Case Report
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World J Gastroenterol. Sep 14, 2010; 16(34): 4363-4366
Published online Sep 14, 2010. doi: 10.3748/wjg.v16.i34.4363
Therapy-refractory gastrointestinal motility disorder in a child with c-kit mutations
Christian Breuer, Jun Oh, Gerhard J Molderings, Michael Schemann, Birgit Kuch, Ertan Mayatepek, Rüdiger Adam
Christian Breuer, Jun Oh, Ertan Mayatepek, Rüdiger Adam, Department of General Pediatrics, University Children’s Hospital, 40225 Düsseldorf, Germany
Jun Oh, Department of Pediatric Nephrology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
Gerhard J Molderings, Institute of Human Genetics, University Hospital Bonn, 53127 Bonn, Germany
Michael Schemann, Birgit Kuch, Department of Human Biology, Technische Universität München, 85350 Freising-Weihenstephan, Germany
Rüdiger Adam, Pediatric Gastroenterology, Department of Pediatrics, University Hospital Mannheim, 68167 Mannheim, Germany
Author contributions: Breuer C and Adam R contributed equally to this work and performed the research; Adam R, Oh J and Mayatepek E designed the research; Molderings GJ performed the mutational analysis of c-kit; Scheman M and Kuch B performed the immunohistochemistry; Breuer C wrote the paper.
Correspondence to: Dr. Christian Breuer, MD, Department of General Pediatrics, University Children’s Hospital, Moorenstr. 5, 40225 Düsseldorf, Germany.
Telephone: +49-211-8117687 Fax: +49-211-8119276
Received: April 6, 2010
Revised: June 4, 2010
Accepted: June 11, 2010
Published online: September 14, 2010

Constipation and fecal impaction are frequent and distressing complaints in pediatric gastroenterology. Especially in neurologically handicapped children, treatment of severe forms of slow-transit constipation (STC) can be difficult. In the majority of cases, STC is of unknown etiology. However, in recent years, there is growing evidence that interstitial cells of Cajal (ICCs), which serve as electrical pacemakers and generate spontaneous electrical slow waves in the gastrointestinal tract, might play an important role in the pathophysiology of STC. It remains unclear whether morphological ICC alterations seen in affected patients are based on congenital developmental anomalies, or whether they are a consequence of long-term constipation with secondary damage of the gastrointestinal nervous system. To the best of our knowledge, we present the first case of a patient with histological alterations in ICC morphology who displayed multiple alterations of c-kit at the level of mRNA. The protein encoded by c-kit is the receptor tyrosine kinase Kit (CD117), which is crucial for development and function of ICCs. Therefore, these findings provide a new explanation for congenital alterations of ICC development that result in gastrointestinal motility disorders.

Keywords: Slow-transit constipation, Interstitial cells of Cajal, c-kit