Otopalatodigital 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 (2,3)
  • 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%) (1)
  • 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 (1)
    • in a study by Wallerstein et al (4), growth retardation, nevus flammeus, coloboma, and hypotonia were found to have positive predictive value for the presence of deletion

Reference:

1. Balci S et al. A 15-year-old boy with Rubinstein-Taybi syndrome associated with severe congenital malalignment of the toenails. Pediatr Dermatol. 2004 Jan-Feb;21(1):44-7.
2. Marion RW et al. Apparent dominant transmission of the Rubinstein-Taybi syndrome. Am J Med Genet. 1993 May 15;46(3):284-7.
3. Brewster TG et al.Oto-palato-digital syndrome, type II--an X-linked skeletal dysplasia.Am J Med Genet. 1985 Feb;20(2):249-54.
4. 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.