Rubinstein-Taybi syndrome is a condition characterized by short stature, moderate to severe intellectual disability, distinctive facial features, and broad thumbs and first toes. Additional features of the disorder can include eye abnormalities, heart and kidney defects, dental problems, and obesity. These signs and symptoms vary among affected individuals. People with this condition have an increased risk of developing particular types of noncancerous brain and skin tumors.
Rubinstein-Taybi syndrome is uncommon; it occurs in an estimated 1 in 100,000 to 125,000 newborns.
Mutations in the CREBBP gene cause about half of cases of Rubinstein-Taybi syndrome. The CREBBP gene provides instructions for making a protein that helps control the activity of many other genes. This protein, called CREB binding protein, plays an important role in regulating cell growth and division and is essential for normal development before birth. Because one copy of the CREBBP gene is deleted or mutated in people with Rubinstein-Taybi syndrome, their cells make only half of the normal amount of CREB binding protein. A reduction in the amount of this protein disrupts normal development before and after birth. Abnormal brain development is thought to underlie intellectual disability in people with Rubinstein-Taybi syndrome. Researchers have not determined how CREBBP gene mutations lead to other signs and symptoms of Rubinstein-Taybi syndrome.
Mutations in the EP300 gene cause a small percentage of cases of Rubinstein-Taybi syndrome. Like the CREBBP gene, this gene provides instructions for making a protein that helps control the activity of other genes. It also appears to be important for development before and after birth. EP300 gene mutations result in the loss of one functional copy of the gene in each cell, which interferes with normal development and causes the typical features of Rubinstein-Taybi syndrome. The signs and symptoms of this disorder caused by EP300 gene mutations are typically milder than those caused by mutations in the CREBBP gene.
Several cases of severe Rubinstein-Taybi syndrome have resulted from a deletion of genetic material from the short (p) arm of chromosome 16. Multiple genes, including the CREBBP gene, are missing as a result of this deletion. Researchers believe that the loss of multiple genes in this region probably accounts for the serious complications associated with severe Rubinstein-Taybi syndrome. Some researchers suggest that these cases are a separate condition called chromosome 16p13.3 deletion syndrome. However, a few studies indicate that some people with large deletions in the same region of chromosome 16 have characteristic features of Rubinstein-Taybi syndrome rather than a more severe condition.
Nearly 30 to 40 percent of people with Rubinstein-Taybi syndrome do not have an identified mutation in the CREBBP or EP300 gene or a chromosome 16 deletion. The cause of the condition is unknown in these cases. Researchers predict that mutations in other genes can also cause the disorder.
This condition is considered to have an autosomal dominant pattern of inheritance, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Most cases result from new mutations in the gene and occur in people with no history of the disorder in their family.
Other Names for This Condition
- Broad thumb-hallux syndrome
Additional Information & Resources
Genetic Testing Information
Genetic and Rare Diseases Information Center
Research Studies from ClinicalTrials.gov
Scientific Articles on PubMed
- Bartholdi D, Roelfsema JH, Papadia F, Breuning MH, Niedrist D, Hennekam RC, Schinzel A, Peters DJ. Genetic heterogeneity in Rubinstein-Taybi syndrome: delineation of the phenotype of the first patients carrying mutations in EP300. J Med Genet. 2007 May;44(5):327-33. Epub 2007 Jan 12. Citation on PubMed or Free article on PubMed Central
- Bartsch O, Rasi S, Delicado A, Dyack S, Neumann LM, Seemanová E, Volleth M, Haaf T, Kalscheuer VM. Evidence for a new contiguous gene syndrome, the chromosome 16p13.3 deletion syndrome alias severe Rubinstein-Taybi syndrome. Hum Genet. 2006 Sep;120(2):179-86. Epub 2006 Jun 17. Citation on PubMed
- Bartsch O, Schmidt S, Richter M, Morlot S, Seemanová E, Wiebe G, Rasi S. DNA sequencing of CREBBP demonstrates mutations in 56% of patients with Rubinstein-Taybi syndrome (RSTS) and in another patient with incomplete RSTS. Hum Genet. 2005 Sep;117(5):485-93. Epub 2005 Jul 14. Citation on PubMed
- Bentivegna A, Milani D, Gervasini C, Castronovo P, Mottadelli F, Manzini S, Colapietro P, Giordano L, Atzeri F, Divizia MT, Uzielli ML, Neri G, Bedeschi MF, Faravelli F, Selicorni A, Larizza L. Rubinstein-Taybi Syndrome: spectrum of CREBBP mutations in Italian patients. BMC Med Genet. 2006 Oct 19;7:77. Citation on PubMed or Free article on PubMed Central
- Coupry I, Roudaut C, Stef M, Delrue MA, Marche M, Burgelin I, Taine L, Cruaud C, Lacombe D, Arveiler B. Molecular analysis of the CBP gene in 60 patients with Rubinstein-Taybi syndrome. J Med Genet. 2002 Jun;39(6):415-21. Citation on PubMed or Free article on PubMed Central
- Hallam TM, Bourtchouladze R. Rubinstein-Taybi syndrome: molecular findings and therapeutic approaches to improve cognitive dysfunction. Cell Mol Life Sci. 2006 Aug;63(15):1725-35. Review. Citation on PubMed
- Hennekam RC. Rubinstein-Taybi syndrome. Eur J Hum Genet. 2006 Sep;14(9):981-5. Epub 2006 Jul 26. Review. Citation on PubMed
- Roelfsema JH, White SJ, Ariyürek Y, Bartholdi D, Niedrist D, Papadia F, Bacino CA, den Dunnen JT, van Ommen GJ, Breuning MH, Hennekam RC, Peters DJ. Genetic heterogeneity in Rubinstein-Taybi syndrome: mutations in both the CBP and EP300 genes cause disease. Am J Hum Genet. 2005 Apr;76(4):572-80. Epub 2005 Feb 10. Citation on PubMed or Free article on PubMed Central
- Rusconi D, Negri G, Colapietro P, Picinelli C, Milani D, Spena S, Magnani C, Silengo MC, Sorasio L, Curtisova V, Cavaliere ML, Prontera P, Stangoni G, Ferrero GB, Biamino E, Fischetto R, Piccione M, Gasparini P, Salviati L, Selicorni A, Finelli P, Larizza L, Gervasini C. Characterization of 14 novel deletions underlying Rubinstein-Taybi syndrome: an update of the CREBBP deletion repertoire. Hum Genet. 2015 Jun;134(6):613-26. doi: 10.1007/s00439-015-1542-9. Epub 2015 Mar 25. Citation on PubMed
- Stevens CA. Rubinstein-Taybi Syndrome. 2002 Aug 30 [updated 2019 Aug 22]. In: Adam MP, Everman DB, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2022. Available from http://www.ncbi.nlm.nih.gov/books/NBK1526/ Citation on PubMed
- Wiley S, Swayne S, Rubinstein JH, Lanphear NE, Stevens CA. Rubinstein-Taybi syndrome medical guidelines. Am J Med Genet A. 2003 Jun 1;119A(2):101-10. Review. Citation on PubMed