Potocki-Shaffer syndrome in a child without intellectual disability-The role of PHF21A in cognitive function

Am J Med Genet A. 2017 Mar;173(3):716-720. doi: 10.1002/ajmg.a.37988. Epub 2017 Jan 27.


Potocki-Shaffer syndrome is a contiguous gene deletion syndrome involving 11p11.2p12 and characterized by multiple exostoses, biparietal foramina, genitourinary anomalies in males, central nervous system abnormalities, intellectual disability, and craniofacial abnormalities. Current literature implicates haploinsufficiency of three genes (ALX4, EXT2, and PHF21A) in causing some of the cardinal features of PSS. We report a patient with multiple exostoses, biparietal foramina, and history of mild developmental delay. Cognitive and behavioral testing supported formal diagnoses of anxiety, verbal dyspraxia, articulation disorder, and coordination disorder, without intellectual disability. His facial features, though distinctive, were not typical of those observed in PSS. As the chromosomal deletion does not encompass PHF21A, this case lends further support that haploinsufficiency of PHF21A contributes to the intellectual disability and craniofacial abnormalities in PSS and that there are other genes in the region which likely contribute to the behavioral phenotype in this syndrome. © 2017 Wiley Periodicals, Inc.

Keywords: PHF21A; Potocki-Shaffer syndrome; RAG1; contiguous gene deletion syndrome; multiple exostoses.

Publication types

  • Case Reports

MeSH terms

  • Child, Preschool
  • Chromosome Banding
  • Chromosome Deletion
  • Chromosome Disorders / diagnosis*
  • Chromosome Disorders / genetics*
  • Chromosome Mapping
  • Chromosomes, Human, Pair 11 / genetics
  • Cognition*
  • Comparative Genomic Hybridization
  • Exostoses, Multiple Hereditary / diagnosis*
  • Exostoses, Multiple Hereditary / genetics*
  • Gene Deletion
  • Genetic Association Studies
  • Haploinsufficiency
  • Histone Deacetylases / genetics*
  • Humans
  • Male
  • Phenotype*
  • Radiography


  • PHF21A protein, human
  • Histone Deacetylases

Supplementary concepts

  • Potocki-Shaffer syndrome