For more than a century, experts have vied to explain the cause of stuttering, the socially disabling speech disorder used to comic effect by actor Michael Palin in A Fish Called Wanda.
Theories have ranged from over-anxious parents reacting negatively to their child's developing speech to left handed children being forced to write with their right hand.
Now scientists have found that in almost one in 10 cases stuttering may be an inherited metabolic disorder that could potentially be treated with drugs.
Researchers have identified three genes which control the breakdown and recycling of substances in cells in key regions of the brain linked with speech. Two of the genes have already been linked to a serious metabolic disorder known as mucolipidosis, caused by an enzyme deficiency which has severe effects on the development of the heart, lungs, liver and joints.
Some cases of mucolipidosis can be treated with injections of enzymes and the researchers speculate that similar enzyme replacement therapy might one day be used as a treatment for stuttering too.
Michael Palin based the stuttering character Ken in A Fish Called Wanda on his father, who suffered from stammering all his life. Palin jnr was not affected though he is widely thought to have been. But he leant his name to the Michael Palin Centre for Stammering Children, founded in 1993, and remains a vice-president. The centre offers assessment and therapy for affected children.
Frances Cook, head of specialty at the centre, said the discovery of the first genes linked with stuttering "opens many new doors to understanding exactly what goes wrong during speech production."
James Battey, director of the National Institute of Deafness and Other Communication Disorders in Washington, which led the study published in the New England Journal of Medicine, said: "This is the first study to pinpoint specific gene mutations as the potential cause of stuttering, and by doing so, it might lead to a dramatic expansion in our options for treatment."
Around five per cent of children are thought to be affected by stuttering but most grow out of it, and prevalence among adults is estimated at 1 per cent. For those affected, however, it can severely hinder communication and affect their quality of life. Treatment mostly focuses on speech therapy and measures aimed at reducing anxiety, regulating breathing and improving speech fluency.
The researchers identified an area of chromosome 12 from a study of the genetic make-up of 46 families in Pakistan affected by stuttering. They found the same mutations in some of 270 individuals from Britain and the US who stuttered. Overall, they estimate 9 per cent of people who stutter have mutations in one of the three genes.
Not all those with the genetic mutations were affected by stuttering, indicating that additional causes must be at work. A worldwide epidemiological study to establish the percentage of people who carry one or more of the mutations is now under way. The researchers are also conducting biochemical studies to determine how the mutations affect the enzymes.
An editorial in the NEJM says the biological pathway uncovered is an "unlikely culprit" for stuttering and a "remarkable feature" of the study. It concludes: "The task of joining the dots between genes and stuttering is just beginning."