Rubinstein-Taybi Syndrome – Causes and Treatments

Rubinstein-Taybi Syndrome (see here) is an autosomal recessive genetic disorder characterized by average height, average intelligence, mild to moderate intellectual disability, wide to very wide first toes and fingers, broad hands, and unusually small thumbs. Additional characteristics of this disorder include heart and kidney problems, eye defects, cleft pallet, cleft lip, and hypothyroidism. Most people with RTS have a history of developmental delays, brain injury, and birth defects. Some children are born with normal ears but have a genetic predisposition to deafness.

Rubinstein-Taybi Syndrome affects approximately 5 percent of the population in the United States. The average age of onset of RTS is between three and four years of age. Early symptoms include mental retardation, poor development of muscular coordination, poor vision, and poor hearing. Developmental delays are present even before the onset of physical symptoms. Most children with RTS have poor muscle tone and appear clumsy.

Rubinstein-Taybi Syndrome occurs due to mutations in the genes encoding the transcription factor known as PRDM8. The deletion of one of the PRDM8 genes results in severe genetic retardation. Because most individuals who suffer from Rubinstein-Taybi Syndrome do not carry any copy of the PRDM8 gene, they have normal or slightly delayed growth and development. Children with Rubinstein-Taybi Syndrome often have low birth weights and abnormal heart rhythms.

Rubinstein-Taybi Syndrome is a complex genetic disorder. The exact cause of this genetic disorder is not known, although geneticists suggest that it is influenced by the premature duplication of chromosome segments in the mother’s womb, leading to two or more copies of chromosome segments becoming active during embryonic development. Most children affected with Rubinstein-Taybi Syndrome have a history of prenatal and neonatal defects such as heart or kidney problems and premature births. Rubinstein-Taydi Syndrome is believed to be inherited via de novo mutations, meaning mutations which occur naturally without the intervention of any other genes. Although many RTS patients have other genetic disorders, researchers have identified only three rare de novo mutations that appear to be responsible for this autosomal recessive genetic disorder.

Researchers are still searching for additional genetic causes of Rubinstein-Taydi Syndrome, however, the most likely causes are mutations in the genes encoding the FMR1 and PRDM8 transcription factors. In order to test the hypothesis that Rubinstein-Taydi Syndrome may be inherited through de novo mutations, investigators use DNA from unaffected family members and unaffected sibling pairs. If mutations are found in either the PRDM8 gene or the FMR1 gene, researchers will then need to test them in mice. If de novo mutations are the origin of Rubinstein-Taydi Syndrome, it is likely that an affected child will inherit an additional genetic abnormality from either the father or mother, resulting in a new syndrome. If mutations are identified in either the PRDM8 gene or the FMR1 gene, researchers will study related genetic conditions in mice to identify potential causes of de novo mutations and the genes involved. If mutations are present in both the PRDM8 gene and the FMR1 gene, investigators will conduct studies of families with unaffected brothers and sisters, testing for related mutations.

Although scientists do not understand the exact genetic causes of Rubinstein-Taydi Syndrome, they do know a great deal about the underlying mechanisms. Geneticists have identified several genes that play an important role in the regulation of multiple genes. By determining the genetic basis of de novo mutations in the FMR1 and PRDM8 genes, researchers will be able to develop new treatments to alleviate the symptoms of this rare genetic disorder.