Confirmation study of PTEN mutations among individuals with autism or developmental delays/mental retardation and macrocephaly.
PTEN mutations show up in about 1 in 13 clients who have autism or developmental delay plus macrocephaly, so send them for genetic testing.
01Research in Context
What this study did
The team looked for PTEN gene changes in people with autism or developmental delay who also had big heads.
They tested a small group already seen in genetics clinics.
All participants had head sizes above the 97th percentile for their age.
What they found
About 7 in every 100 people with autism plus macrocephaly had a PTEN mutation.
The rate was 8 in 100 for those with general developmental delay and macrocephaly.
Because PTEN carriers face higher cancer risk, the authors say genetic testing should be routine for these clients.
How this fits with other research
McMillan et al. (1999) first showed that roughly 1 in 6 autistic children have macrocephaly, giving the baseline that Hilton et al. (2010) used to target testing.
Cederlund et al. (2014) seems to disagree, finding only 3% macrocephaly in a preschool community sample. The gap disappears when you note that clinic samples catch more severe cases, while population studies include milder ones.
Hong et al. (2021) found an 11% diagnostic yield from chromosomal microarray in non-syndromic developmental delay with macrocephaly, matching the 7-8% PTEN hit rate and reinforcing the rule: big head plus delay equals genetic work-up.
Why it matters
If your client has autism or developmental delay and a head size above the 97th percentile, add PTEN testing to the medical referral. A positive result changes care: families need cancer surveillance and you gain a clear genetic explanation for the child's profile.
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02At a glance
03Original abstract
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.
Autism research : official journal of the International Society for Autism Research, 2010 · doi:10.1002/aur.132