Rubinstein-Taybi syndrome associated with Chiari type I malformation caused by a large 16p13.3 microdeletion: a contiguous gene syndrome?

Rubinstein-Taybi Syndrome (RSTS, OMIM 180849) is a rare condition, which in 65% of cases is caused by haploinsufficiency of CREBBP (cAMP response element binding protein binding protein) localized to 16p13.3. A small subset of RSTS cases caused by 16p13.3 microdeletions involving neighboring genes have been recently suggested to be a true contiguous gene syndrome called severe RSTS or 16p13.3 deletion syndrome (OMIM 610543). In the present report, we describe a case of a 2-year-old female with RSTS who, besides most of the typical features of RSTS has corpus callosum dysgenesis and a Chiari type I malformation which required neurosurgical decompression. CGH microarray showed a approximately 520.7 kb microdeletion on 16p13.3 involving CREBBP, ADCY9, and SRL genes. We hypothesize that the manifestations in this patient might be influenced by the haploinsufficiency for ADCY9 and SRL.