Diagnostic criteria for constitutional mismatch repair deficiency syndrome: suggestions of the European consortium ‘Care for CMMRD’ (C4CMMRD)
Year: 2014
Type: review
Abstract: Constitutional mismatch repair deficiency (CMMRD) syndrome is a distinct childhood cancer predisposition syndrome that results from biallelic germline mutations in one of the four MMR genes, MLH1, MSH2, MSH6 or PMS2. The tumour spectrum is very broad, including mainly haematological, brain and intestinal tract tumours. Patients show a variety of non-malignant features that are indicative of CMMRD. However, currently no criteria that should entail diagnostic evaluation of CMMRD exist. We present a three-point scoring system for the suspected diagnosis CMMRD in a paediatric/young adult cancer patient. Tumours highly specific for CMMRD syndrome are assigned three points, malignancies overrepresented in CMMRD two points and all other malignancies one point. According to their specificity for CMMRD and their frequency in the general population, additional features are weighted with 1-2 points. They include multiple hyperpigmented and hypopigmented skin areas, brain malformations, pilomatricomas, a second childhood malignancy, a Lynch syndrome (LS)-associated tumour in a relative and parental consanguinity. According to the scoring system, CMMRD should be suspected in any cancer patient who reaches a minimum of three points by adding the points of the malignancy and the additional features. The diagnostic steps to confirm or refute the suspected diagnosis are outlined. We expect that application of the suggested strategy for CMMRD diagnosis will increase the number of patients being identified at the time when they develop their first tumour. This will allow adjustment of the treatment modalities, offering surveillance strategies for second malignancies and appropriate counselling of the entire family.
Source: Journal of Medical Genetics
Institutions: Innsbruck Medical University, Universität Innsbruck, Medizinische Hochschule Hannover, Leiden University Medical Center, Institut Gustave Roussy, Inserm, Sorbonne Université, Assistance Publique – Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Centre de Recherche Saint-Antoine, Université Pierre-et-Marie-Curie, Hôpital d'Hautepierre, Copenhagen University Hospital, Rigshospitalet, Hadassah Medical Center, University Hospital Bratislava, Comenius University Bratislava, Centre for Biomedical Network Research on Rare Diseases, Fundación Pública Galega de Medicina Xenómica, Instituto de Investigación Sanitaria de Santiago, Servicio Gallego de Salud, Medical University of Vienna, University of Münster, University Hospital Münster
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2098897153