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By Sean Henahan, Access Excellence

COPENHAGEN The identification of a genetic marker for nocturnal enuresis (bed-wetting) could lead to better diagnosis and treatment of this common disorder, according to Danish researchers.

A team of Danish scientists examined 400 Danish families and selected 11 that suffered from 'primary nocturnal enuresis type 1' (PEN1). PEN1 is characterized by three or more nightly episodes in children that are at least seven years old, where the child has always had the problem.

The researchers observed that more than 90 percent of families with a history of PNE expressed a specific genetic marker. They were able to localize the responsible gene to the long arm of chromosome 13.

"A child who wets the bed does not do so on purpose," said Hans Eiberg, Associate Professor at the Danish Center for Genome Research. "We now have scientific evidence that many cases of bed-wetting are caused by genetic factors beyond a child's and parent's control."

Identifying the gene responsible for nocturnal enuresis should greatly facilitate the understanding and treatment of this emotionally debilitating disorder. A variety of potential candidate genes have been named, including genes involved in decreasing the amount of urine output during the night and neuroreceptor genes that control such various activities as smooth muscle contraction and sleep activity. However, none of these appear to lie in the relevant region.

This is a significant development in the evaluation and treatment of a condition that affects many children," said Marc Cendron, M.D., Pediatric Urologist at Dartmouth-Hitchcock Medical Center. "Its impact will be greatest for the estimated five to seven million American children above age six who suffer from PNE. For such children, bed-wetting is a frustrating condition which can be devastating to their self-esteem and very disruptive to their family life."

A potential genetic component in PNE was proposed 20 years ago. Traditionally, bedwetting among children has been considered a manifestation of emotional problems. The current research is bound to change this perception. Recent medical research has established a link between PNE and deficient production of antidiuretic hormone (ADH), which controls urine production.

"There are two types of nocturnal enuresis. Primary enuresis, the most prevalent, refers to children over the age of six who have never achieved dryness for an extended period of time. Secondary enuresis, often associated with emotional stress or medical illness, is the recurrence of bed-wetting in children who have been dry for six months or longer.

"While we suspected PNE was hereditary, this is the first time a direct genetic link has been identified," said Dr. Cendron. "I believe the data in Nature Genetics may lay the groundwork for a large-scale genetics study to identify the PNE gene."

Previous studies suggest that if both parents have a history of bed-wetting, their children will have a 68 percent chance of being bed-wetters. If only one parent was a bed-wetter, a child has a 44 percent chance of being a bed-wetter. The studies also suggest only a 15 percent chance of a child being a bed-wetter if neither parent has a history of the problem.

"Children with PNE often experience feelings of guilt and embarrassment. This, compounded by a social stigma and misunderstanding of the condition, often results in underdiagnosis, undertreatment, and needless suffering by children and their families. In fact, a 1989 Journal of Pediatrics article reports that 33 percent of parents deal with the condition by punishment or humiliation. This is unfortunate. It is important that parents speak to a physician about bed-wetting. There are safe and effective treatments available," emphasized William Cromie, M.D., Chief, Section of Pediatric and Reconstructive Urology and Vice Chairman, Department of Surgery, at the University of Chicago.

"With the recognition of a genetic marker for enuresis, the approach to treating PNE may be simplified," said Dr. Cromie. "Patients may be identified and treated at an earlier age, which could spare them the psychosocial effects that can result from this widespread and often misunderstood disorder."

The Danish study appeared in the July 1, 1995 issue of the international journal Nature Genetics.

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