More Than Half of Severe Mental Disability Cases Not Inherited: Study

THURSDAY Sept. 27, 2012 -- More than half of the cases of severe intellectual disability are the result of random genetic mutations that are not passed down from parents, researchers from Switzerland and Germany report.

Severe intellectual disability, also known as nonsyndromic mental retardation, is the most common form of mental retardation. Children or adults with the condition have no physical abnormalities, but have IQs of less than 50. It affects up to 2 percent of kids worldwide.

The new study, which appears online Sept. 27 in The Lancet, suggests that many of the gene variants associated with the condition show up for the first time in the affected children.

"The majority of patients with severe intellectual disability are due to gene mutations that are not present in the parents," said study author Dr. Anita Rauch, a researcher at the Institute of Medical Genetics in Zurich. "In the majority of cases, the recurrence risk within the family is low, which is usually a big relief for the parents and encourages them to have further children."

Researchers from the German Mental Retardation Network used a new gene sequencing technique to look for mutations in 51 children with unexplained intellectual disability and their unaffected parents. According to the report, children with intellectual disability carried a significantly higher number of potentially disease-causing genes than those without the disorder. New mutations in 11 known and six new candidate genes were estimated to cause intellectual disability in up to 55 percent of the children, the study authors reported.

In the future, Rauch said, "identification of subgroups of patients with a certain defect may soon lead to a better understanding of the respective natural course, which may then lead to a better disease management by earlier recognition of accompanying complications." As it stands, children and adults with nonsyndromic mental retardation are treated only with "supportive education and supportive treatment of complications such as epilepsy," she added.

Commenting on the findings, Dr. Marshall Summar, chief of genetics and metabolism at Children's National Medical Center in Washington, D.C., said: "This study drills down even deeper into our understanding of nonsyndromic mental retardation. This doesn't change how you treat the child, but it gives us a few more clues into what is involved."

The findings are reassuring for parents concerned that future children will also be affected, Summar noted. However, "the chance is not zero, the genes may be in the parents' testes or ovaries, so there is still a chance that it is passed down from parents and may affect other children in the family," he said. "The risk is low, but it's not zero."

Dr. Andrew Adesman, chief of developmental and behavioral pediatrics at Steven and Alexandra Cohen Children's Medical Center of New York in New Hyde Park, pointed out that the new genetic screening tests and technologies are more sophisticated than older versions. "We can't rely upon physical signs of a genetic disorder to suggest gene testing," he said. "We should implement universal genetic testing for all kids with unexplained intellectual disability and/or severe forms of autism," he suggested.

"The fact that the genes do not seem to be passed down from parents may prove reassuring," Adesman said. "When families have a child with severe intellectual disability or autism, they may have concerns about the recurrence risk or whether it was caused by something that they did during the pregnancy, but this is reassuring that they can have other children and not be worried about increased risk for another similarly affected child."

Doctors were unable to give parents this type of reassurance before the advent of new gene testing technologies, Adesman explained.

More information

To learn more about intellectual disability, visit the Nemours Foundation.

Posted: September 2012


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