and lower limbs need a plan.

The viva scenarios in this topic explicitly ask "what perioperative haematological precautions would you take?", and the management framework repeatedly says to "control the platelets" and provide "platelet support as required" - but the practical answer to how you make a TAR patient safe for surgery deserves to be set out, because it is the difference between a safe and an unsafe plan.

The first principle is timing against the natural history. The thrombocytopenia is hypomegakaryocytic and is at its most dangerous in the first year of life, when severe counts and intracranial haemorrhage account for most of the early mortality; it then tends to improve through childhood so that many older children and adults have a much less severe bleeding tendency (DOI). This is exactly why elective reconstruction is pushed beyond infancy: you are not only waiting for the child to grow, you are waiting for the safest haematological window (DOI).

The second principle is that the bleeding risk must be quantified and corrected around any procedure rather than assumed to have resolved. Even in an adult, the platelet status is confirmed and haematology is involved before major elective surgery; in the reported adult knee arthroplasty this perioperative bleeding assessment was part of a safe outcome (DOI). Platelets are transfused to cover surgery and to treat active bleeding, corrected to a level judged safe for the specific procedure, and antiplatelet drugs (including NSAIDs) are avoided. Triggers that can drop the count acutely - infection and cow's milk intolerance - are looked for and treated, because operating into an unrecognised platelet crisis is unsafe.

Intracranial haemorrhage and cardiac disorders are described as common and important causes of death in TAR, which is why early management is dominated by the blood and the heart rather than the limbs (DOI).

TAR is high-yield because it forces correct sequencing. The visible deformity invites you to talk about wrist reconstruction, but the safe answer always starts with the platelet count. It also tests a clean differential: the thumb tells you whether you are dealing with TAR, Fanconi anaemia, Holt-Oram syndrome or a VACTERL pattern, each of which carries a very different systemic risk.

Counselling families should be honest about the two-phase natural history. In infancy, the message is about bleeding precautions, feeding, and avoiding unnecessary procedures. As the child grows, the message shifts to function: the thumbs are present so pinch is often possible, the hands can be helped with therapy and selected surgery, and the knees will need watching for years.

TAR is rare, so there is no large registry or single international guideline; practice is built from case series, cohort studies and specialist genetic reviews, and is consistent worldwide because the biology is the same everywhere.

The most useful global lesson is sequencing: wherever a child with TAR is treated, safe care means controlling the blood and screening the whole child before elective skeletal surgery, then planning lifelong upper- and lower-limb follow-up.

Related pages: Radial Longitudinal Deficiency is the parent classification for the absent radius and carries the Bayne grading, centralisation and radialisation decisions in full - the crucial point being that TAR sits apart from every other radial ray anomaly because the thumbs are present, which is the single fastest bedside discriminator; Thumb Hypoplasia for the spectrum that is absent here and present in Holt-Oram, Fanconi anaemia and VACTERL, and for the Blauth grading a preserved TAR thumb should be measured against; Congenital Hand Overview for where radial deficiency sits among the limb-formation failures; Ulnar Club Hand for the mirror deformity on the postaxial border; Congenital Knee Dislocation and Congenital Lower Limb Deficiency Overview for the lower-limb involvement present in 47 percent of the Greenhalgh cohort, which is the reason this is an orthopaedic rather than purely a hand topic; Haemophilia for the parallel problem of operating on a child with a bleeding diathesis, including the principle that the haematological plan precedes the surgical one; Skeletal Dysplasias for the wider differential of a short, deformed limb with systemic features; and Syndactyly for the other congenital hand difference most often coexisting with a syndromic diagnosis.