Expanding the phenotype of thrombocytopenia absent radius syndrome with hypospadias

J Biotechnol. 2020 Mar 10:311:44-48. doi: 10.1016/j.jbiotec.2020.02.011. Epub 2020 Feb 25.


Rare genetic diseases and syndromes may appear with unique features in some patients. In genetically-solved cases, this situation indicates a phenotypic expansion of the syndrome with additional features (i.e. the disease-associated gene gives rise to unusual clinical presentation). However, this situation can also hide a multilocus pathogenic variation that cannot be solved genetically except by a massive sequencing approach, such as exome sequencing. Here we describe the case of a child with bilateral radial aplasia, transient thrombocytopenia and anemia, cow's milk intolerance, hypospadias, facial dysmorphism, mild hypothyroidism and umbilical and inguinal hernia. Bilaterally absent radius, presence of thumbs and low platelet count are pathognomonic of thrombocytopenia absent radius (TAR) syndrome, but the child also showed other features beyond those reported in the literature. Since various diseases resembling the proband's phenotype required differential diagnosis, clinical exome sequencing was performed. The results showed compound heterozygous mutations in the RBM8A gene, confirming the suspicion of TAR syndrome. A truncating heterozygous variant in the DUOX2 gene, known to be associated with transient thyroid dyshormonogenesis type 6 (TDH6), was also detected and may explain the proband's mild hypothyroidism.

Keywords: Exome sequencing; TAR syndrome; Thrombocytopenia absent radius syndrome; Thyroid dyshormonogenesis type 6.

Publication types

  • Case Reports

MeSH terms

  • Congenital Bone Marrow Failure Syndromes / genetics*
  • Congenital Hypothyroidism / genetics
  • Genetic Testing
  • Humans
  • Infant
  • Male
  • Mutation / genetics
  • Phenotype
  • RNA-Binding Proteins / genetics
  • Radius
  • Thrombocytopenia / genetics*
  • Upper Extremity Deformities, Congenital / genetics*


  • RBM8A protein, human
  • RNA-Binding Proteins

Supplementary concepts

  • Absent radii and thrombocytopenia
  • Thyroid Dyshormonogenesis 6