Phenotypic expansion of the interstitial 16p13.3 duplication: A case report and review of the literature

• Our study provides additional evidence to 16p13.3 duplications as a novel syndrome.
• Our study expands the phenotypic spectrum correlated with the proposed syndrome.
• Different sizes of the duplication including CREBBP present variable malformations.
• This is the second report of 16p13.3 duplications in Asian population.

Genotype–phenotype analysis of at least 25 individuals with interstitial 16p13.3 duplications defines a recognizable syndrome associated with duplication of a critical Rubinstein–Taybi region encompassing only the CREBBP gene. Nevertheless, variable or incompletely penetrant phenotype has been reported previously. We here report a case of a 5-year old boy with a recognizable phenotype of this syndrome, including intellectual disability, mild arthrogryposis, small and proximally implanted thumbs and characteristic facial features. In addition, growth delay, microcephaly and distinguishable structural brain MRI abnormalities were observed. A de novo 1.5 Mb interstitial duplication of 16p13.3 was detected by SNP-array and fluorescence in situ hybridization (FISH). Short tandem repeat polymorphism (STRP) analysis with marker D16S475 indicated that the duplication was formed before maternal meiosis II. Our findings highlight the variable clinical features and further expand the phenotypic spectrum correlated with this lately proposed syndrome.