1. Agenesis of the corpus callosum and gray matter heterotopia in three patients with constitutional mismatch repair deficiency syndrome
- Author
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Mieke M. van Haelst, Rutger A.J. Nievelstein, Stephen P. Robertson, Milan Rimac, Danielle Bodmer, Michael T. Gabbett, Minna Nyström, Annekatrin Wernstedt, Johan Offerhaus, Birgit Krabichler, Johannes Zschocke, Martine Raphael, Katharina Wimmer, Minttu Kansikas, Wayne Nicholls, Ulrich Strasser, Annette F. Baas, Pediatric surgery, Human genetics, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Reproduction & Development (AR&D), Pathology, and Other departments
- Subjects
Male ,Gray matter heterotopia ,Pediatrics ,Contractile Proteins ,0302 clinical medicine ,Pregnancy ,PMS2 ,Child ,Agenesis of the corpus callosum ,Genetics (clinical) ,Mismatch Repair Endonuclease PMS2 ,Adenosine Triphosphatases ,0303 health sciences ,education.field_of_study ,Microfilament Proteins ,Nuclear Proteins ,Syndrome ,Parotid Neoplasms ,3. Good health ,DNA-Binding Proteins ,Heterotopia (medicine) ,Child, Preschool ,030220 oncology & carcinogenesis ,Female ,Microsatellite Instability ,MutL Protein Homolog 1 ,medicine.medical_specialty ,Filamins ,Population ,Biology ,Article ,03 medical and health sciences ,Internal medicine ,Genetics ,medicine ,Humans ,education ,Adaptor Proteins, Signal Transducing ,030304 developmental biology ,constitutional mismatch repair deficiency syndrome ,agenesis of corpus callosum ,gray matter heterotopia ,biallelic germline mutation ,childhood cancer ,medicine.disease ,DNA Repair-Deficiency Disorders ,Pediatric cancer ,MSH6 ,DNA Repair Enzymes ,Endocrinology ,MSH2 ,Mutation ,Agenesis of Corpus Callosum ,Glioblastoma ,Malformations of Cortical Development, Group II - Abstract
Constitutional mismatch repair deficiency (CMMR-D) syndrome is a rare inherited childhood cancer predisposition caused by biallelic germline mutations in one of the four mismatch repair (MMR)-genes, MLH1, MSH2, MSH6 or PMS2. Owing to a wide tumor spectrum, the lack of specific clinical features and the overlap with other cancer predisposing syndromes, diagnosis of CMMR-D is often delayed in pediatric cancer patients. Here, we report of three new CMMR-D patients all of whom developed more than one malignancy. The common finding in these three patients is agenesis of the corpus callosum (ACC). Gray matter heterotopia is present in two patients. One of the 57 previously reported CMMR-D patients with brain tumors (therefore all likely had cerebral imaging) also had ACC. With the present report the prevalence of cerebral malformations is at least 4/60 (6.6%). This number is well above the population birth prevalence of 0.09-0.36 live births with these cerebral malformations, suggesting that ACC and heterotopia are features of CMMR-D. Therefore, the presence of cerebral malformations in pediatric cancer patients should alert to the possible diagnosis of CMMR-D. ACC and gray matter heterotopia are the first congenital malformations described to occur at higher frequency in CMMR-D patients than in the general population. Further systematic evaluations of CMMR-D patients are needed to identify possible other malformations associated with this syndrome. European Journal of Human Genetics (2013) 21, 55-61; doi: 10.1038/ejhg.2012.117; published online 13 June 2012
- Published
- 2013