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.
- broad thumb-hallux syndrome