Studies Help Confirm Gene Mutations Related to Autism Spectrum Disorders

Research from Nationwide Children’s Hospital is providing clues to the genetic elements of autism spectrum disorders with findings that could play an important role in genetic counseling.

According to the Centers for Disease Control and Prevention, autism spectrum disorders, including “classic” autism, pervasive developmental delay, and Asperger syndrome, affect an estimated 1 in 150 children.  Much evidence supports the idea that genetic factors are one of the main underlying causes of autism spectrum disorders.  Recently, several cases of mutations in the PTEN gene have been detected in children with autism spectrum disorders and macrocephaly (an abnormally large head size).  It is already known that mutations in the PTEN gene are found in specific families predisposed to certain types of cancer, and in some types of mental retardation/developmental delay syndromes. However, no systematic study had been performed in a group of children with autism.

“We had no idea how common PTEN mutations were in children with autism spectrum disorders. It is important to find out how frequently this occurs, and to define any features that might be identified clinically in those with autism and a PTEN mutation, such as large head size,” said Kim McBride, MD, principal investigator in the Center for Molecular and Human Genetics and one of the study authors.  “This will guide physicians on whether this should be part of their routine work-up for autism spectrum disorders, and which individuals should be tested for mutations in this gene.”

PTEN Gene as Autism Diagnostic Tool
To help clarify the role of PTEN mutations in autism spectrum disorders, developmental delay, mental retardation and macrocephaly, investigators in the Center for Molecular and Human Genetics at The Research Institute examined the medical records of 114 patients who were tested clinically for PTEN mutations during a three year period.  Sixty children with autism spectrum disorders being evaluated at Nationwide Children’s Hospital received PTEN genetic testing. The patients’ genetic data was then correlated with their clinical data including current and past medical diagnoses, findings on physical exam, genetic test results and family history.

The study identified mutations among 8.3 percent of the patients with autism spectrum disorders and macrocephaly, several mutations of which were newly reported. These data indicate that evaluation of the PTEN gene could serve as a valuable diagnostic tool for patients referred to genetics, developmental pediatric and neurology clinics for evaluation of autism spectrum disorders.

Although large prospective studies will be needed to elucidate the true prevalence of these mutations, this study emphasizes the importance of genetic testing guidelines. 

Importance in Genetic Counseling
“It is becoming clear that PTEN mutations could contribute to the development of autism spectrum disorders in a subset of patients,” said Research Genetic Counselor Elizabeth Varga, MS, and one of the study’s authors.  “Discovery of a PTEN mutation can help a family understand why their child developed an autism spectrum disorder, and can also provide important information for counseling and management. PTEN mutations are inherited from a parent about 50 percent of the time and since people with PTEN mutations have a higher chance of developing certain cancers, discovery of this mutation may allow for early cancer surveillance and prevention in the child and potentially, family members.”