Wolfram syndrome (WFS) is a neurodegenerative disorder characterized by childhood-onset diabetes mellitus, optic nerve atrophy, diabetes insipidus, hearing impairment and commonly bladder and bowel dysfunction. We hypothesize that there is an association between smaller pons, which contains the pontine micturition center, and abnormal lower urinary tract function.
Patients with genetically confirmed WFS attend an annual multidisciplinary research clinic. Patients undergo non-invasive urodynamic testing, brain MRI and complete validated patient-reported outcome measures. Bowel and bladder diaries are filled out prior to visits. Age and sex-corrected linear and logistic mixed-effects models are used to correlate pons volume, corrected for whole brain size, to urodynamic and patient-reported outcomes.
36 patients attended 142 visits between 2010 and 2016. Mean age was 16.9 years (range 7-30) and 64% were female. Functional bladder capacity was decreased in 31%, normal in 54%, and increased in 14%. 44% and 54% had abnormal uroflowmetry and post-void residual, respectively, on at least one occasion. There was no increase over time in incidence of lower urinary tract dysfunction. Lower pons volume was associated with increased post-void residual (p = 0.048) and with higher Pediatric Incontinence Quality of Life score (p = 0.011), indicating lower quality of life and higher levels of dysfunction.
A significant number of children, adolescents and young adults with WFS have objective evidence of lower urinary tract dysfunction. Lower pons volume was associated with more abnormal urinary function and lower quality of life in WFS patients.
The Journal of urology. 2018 Jun 05 [Epub ahead of print]
Kyle O Rove, Gino J Vricella, Tamara Hershey, Muang H Thu, Heather M Lugar, Joel Vetter, Bess A Marshall, Paul F Austin