RUBINSTEIN-TAYBI SYNDROME

Overview

Rubinstein-Taybi syndrome (RTS) is a rare disorder with symptoms such as intellectual disability, postnatal growth retardation, specific facial features, and broad thumbs/big toes. It is mainly caused by pathogenic variants in the CREBBP (50-70%) and EP300 (approximately 5%) genes, which encode transcriptional coactivators involved in cellular processes such as DNA repair and differentiation.

Symptoms

Symptoms include:

• Low intelligence
• Postnatal growth retardation with reduced final height
• Microcephaly
• Distinctive facial features such as a low hairline; broad, arched eyebrows; downward slanting eyelids; columella below the nostrils when seen in profile; retrognathia; and dental anomalies. Broad, often radially angled thumbs
• Broad big toes
• Characteristic facial expression with almost closed eyes when laughing
  
• Seizures are common

Frequency

RTS usually occurs sporadically, and the prevalence is estimated at approximately 1:100,000‑125,000.

Cause

Pathogenic variants in the CREBBP gene, which codes for the cyclic AMP-regulated enhancer binding protein, are a known cause of RTS (approximately 50-70%). In addition, pathogenic variants have been described in the EP300 gene (approximately 5%), which codes for the E1A binding protein p300. These two proteins are transcriptional co-activators involved in many signaling pathways within the cell (e.g., DNA repair, growth, differentiation and apoptosis).

References

Korzus 2017, Adv Exp Med Biol 978:39 / Fergelot et al. 2016, Am J Med Genet A 170: 3069 / Milani et al. 2015, Pediatr 41:4 / Stevens et al. 2014, Gene reviews / Bartsch et al. 2010, Am J Med Genet 152A:181 / Schorry et al. 2008, Am J Med Genet 146A:2512