Rubinstein-Taybi syndrome

Rubinstein-Taybi syndrome (RTS):

• is a rare disorder characterized by mental and physical retardation, typical facies, and short and broad thumbs and halluces (1)
  • a reported incidence of 1 in 125 000 people
  • also cardiac, neurologic, ocular, and skeletal abnormalities may occur
• aetiology of RTS has recently been clarified
  • previously this disorder was previously believed to be inherited as X-linked with heterozygous females being more mildly affected
  • an autosomal dominant mutation is now believed to be the most probable cause of RTS
    • in studies, many RTS patients have been shown to have molecular mutations or microdeletions of chromosome 16p13.3. This region contains the gene for the human cAMP response element binding (CREB) protein (CBP)
      • CBP is an important regulatory protein within the cell and interacts with a myriad of other such proteins
    • however this mutation or microdeletion is only found in a minority of RTS cases (4-25%)
  • except for rare cases, no phenotype-genotype correlation between RTS patients with or without deletion was detected and therefore normal fluorescent in situ hybridization (FISH) results, do not exclude the diagnosis of RTS
    • in a study by Wallerstein et al (2), growth retardation, nevus flammeus, coloboma, and hypotonia were found to have positive predictive value for the presence of deletion

Reference:

1. Milani D et al. Rubinstein-Taybi syndrome: clinical features, genetic basis, diagnosis, and management. tal J Pediatr. 2015 Jan 20:41:4.
2. Wallerstein R, Anderson CE, Hay B, et al. Submicroscopic deletions at 16p13.3 in Rubinstein-Taybi syndrome: frequency and clinical manifestations in a North American population. J Med Genet 1997;34: 203-206.