Children's Hospital Boston George O'Brien Urology Research Center

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DESCRIPTION (provided by applicant): Overactive bladder (OAB), also known as detrusor overactivity (a cystometric term), urge syndrome, or overactive bladder syndrome, is the most common voiding dysfunction in children. While its etiology and underlying pathophysiology remains elusive, the clinical presentation runs across a spectrum: from slow and insidious onset with a gradual increase in the strength of the urge, to voiding that can occur during a long period of time, to sudden, dramatic episodes of incontinence in children who were normally dry over a brief period of time. Based on the Urologic Diseases in America analysis of physicians in office-based settings there were 1,781,506 visits to pediatricians and family practitioners for which urinary incontinence was coded as any diagnosis for 1992-2000, a rate of 2,548 per 100,000 children. A total of 1,126,911 office visits were made by children with a primary diagnosis of incontinence, a rate of 1,612 per 100,000 children. Two recent studies highlight the importance of recognizing and treating pediatric OAB as a precursor to adult OAB and painful bladder syndrome/interstitial cystitis (PBS/IC). One reports that pediatric benign daytime frequency syndrome and nocturnal enuresis were associated with a more than a two-fold increase in adult urge incontinence. Similarly, a second study found a higher prevalence of childhood voiding dysfunction in 170 women with urinary frequency, urgency, stress incontinence and urge incontinence. The overall goals of Project 1 are: 1) To use novel approaches to understand the genetic basis of pediatric OAB, 2) To identify and perform linkage analysis in families with multiple affected members, and 3) To identify candidate genes containing mutations that result in OAB. We plan to attain our goals via the following specific aims: Aim 1. Recruit extended families with multiple affected members of children diagnosed with OAB. Aim 2. Map the locations of OAB genes by: a) performing targeted mutation analysis of candidate genes we have previously identified in the adult population with urgency and frequency as candidate OAB genes in our pediatric population and b) by linkage analysis in families in which OAB is segregating. Aim 3. Identify within linked regions of the genome those genes which harbor mutations that cause OAB and correlate the types of mutations with clinical symptoms. The overall goal will be to identify genetic risk factors for OAB and use this information for improved diagnosis and possible therapeutic intervention.