Prenatal diagnosis of thrombocytopenia-absent-radius (TAR) syndrome
Abstract
The prenatal diagnosis of thrombocytopenia–absent-radius (TAR) syndrome using ultrasound and cordocentesis in the 16th week of gestation is established. The sonographic findings detected in this case included bilateral absence of the radius and club hands with normal thumbs and metacarpals. Because of a high index of suspicion for the syndrome, cordocentesis for fetal blood analysis was performed. Thrombocytopenia, with a platelet count of 14 000/mm3, was identified. The pregnancy was electively terminated and subsequent findings confirmed the sonographic diagnosis. This report, to our knowledge, is one of a very limited number of cases published in the literature, in which the prenatal diagnosis of TAR syndrome was made.
Introduction
Thrombocytopenia–absent-radius (TAR) syndrome is an autosomal recessive blood disorder involving absence of the radius that is usually bilateral, and thrombocytopenia1,2. The thumbs and metacarpals are always present. The ulna and humerus may be absent, and clubfoot deformities may also be present. The affected child has a high mortality rate secondary to hemorrhage early in infancy2. Although this condition is not uniformly fatal, its severe morbidity and high mortality make early prenatal diagnosis of the disease desirable. Prenatal detection of the disease can lead to more appropriate management, including intrauterine platelet transfusion to prevent fetal hemorrhage in labor, a planned of atraumatic delivery, or termination of pregnancy in cases of very early diagnosis. With careful sonographic examination of the long bones, prenatal diagnosis of TAR syndrome can be made theoretically as early as the first trimester, especially in cases of a previously affected child. To our knowledge, however, there have been only a limited number of cases of TAR syndrome detected prenatally3–8. The case presented here is one of the earliest cases of prenatal diagnosis reported.
Case report
A 33-year-old woman, P1-1-0-1, presented at Maharaj Nakorn Chiang Mai Hospital (Thailand) for prenatal care at a gestational age of 16 weeks. Ultrasound examination was requested, owing to large-for-dates uterine size on physical examination. The ultrasound findings showed a single live fetus with bilateral absence of the radius, club hands (1-3), and polyhydramnios with an amniotic fluid index of 20. Fetal biometry, including biparietal diameter and head circumference, was consistent with a menstrual age of 16 weeks. Other findings were unremarkable, and included normal thumbs and metacarpals (Figure 4). TAR syndrome was suspected. Cordocentesis was performed, with consent, for fetal blood analysis of the platelet count. Thrombocytopenia (platelets 14 000 cells/ml3) was identified and the diagnosis of TAR syndrome was established. After counselling, the patient and her husband chose to terminate the pregnancy. Therapeutic abortion was performed with misoprostol, and the subsequent radiograph (Figure 5) and macroscopic findings (male abortus weighing 270 g), confirmed the prenatal diagnosis.

Magnified cross-sectional ultrasound image of the right upper arm and forearm, showing only one long bone (U = ulna) of the forearm. H = humerus.

Longitudinal scan of the right upper extremity, showing absence of the radius and club hand. U = ulna.

Longitudinal scan of the left upper extremity, showing absence of the radius and club hand. U = ulna.

Sonogram of the right hand, showing normal fingers and metacarpals.

Post-abortion radiograph of the right upper arm, showing absence of the radius and normal thumb.
Discussion
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. Congenital heart disease, principally tetralogy of Fallot and septal defects, is present in one-third of the cases1,9. Infant mortality is approximately 40%, usually as a result of hemorrhage early in infancy. Moreover, fetal intracranial hemorrhage has also been reported. Early prenatal diagnosis, as was possible in this case, enabled a termination of pregnancy to be performed before fetal viability. A definitive prenatal diagnosis enables obstetricians to perform intrauterine platelet transfusion to the fetus to prevent fetal hemorrhage in cases in which termination is not an option3–5.
In our case the main sonographic findings which raised the possibility of TAR syndrome were bilateral absence of the radii with normal thumbs and metacarpals. In contrast to several conditions associated with radial ray defects resulting from various factors (Table 1), including chromosomal, teratogenic and genetic causes, in TAR syndrome normal thumbs are typical. However, a fetal platelet count is usually mandatory to establish the diagnosis of TAR syndrome and to differentiate it from other syndromes with malformations of the upper limbs.
Syndromes | Other typical findings |
---|---|
Cornelia de Lange syndrome | Facial defects, growth restriction and mental retardation |
Fanconi syndrome | Absent thumbs, tendency for leukemia |
Holt–Oram syndrome | Upper extremity abnormalities, heart defects |
Nager syndrome | Mandibular hypoplasia, malformed ears |
Roberts syndrome | Severe shortening of limbs, facial anomalies |
TAR syndrome | Thrombocytopenia, thumb always present |
Trisomy 18 | Multiple malformations, clenched hand, craniofacial defects, growth restriction and mental retardation, abnormal hands and feet |
Trisomy 13 | Multiple malformations, holoprosencephaly, facial defects |
VATER associations | Vertebral defects, anal atresia, tracheoesophageal fistula, radial/renal dysplasias |
In contrast to most cases detected with prenatal sonography, the case presented here had no a priori risk of the disorder. In the absence of a familial risk for a radial ray defect, most cases detected prenatally will have more obvious concomitant anomalies, signalling a careful search for an extremity abnormality. In our case, polyhydramnios prompted a search for other malformations.
It appears that routine ultrasonographic assessment of the long bones in addition to measurement of femur length may yield certain diagnoses that would otherwise be missed. The malposition of fetal hands, detectable from 11 weeks of gestation, requires a careful search for longitudinal limb defects of the forearm, especially radial ray defects. The parents may be counselled concerning prenatal management, including the possibility of performing a Cesarean section, intrauterine platelet transfusion or termination of pregnancy in case of early diagnosis.
TAR syndrome is inherited with an autosomal recessive pattern, with a 25% chance of recurrence, although alternative modes of transmission have been shown10. An attempt must therefore be made to exclude this condition in subsequent pregnancies. From our point of view, the sonographic finding of bilateral absence of the radius in the fetus of a woman with a previous child with TAR syndrome enables the diagnosis of the disease to be made confidently with no need for fetal blood analysis by cordocentesis.
We conclude that TAR syndrome can be readily identified prenatally with ultrasound and, if severe thrombocytopenia is confirmed by cordocentesis, therapeutic termination can be offered or platelets transfusion may be considered, especially when the diagnosis is made late in pregnancy.