A familial contiguous gene deletion syndrome at Xp22.3 characterized by severe learning disabilities and ADHD

Am J Med Genet A. 2003 Oct 1;122A(2):139-47. doi: 10.1002/ajmg.a.20231.


We describe a mother and two sons with a 6-Mb terminal deletion of the short arm of the X chromosome. The breakpoint was localized to a region between DXS6837 and sAJ243947 in Xp22.33. The two boys were shown to be deleted for the SHOX and ARSE genes on their X chromosome. Both sons were short in stature and showed mild to moderate skeletal abnormalities. The most significant findings in the younger son were severe learning disabilities and attention deficit hyperactivity disorder (ADHD). The older son tested in the mild mental retardation range and was also affected by ADHD. The VCX-A gene, implicated recently in X-linked nonspecific mental retardation, was found to be present in both boys. The mother's stature was greater than one standard deviation below her target height and she had only subtle radiographic evidence of Madelung deformity. Our findings indicate that loss of the Xp22.3 region is not always associated with the classic presentations of Léri-Weill syndrome, or chondrodysplasia punctata, and that one or more genes involved in learning and attention may reside in Xp22.3.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Attention Deficit Disorder with Hyperactivity / genetics*
  • Chromosomes, Human, X*
  • Cytogenetic Analysis
  • Family Health
  • Female
  • Gene Deletion*
  • Humans
  • Intellectual Disability / genetics*
  • Karyotyping
  • Learning Disabilities / genetics*
  • Male
  • Pedigree
  • Syndrome