Abstract
A boy showing symptoms of a Turcot-like childhood cancer syndrome together with stigmata of neurofibromatosis type I is reported. His brother suffers from an infantile myofibromatosis, and a sister died of glioblastoma at age 7. Another 7-year-old brother is so far clinically unaffected. The parents are consanguineous. Molecular diagnosis in the index patient revealed a constitutional homozygous mutation of the mismatch repair gene PMS2. The patient was in remission of his glioblastoma (WHO grade IV) after multimodal treatment followed by retinoic acid chemoprevention for 7 years. After discontinuation of retinoic acid medication, he developed a relapse of his brain tumour together with the simultaneous occurrence of three other different HNPCC-related carcinomas. We think that retinoic acid might have provided an effective chemoprevention in this patient with homozygous mismatch repair gene defect. We propose to take a retinoic acid chemoprevention into account in children with proven biallelic PMS2 mismatch repair mutations being at highest risk concerning the development of a malignancy.
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Acknowledgements
Sven Gottschling is Fellow in Paediatrics at University Childrens’ Hospital, University of Saarland, Germany. He wrote the manuscript and was involved in the patient’s treatment.
Harald Reinhard is Fellow in Paediatrics at University Childrens’ Hospital, University of Saarland, Germany. He was responsible for writing the manuscript and was involved in the patient’s treatment.
Constanze Pagenstecher is Fellow in the Institute of Human Genetics, University Hospital Bonn, Germany. She was responsible for gene sequenzing (mismatch repair genes MLH1 & MSH2) and participated in writing the manuscript.
Stefan Krüger is Fellow in the Department of Surgical Research and Institute of Clinical Genetics, Dresden University of Technology, Germany. He was responsible for gene sequenzing (PMS2) and participated in writing the manuscript.
Jochen Raedle is Fellow in the Department of Internal Medicine II, Division of Gastroenterology, University of Saarland, Germany. He was responsible for microsatellite analysis and treatment of the patient, and participated in writing the manuscript.
Guido Plotz is Fellow in the Department of Internal Medicine II, Division of Gastroenterology, University of Saarland, Germany. He was responsible for microsatellite analysis and participated in writing the manuscript.
Wolfram Henn is Head of the Division of Genetic Counselling at the Institute of Human Genetics, University of Saarland, Germany. He was responsible for genetic counselling and participated in writing the manuscript.
Reinhard Buettner is Head of the Institute of Pathology, University Hospital Bonn, Germany. He was responsible for immunohistochemistry and participated in writing the manuscript.
Sascha Meyer is Fellow in Paediatrics at University Childrens’ Hospital, University of Saarland, Germany. He participated in writing the manuscript and was involved in the patient’s treatment.
Norbert Graf is Head of the Department of Pediatric Hematology and Oncology at University Childrens’ Hospital, University of Saarland, Germany. He was responsible for writing the manuscript and was involved in the patient’s treatment.
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All contributing authors state that no conflict of interest is involved with this work.
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This work was supported by: German Cancer Aid, Project number: 70-3027-Ma-1 and 70-3032-Scha-4. Marianne and Klaus Paschke Award to J. Raedle.
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Gottschling, S., Reinhard, H., Pagenstecher, C. et al. Hypothesis: Possible role of retinoic acid therapy in patients with biallelic mismatch repair gene defects. Eur J Pediatr 167, 225–229 (2008). https://doi.org/10.1007/s00431-007-0474-3
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DOI: https://doi.org/10.1007/s00431-007-0474-3