Multiple congenital anomalies and developmental delay in a boy associated with a de novo 16p13.3 deletion

Abstract

We describe a patient with multiple congenital anomalies including tracheobronchomalacia, CT-proven metopic craniosynostosis, glandular hypospadias and severe ventral chordee, torticollis, esotropia, strabismus, fifth finger clinodactyly, hallux valgus, and global developmental delay. Using high resolution chromosomal microarray analysis, we identified a de novo deletion of 555 kb on chromosome 16p13.3, 444 kb telomeric to the CREBBP gene and 623 kb centromeric of PKD1. Review of the literature revealed numerous reports of individuals with deletions involving adjacent regions including CREBBP, but only one overlapping with this isolated region of 16p13.3. Haploinsufficiency for one or more of the 25 candidate genes in the deleted genomic region may be responsible for these clinical features. No copy number variants (CNVs) span the entire region, but several small CNVs within the 555 kb genomic region reduce the likelihood for effects due to haploinsufficiency to 18 genes. © 2011 Wiley-Liss, Inc.