Confirmation study of PTEN mutations among individuals with autism or developmental delays/mental retardation and macrocephaly

Autism Res. 2010 Jun;3(3):137-41. doi: 10.1002/aur.132.


There is a strong genetic component to autism spectrum disorders (ASD), but due to significant genetic heterogeneity, individual genetic abnormalities contribute a small percentage to the overall total. Previous studies have demonstrated PTEN mutations in a sizable proportion of individuals with ASD or mental retardation/developmental delays (MR/DD) and macrocephaly that do not have features of Cowden or Bannayan-Riley-Ruvalcaba syndrome. This study was performed to confirm our previous results. We reviewed the charts of individuals who had PTEN clinical sequencing performed at our institution from January 2008 to July 2009. There were 93 subjects tested from our institution during that period. PTEN mutations were found in 2/39 (5.1%) ASD patients and 2/51 (3.9%) MR/DD patients. Three additional patients without mutations had no diagnostic information. Multiple relatives of individuals with a PTEN mutation had macrocephaly, MR, or early onset cancer (breast, renal, and prostate). Of those relatives tested, all had the familial PTEN mutation. None of the affected relatives had previously been diagnosed with Cowden or Bannayan-Riley-Ruvalcaba syndrome. We noted in our previous study several adult relatives without any findings who carried a mutation. Combined with data from our previous cohort, we have found PTEN mutations in 7/99 (7.1%) of individuals with ASD and 8/100 (8.0%) of individuals with MR/DD, all of whom had macrocephaly. We recommend testing for mutations in PTEN for individuals with ASD or MR/DD and macrocephaly. If mutations are found, other family members should be offered testing and the adults offered cancer screening if they have a PTEN mutation.

MeSH terms

  • Autistic Disorder / diagnosis
  • Autistic Disorder / genetics*
  • Cephalometry
  • Child
  • Child, Preschool
  • Comorbidity
  • Craniofacial Abnormalities / diagnosis
  • Craniofacial Abnormalities / genetics*
  • DNA Mutational Analysis*
  • Developmental Disabilities / diagnosis
  • Developmental Disabilities / genetics*
  • Female
  • Genotype
  • Humans
  • Infant
  • Intellectual Disability / diagnosis
  • Intellectual Disability / genetics*
  • Learning Disabilities / diagnosis
  • Learning Disabilities / genetics
  • Male
  • Neoplasms / diagnosis
  • Neoplasms / genetics
  • Pedigree
  • Phenotype