Thrombocytopenia-Absent Radius Syndrome Clinical Presentation

Episodes of thrombocytopenia begin in the neonatal period in patients with thrombocytopenia-absent radius (TAR) syndrome. ^[17]

About 50% of affected infants are symptomatic in the first week of life, and 90% are symptomatic by the age of 4 months. Thrombocytopenia can fluctuate over time. Therefore, if TAR syndrome is strongly suspected on the basis of one normal platelet count, repeating the blood work is recommended.

Thrombocytopenic episodes are most frequent during the first 2 years of life, when they increase the mortality rate secondary to intracranial hemorrhage. With increasing age, the recurrence of thrombocytopenic episodes decreases. Thrombocytopenia can improve to a near-normal state.

Nonspecific stress, infection, and diet (eg, allergy to cow's milk) may precipitate episodes. Symptoms include purpura, petechiae, epistaxis, melena, hemoptysis, hematuria, hematemesis, and, rarely, intracranial hemorrhage.

Symptomatic cow's-milk allergy is associated with 47% of all cases of TAR syndrome, and patients may present as vomiting, bloody diarrhea, and failure to thrive.

Mental retardation is associated with about 7% of all cases of TAR syndrome. The association of TAR with mental retardation is presumed to be secondary to complications from intracranial hemorrhage precipitated by thrombocytopenia.

Symptoms of acute intracranial hemorrhage in an infant are associated with poor feeding, lethargy, irritability, and fluctuating levels of consciousness.

Structural causes that predispose the patient to mental retardation and other neuropsychiatric disorders (psychosis) have been suggested. ^[18]

Hypoplasia of the cerebellar vermis and corpus callosum has been reported in this syndrome. ^[19]

Upper-extremity abnormalities range from isolated absent radii to phocomelia. Abnormalities include the following:

• Bilateral radial aplasia

• Radial club hand

• Hypoplastic carpals and phalanges

• Hypoplastic ulnae, humeri, and shoulder girdles

• Syndactyly and clinodactyly of fingers and toes

• Selective hypoplasia of middle phalanx, fifth digit

• Altered palmar contours

Greenhalgh and colleagues examined 34 patients with TAR syndrome. ^[15] Their findings demonstrated how the length of the upper limb can affect the patient's functional ability. They divided upper-limb defects into 3 categories of severity, as follows:

• The first group (71%) had mild defects consisting of radial aplasia with various degrees of ulnar and humeral hypoplasia. The patients also had normal shoulder girth and, hence, near-normal upper-body strength, but splints were still useful for periods of prolonged activity of the upper limbs.

• The second group (18%) had increased degrees of limb shortening, humeral hypoplasia, and underdevelopment of the shoulder girth with decreased upper-body strength. Splints were also useful in this group.

• The last group was the most affected, with severe ulnar and humeral shortening and phocomelia.

Lower-extremity anomalies occur in 46% of patients and vary from clinically undetectable changes to phocomelia. These anomalies are usually less severe than those of the upper limbs. Abnormalities include the following:

• Hip dislocation

• Femoral torsion

• Tibial torsion

• Valgus and varus foot deformities

• Deformity of the knee (eg, absence of the patella, patellar dislocation)

• Absent tibiofibular joint

• Abnormal toe placement

• Fifth toe overlapping the fourth

Cardiac anomalies occur in 15-33% of patients and include the following:

• Tetralogy of Fallot

• Atrial septal defect

• Ventricular septal defect (VSD)

Facial anomalies (which occur in 53% of patients) include the following:

• Micrognathia (3-30% of patients)

• Tall, broad forehead

• Facial hemangiomas

• Hypertelorism

• Low, posteriorly rotated ears

Other abnormalities are numerous and include the following:

• Asymmetric first rib

• Cervical rib, cervical spina bifida, fused cervical spine, and nuchal folds

• Meckel diverticulum

• Uterine anomalies

• Dorsal pedal edema

• Hyperhidrosis

• Short stature (95% of patients at or below the 50th percentile)

• Other skeletal malformations

• Renal anomalies (23% of patients), eg, duplex ureter, mild renal pelvis dilatation, horseshoe kidneys

• Intracranial vascular malformation

• Sensorineural hearing loss

• Cleft palate

• Scoliosis

• GI anomalies (eg, esophageal atresia, tracheoesophageal fistula, anal atresia)

• Annular pancreas

Only patients with TAR syndrome consistently have bilateral absence of the radii with the presence of thumbs and 4 digits. In distinguishing TAR from other syndromes involving skeletal abnormalities of the upper extremities, the following features may be of assistance:

• Patients with TAR syndrome always have thumbs, but thumbs are usually absent or hypoplastic in patients with Fanconi anemia and radial defects. Fanconi anemia is also associated with chromosomal fragility, a rare onset of thrombocytopenia before age 1 year, and pancytopenia in children aged 5-10 years. A reliable diagnostic test is a chromosomal breakage study.

• Thumb abnormalities include absent, hypoplastic, and triphalangeal thumbs in Holt-Oram syndrome, and blood counts are normal. The patient often has a family history of heart and limb defects due to the autosomal dominant pattern of inheritance.

• Thrombocytopenia is not often observed in Roberts syndrome (Roberts-SC phocomelia). Most patients with this syndrome have microcephaly and mental retardation.

• Radial hypoplasia is found in patients with Aase syndrome, but the thumb is triphalangeal. Hypoplastic anemia is the usual presentation, similar to that of Blackfan-Diamond syndrome. Thrombocytopenia is not a feature.

Causes of TAR syndrome are not fully elucidated. See Pathophysiology.