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Cancer spectrum and frequency among children with Noonan, Costello, and cardio-facio-cutaneous syndromes.

ABSTRACT: Somatic mutations affecting components of the Ras-MAPK pathway are a common feature of cancer, whereas germline Ras pathway mutations cause developmental disorders including Noonan, Costello, and cardio-facio-cutaneous syndromes. These 'RASopathies' also represent cancer-prone syndromes, but the quantitative cancer risks remain unknown.We investigated the occurrence of childhood cancer including benign and malignant tumours of the central nervous system in a group of 735 individuals with germline mutations in Ras signalling pathway genes by matching their information with the German Childhood Cancer Registry.We observed 12 cases of cancer in the entire RASopathy cohort vs 1.12 expected (based on German population-based incidence rates). This corresponds to a 10.5-fold increased risk of all childhood cancers combined (standardised incidence ratio (SIR)=10.5, 95% confidence interval=5.4-18.3). The specific cancers included juvenile myelomonocytic leukaemia=4; brain tumour=3; acute lymphoblastic leukaemia=2; rhabdomyosarcoma=2; and neuroblastoma=1. The childhood cancer SIR in Noonan syndrome patients was 8.1, whereas that for Costello syndrome patients was 42.4.These data comprise the first quantitative evidence documenting that the germline mutations in Ras signalling pathway genes are associated with increased risks of both childhood leukaemia and solid tumours.

SUBMITTER: Kratz CP

PROVIDER: S-EPMC4402457 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Cancer spectrum and frequency among children with Noonan, Costello, and cardio-facio-cutaneous syndromes.

Kratz C P CP Franke L L Peters H H Kohlschmidt N N Kazmierczak B B Finckh U U Bier A A Eichhorn B B Blank C C Kraus C C Kohlhase J J Pauli S S Wildhardt G G Kutsche K K Auber B B Christmann A A Bachmann N N Mitter D D Cremer F W FW Mayer K K Daumer-Haas C C Nevinny-Stickel-Hinzpeter C C Oeffner F F Schlüter G G Gencik M M Überlacker B B Lissewski C C Schanze I I Greene M H MH Spix C C Zenker M M

British journal of cancer 20150305 8

<h4>Background</h4>Somatic mutations affecting components of the Ras-MAPK pathway are a common feature of cancer, whereas germline Ras pathway mutations cause developmental disorders including Noonan, Costello, and cardio-facio-cutaneous syndromes. These 'RASopathies' also represent cancer-prone syndromes, but the quantitative cancer risks remain unknown.<h4>Methods</h4>We investigated the occurrence of childhood cancer including benign and malignant tumours of the central nervous system in a gr ...[more]

PMID: 25742478

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Project description:Backgroundcardio-facio-cutaneous syndrome is a rare genetic disorder affecting less than 900 people in the world. It is mainly characterized by craniofacial, dermatologic and cardiac defects, but also gastroenterological symptoms may be present, ranging from feeding difficulties to gastroesophageal reflux and constipation.In this report we describe a case of this syndrome characterized by severe feeding and growth difficulties, with a particular focus on the management of gastroenterological complications.Case presentationthe patient was a caucasian male affected by Cardio-Facio-Cutaneous syndrome who presented feeding difficulties already a few hours after birth. These symptoms worsened in the following months and lead to a complete growth arrest and malnutrition. He was first treated with a nasogastric tube placement. Subsequently, a laparoscopic Nissen fundoplication and a laparoscopic Stamm gastrostomy were performed. The child was fed with nocturnal enteral nutrition and diurnal oral and enteral nutrition. Eventually the patient resumed feeding validly and regained adequate growth.Conclusionthis paper aims to bring to light a complex rare syndrome that infrequently comes to the attention of the pediatricians and whose diagnosis is not always straightforward. We also highlight the possible complications under a gastroenterologic point of view. Our contribution can be helpful to the pediatrician in the first diagnostic suspect of this syndrome. In particular, it is worth highlighting that -in an infant with Noonan-like features- symptoms like suction or swallowing problems, vomiting and feeding difficulties should orient towards the diagnosis of a Cardio-facio-cutaneous syndrome. It is also important to stress that its related gastroenterological issues may lead to severe growth failure and therefore the role of the gastroenterologist is key to manage supplemental feeding and to establish whether a nasogastric or gastrostomic tube placement is necessary.

Dataset Information

Cancer spectrum and frequency among children with Noonan, Costello, and cardio-facio-cutaneous syndromes.

Publications

Cancer spectrum and frequency among children with Noonan, Costello, and cardio-facio-cutaneous syndromes.

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