Rare genomic rearrangement in a boy with Williams-Beuren syndrome associated to XYY syndrome and intriguing behavior

Am J Med Genet A. 2015 Dec;167A(12):3197-203. doi: 10.1002/ajmg.a.37360. Epub 2015 Sep 30.

Abstract

Williams-Beuren syndrome (WBS) is caused by a hemizygous contiguous gene microdeletion of 1.55-1.84 Mb at 7q11.23 region. Approximately, 28 genes have been shown to contribute to classical phenotype of SWB with presence of dysmorphic facial features, supravalvular aortic stenosis (SVAS), intellectual disability, and overfriendliness. With the use of Microarray-based comparative genomic hybridization and other molecular cytogenetic techniques, is possible define with more accuracy partial or atypical deletion and refine the genotype-phenotype correlation. Here, we report on a rare genomic structural rearrangement in a boy with atypical deletion in 7q11.23 and XYY syndrome with characteristic clinical signs, but not sufficient for the diagnosis of WBS. Cytogenetic analysis of G-banding showed a karyotype 47,XYY. Analysis of DNA with the technique of MLPA (Multiplex Ligation-dependent Probe Amplification) using kits a combination of kits (P064, P036, P070, and P029) identified an atypical deletion on 7q11.23. In addition, high resolution SNP Oligonucleotide Microarray Analysis (SNP-array) confirmed the alterations found by MLPA and revealed others pathogenic CNVs, in the chromosomes 7 and X. The present report demonstrates an association not yet described in literature, between Williams-Beuren syndrome and 47,XYY. The identification of atypical deletion in 7q11.23 concomitant to additional pathogenic CNVs in others genomic regions allows a better comprehension of clinical consequences of atypical genomic rearrangements.

Keywords: 47,XYY syndrome; 7q11.23; Williams syndrome; atypical deletion; behavioral phenotype; genomic rearrangement.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Attention Deficit Disorder with Hyperactivity / genetics*
  • Attention Deficit Disorder with Hyperactivity / pathology
  • Child, Preschool
  • Chromosome Deletion*
  • Chromosomes, Human, Pair 7 / genetics*
  • Comparative Genomic Hybridization
  • DNA Copy Number Variations
  • Gene Rearrangement*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Male
  • Multiplex Polymerase Chain Reaction
  • Phenotype
  • Prognosis
  • Sex Chromosome Disorders / genetics*
  • Williams Syndrome / genetics*
  • Williams Syndrome / pathology
  • XYY Karyotype / genetics*

Supplementary concepts

  • 47, XYY syndrome