Childhood cancer predisposition syndromes—A concise review and recommendations by the Cancer Predisposition Working Group of the Society for Pediatric Oncology and Hematology

Abstract

Heritable predisposition is an important cause of cancer in children and adolescents. Although a large number of cancer predisposition genes and their associated syndromes and malignancies have already been described, it appears likely that there are more pediatric cancer patients in whom heritable cancer predisposition syndromes have yet to be recognized. In a consensus meeting in the beginning of 2016, we convened experts in Human Genetics and Pediatric Hematology/Oncology to review the available data, to categorize the large amount of information, and to develop recommendations regarding when a cancer predisposition syndrome should be suspected in a young oncology patient. This review summarizes the current knowledge of cancer predisposition syndromes in pediatric oncology and provides essential information on clinical situations in which a childhood cancer predisposition syndrome should be suspected.

Genetic Counselor Recommendations for Cancer Predisposition Evaluation and Surveillance in the Pediatric Oncology Patient

“…Referral recommendations and tools for providers to recognize appropriate referrals are available. Positive family histories, high-genetic risk solid tumor types (see Table 1), multiple primary tumors, additional physical or clinical features, and treatment toxicity (15)(16)(17)(18) all should be factored into the referral process. In the future, however, genetic testing may be considered for all children with cancer given the limitations of current referral and genetic testing criteria.…”

Genetic predisposition in children with cancer – affected families' acceptance of Trio-WES

“…b Overview of cancer diagnoses in first-or seconddegree relatives. Same cancer entities were counted just once per family Cancer research (AACR) [11,12]. Examples of children in whom diagnosis of a CPS led to adaptation of cancer therapy and/or inclusion in a cancer surveillance program, respectively, are given in Table 5.…”

Seltene Tumordispositionssyndrome mit Manifestation im Kindesalter

“…Im Rahmen dieser Übersicht fokussieren wir auf konstitutionelle genetische Veränderungen der Gene ALK und PHOX2B [20,26]. Daneben spielen aber auch andere Syndrome eine Rolle, zum Beispiel RASopathien (insbesondere Costello-Syndrom), das Li-Fraumeni-Syndrom, das BWS mit Keimbahnmutationen im CDKN1C-Gen (siehe oben), das Sotos-Syndrom und das Weaver-Syndrom [4].…”

“…Darüber hinaus gibt es Berichte über Medulloblastom-Assoziatonen bei Patienten mit pathogenen Keimbahnmutationen in den Genen CREBBP und EP300 (Rubinstein-Taybi-Syndrom) sowie biallelen Mutationen im NBN-Gen (Nijmegen-Breakage-Syndrom), den MismatchReparaturgenen (konstitutionelle Mismatch-Reparatur-Defizienz) und dem BRCA2-und PALB2-Gen (Fanconi-Anämie) [4,33]. …”

“…Andere relevante Erkrankungen stehen nicht im Fokus dieses Artikels. Wir verweisen hier auf die weiteren Beiträge dieses Themenheftes und eine jüngst publizierte Übersicht der interdisziplinären Arbeitsgemeinschaft zur genetischen Krebsprädisposition der Gesellschaft für pädiatrische Onkologie und Hämatolo-gie [4].…”