Rubinstein-Taybi syndrome: New neuroradiological and neuropsychiatric insights from a multidisciplinary approach

Am J Med Genet B Neuropsychiatr Genet. 2018 Jun;177(4):406-415. doi: 10.1002/ajmg.b.32628. Epub 2018 Apr 10.

Abstract

Rubinstein-Taybi syndrome is a rare, autosomal dominant, plurimalformative disorder that is clinically characterized by intellectual disability and a wide spectrum of congenital anomalies; facial dysmorphisms are typical, and broad thumbs and great toes are particularly distinctive. Its genetic basis is only partially known, with a detection rate of approximately 65-70%; specifically, microdeletions or mutations in the CREBBP or EP300 genes can be found. Much is known about its clinical features and health-care protocols, but some areas of clinical knowledge are currently unsolved. In particular, few efforts have been made until now to understand the variability in the neuropsychological and neurobehavioral profile and to deepen knowledge of the neuroradiological malformative pattern. Consequently, little is known about the possible genotype-phenotype correlations of these issues. Here, we report clinical and genetic data from a cohort of 23 RSTS Italian patients. The most common features in brain magnetic resonance imaging (MRI) were dysmorphic aspects of the corpus callosum (73.6%) with or without minor dysmorphisms of cerebellar vermis, periventricular posterior white matter hyperintensity, and other less common anomalies. The most interesting feature on the whole spine MRI scans was the tendency for a low-lying conus medullaris without terminal filum thickening. These data will help to improve neuropsychiatric and neuroradiological knowledge and highlight specific genotype-phenotype correlations.

Keywords: CREBBP gene; EP300 gene; MRI anomalies; RSTS; behavioral phenotype; intellectual disability; tethered cord.

MeSH terms

  • Adolescent
  • Brain / diagnostic imaging
  • CREB-Binding Protein / genetics
  • Child
  • Child, Preschool
  • Cohort Studies
  • E1A-Associated p300 Protein / genetics
  • Female
  • Genetic Association Studies
  • Humans
  • Infant
  • Italy
  • Magnetic Resonance Imaging
  • Male
  • Mutation
  • Neuropsychiatry / methods
  • Phenotype
  • Rubinstein-Taybi Syndrome / genetics*
  • Rubinstein-Taybi Syndrome / physiopathology*
  • Young Adult

Substances

  • CREB-Binding Protein
  • CREBBP protein, human
  • E1A-Associated p300 Protein
  • EP300 protein, human