Social, neurodevelopmental, endocrine, and head size differences associated with atypical deletions in Williams–Beuren syndrome

Michael Lugo, Zoë C. Wong, Charles J. Billington, Phoebe C.R. Parrish, Glennis Muldoon, Delong Liu, Barbara R. Pober, Beth A. Kozel

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Williams–Beuren syndrome (WBS) is a multisystem disorder caused by a hemizygous deletion on 7q11.23 encompassing 26–28 genes. An estimated 2–5% of patients have “atypical” deletions, which extend in the centromeric and/or telomeric direction from the WBS critical region. To elucidate clinical differentiators among these deletion types, we evaluated 10 individuals with atypical deletions in our cohort and 17 individuals with similarly classified deletions previously described in the literature. Larger deletions in either direction often led to more severe developmental delays, while deletions containing MAGI2 were associated with infantile spasms and seizures in patients. In addition, head size was notably smaller in those with centromeric deletions including AUTS2. Because children with atypical deletions were noted to be less socially engaged, we additionally sought to determine how atypical deletions relate to social phenotypes. Using the Social Responsiveness Scale-2, raters scored individuals with atypical deletions as having different social characteristics to those with typical WBS deletions (p =.001), with higher (more impaired) scores for social motivation (p =.005) in the atypical deletion group. In recognizing these distinctions, physicians can better identify patients, including those who may already carry a clinical or FISH WBS diagnosis, who may benefit from additional molecular evaluation, screening, and therapy. In addition to the clinical findings, we note mild endocrine findings distinct from those typically seen in WBS in several patients with telomeric deletions that included POR. Further study in additional telomeric deletion cases will be needed to confirm this observation.

Original languageEnglish (US)
Pages (from-to)1008-1020
Number of pages13
JournalAmerican Journal of Medical Genetics, Part A
Issue number5
StatePublished - May 1 2020

Bibliographical note

Funding Information:
We would like to acknowledge Drs. Joseph Dougherty and Nathan Kopp, who made helpful suggestions related to the processing of exome information to determine copy number. We also thank Drs. F. Sessions Cole and Jennifer Wambach for sharing deidentified exomes to aid in deletion size identification for the WBSCR. We would like to thank Dr. David Mills and the Medical University of South Carolina Dean's Office for overall guidance, direction, and facilitation of research time that allowed for the ability to complete this manuscript. Finally, we thank Dr. Beatrijs Lodde for editorial assistance.

Publisher Copyright:
Published 2020. This article is a U.S. Government work and is in the public domain in the USA.


  • Williams–Beuren syndrome
  • atypical deletion
  • autism spectrum
  • microcephaly
  • phenotype
  • social behavior


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