Findings suggest common speech problem, in some cases, may actually be an inherited metabolic disorder

Stuttering may be the result of a glitch in the day-to-day process by which cellular components in key regions of the brain are broken down and recycled, says a study in the Feb. 10 Online First issue of the New England Journal of Medicine.

This is a very exciting discovery , said National Stuttering Association (NSA) Chairman Ernie Canadeo. "It validates our view that stuttering has a genetic component, and that people who stutter can't help it. Its part of their genes.  I am proud that our organization and its members particapted in this important study."

The study, led by researchers at the National Institute on Deafness and Other Communication Disorders (NIDCD), part of the National Institutes of Health, has identified three genes as a source of stuttering in volunteers in Pakistan, the United States, and England. Mutations in two of the genes have already been implicated in other rare metabolic disorders also involved in cell recycling, while mutations in a third, closely related, gene have now been shown to be associated for the first time with a disorder in humans.

The study provides further evidence that stuttering is not a behavioral disorder but has as its origins, genetics manifesting in abnormal neuronal activity. We have learned much recently from brain imaging and pharmacologic studies that stuttering is associated with abnormal neurophysiology--how this relates directly to lysosomal function is an area which we definitely need to research further, said Gerald A. Maguire, M.D. Associate Professor of Clinical Psychiatry Kirkup Chair in Stuttering Treatment, Senior Associate Dean, Educational Affairs, University of California, Irvine School of Medicine.

"For hundreds of years, the cause of stuttering has remained a mystery for researchers and health care professionals alike, not to mention people who stutter and their families," said James F. Battey, Jr., M.D., Ph.D., director of the NIDCD. "This is the first study to pinpoint specific gene mutations as the potential cause of stuttering, a disorder that affects 3 million Americans, and by doing so, might lead to a dramatic expansion in our options for treatment."

Stuttering tends to run in families, and researchers have long suspected a genetic component. Previous studies of stuttering in a group of families from Pakistan had been done by Dennis Drayna, Ph.D., a geneticist with the NIDCD, which indicated a place on chromosome 12 that was likely to harbor a gene variant that caused this disorder.

In the latest research, Dr. Drayna and his team refined the location of this place on chromosome 12 and focused their efforts on the new site. They sequenced the genes surrounding a new marker and identified mutations in a gene known as GNPTAB in the affected family members. The GNPTAB gene is carried by all higher animals, and helps encode an enzyme that assists in breaking down and recycling cellular components, a process that takes place inside a cell structure called the lysosome.

They then analyzed the genes of 123 Pakistani individuals who stutter-46 from the original families and 77 who are unrelated-as well as 96 unrelated Pakistanis who don't stutter, and who served as controls. Individuals from the United States and England also took part in the study, 270 who stutter and 276 who don't. The researchers found some individuals who stutter possessed the same mutation as that found in the large Pakistani family. They also identified three other mutations in the GNPTAB gene which showed up in several unrelated individuals who stutter but not in the controls.

These findings will help with early identification of stuttering so children can get the therapy and support they need at an early age, which can often lead to a better outcomes", said John A. Tetnowski, Ph. D, CCC-SLP, Director of Communicative Disorders, University of Louisiana at Lafayette and an NSA Board Member.

Dr. Drayna and Dr. McGuire gave presentations, moderated by Dr. Tetnowski, at the National Stuttering Association Research Symposium in Arizona last year and are scheduled to present the implications of these new findings on people who stutter at the NSA Conference and Research Symposium in Cleveland this July. Over 600 people who stutter, their families, speech language pathologists, and others interested in stuttering typically attend the conference each year.

Stuttering is a speech disorder in which a person repeats or prolongs sounds, syllables, or words, disrupting the normal flow of speech. It can severely hinder communication and a person's quality of life. Most children who stutter will outgrow stuttering, although many do not; roughly 1 percent of adults stutter worldwide. Current therapies for adults who stutter have focused on such strategies as reducing anxiety, regulating breathing and rate of speech, and using electronic devices to help improve fluency.

The National Stuttering Association is a non-profit organization dedicated to bringing hope and empowerment to children and adults who stutter, their families, and professionals through support, education, advocacy, and research. It is represented by over 100 local chapters and support programs for children, families, teens, and adults throughout the United States. It was established in 1977.