Roberts syndrome (RBS) – ESCO2 gene

Roberts syndrome (RBS), also known as tetraphocomelia-cleft palate syndrome or Appelt-Gerken-Lenz syndrome, is a genetic disorder characterized by abnormalities in the extremities and face, slow growth and, in half of the cases, mild to moderate intellectual disability.

Signs and symptoms related to this process may include limb abnormalities such as hypomelia (shortening) or even focomelia in severe cases; abnormal or absent digits; contractures; facial abnormalities, including cleft lip with or without cleft palate, micrognathia, hypertelorism, palpebral fissures tilted down, small nostrils and a pointed nose. Other characteristic signs may include microcephaly; corneal opacities; and encephalocele. In addition, people with Roberts syndrome may have abnormalities of the heart, kidneys and genitals.

This process is due to mutations in the ESCO2 (establishment of sister chromatid cohesion N-acetyltransferase 2) gene, located on the short arm of chromosome 8 (8p21.1), which encodes a protein that plays an important role in the adhesion of sister chromatids until the chromosomes are ready to divide.

At least, thirty ESCO2 gene mutations responsible for the development of Roberts syndrome have been described. These mutations inhibit the synthesis of functional ESCO2 protein due to amino acid changes in the protein or because the mutations give rise to an abnormally short protein. The absence of functional ESCO2 protein hinders the adhesion between sister chromatids around the centromere, which delays cell division. A delayed cell division may be a sign that the cell must be removed, thus leading to the loss of cells in various tissues at the beginning of development.

This disease is inherited with an autosomal recessive pattern, which means that both copies of the gene in each cell must have mutations for the alteration to be expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually do not show signs and symptoms of the disease.

Tests performed in IVAMI: in IVAMI we perform the detection of mutations associated with Roberts syndrome (RBS), by means of the complete PCR amplification of the exons of the ESCO2 gene, and their subsequent sequencing.

Recommended samples: non-coagulated blood obtained with EDTA for separation of blood leucocytes, or a card with a dried blood sample (IVAMI can mail the card to deposit the blood sample).