Duplications of the critical Rubinstein - Taybi deletion region on chromosome 16p13.3 cause a novel recognisable syndrome

Bernard Thienpont, Frédérique Béna, Jeroen Breckpot, Nicole Philip, Björn Menten, Hilde Van Esch, Emmanuel Scalais, Jessica M. Salamone, Chin To Fong, Jennifer L. Kussmann, Dorothy K. Grange, Jerome L. Gorski, Farah Zahir, Siu Li Yong, Michael M. Morris, Stefania Gimelli, Jean Pierre Fryns, Geert Mortier, Jan M. Friedman, Laurent VillardArmand Bottani, Joris R. Vermeesch, Sau Wai Cheung, Koen Devriendt

Research output: Contribution to journalArticlepeer-review

46 Scopus citations


Background: The introduction of molecular karyotyping technologies facilitated the identification of specific genetic disorders associated with imbalances of certain genomic regions. A detailed phenotypic delineation of interstitial 16p13.3 duplications is hampered by the scarcity of such patients. Objectives: To delineate the phenotypic spectrum associated with interstitial 16p13.3 duplications, and perform a genotype-phenotype analysis. Results: The present report describes the genotypic and phenotypic delineation of nine submicroscopic interstitial 16p13.3 duplications. The critically duplicated region encompasses a single gene, CREBBP, which is mutated or deleted in Rubinstein - Taybi syndrome. In 10 out of the 12 hitherto described probands, the duplication arose de novo. Conclusions: Interstitial 16p13.3 duplications have a recognizable phenotype, characterized by normal to moderately retarded mental development, normal growth, mild arthrogryposis, frequently small and proximally implanted thumbs and characteristic facial features. Occasionally, developmental defects of the heart, genitalia, palate or the eyes are observed. The frequent de novo occurrence of 16p13.3 duplications demonstrates the reduced reproductive fitness associated with this genotype. Inheritance of the duplication from a clinically normal parent in two cases indicates that the associated phenotype is incompletely penetrant.

Original languageEnglish
Pages (from-to)155-161
Number of pages7
JournalJournal of Medical Genetics
Issue number3
StatePublished - Mar 2010


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