How harmful is genetic testing for familial adenomatous polyposis (FAP) in young children; the parents' experience

Predictive genetic testing for familial adenomatous polyposis (FAP) is routinely offered to children at-risk from the age of 10 years onwards. Predictive testing for FAP at a younger age is debatable, because of absence of medical benefits. However, circumstances may arise when testing at a younger age (< 10 years) is appropriate. Currently, there is a lack of published experience with predictive testing of children at this young age. We evaluated 13 children who were tested for FAP at the age younger than 10 years; 7 mutation-carriers and 6 non-carriers. Parents of these children were re-contacted and open-ended semi-structured interviewed. None of the contacted parents regretted the timing of genetic testing. The major reasons for testing at the young age were (1) testing of all children in the family at the same moment; (2) certainty for the future; and (3) preparing the child for future surveillance. None of the parents observed changes in mental or physical health in their child after testing. Also, young genetic testing did not lead to colon surveillance before it was indicated. Genetic testing for FAP at a young age is experienced as causing no harm by parents. Future studies should evaluate children's own experiences with early genetic testing

Identification of Familial Adenomatous Polyposis carriers among children with desmoid tumours

Objective: Desmoid tumours are rare mesenchymal tumours with unpredictable progression and high recurrence risk. They can occur sporadically or in association with Familial Adenomatous Polyposis (FAP), which is caused by germline APC mutations. The Wnt/beta-catenin pathway has a central role in the pathogenesis of desmoid tumours. These tumours can occur due to either a somatic CTNNB1 or APC mutation but can also be the first manifestation of FAP. Because germline APC analysis is not routinely performed in children with desmoid tumours, the diagnosis FAP may escape detection. The aim of this study is to form guidelines for the identification of possible APC germline mutation carriers among children with desmoid tumours, based on CTNNB1 mutation analysis and immunohistochemical analysis (IHC) for beta-catenin. Patients and methods: We performed IHC of beta-catenin and mutation analysis of CTNNB1 and APC in 18 paediatric desmoid tumours, diagnosed between 1990 and 2009 in the Erasmus MC, Rotterdam. Results: In 11 tumours, IHC showed an abnormal nuclear beta-catenin accumulation. In this group a CTNNB1 mutation was detected in seven tumours. In two tumours with an abnormal nuclear beta-catenin accumulation and no CTNNB1 mutation, an APC mutation was identified, which appeared to be a germline mutation. Conclusions: Aberrant staining of beta-catenin in paediatric desmoids helps to identify children at risk for FAP. We recommend to screen paediatric desmoid tumours for nuclear localisation of beta-catenin and consequently for CTNNB1 mutations. For patients with nuclear beta-catenin expression and no CTNNB1 mutations, APC mutation analysis should be offered after genetic counselling. (C) 2012 Elsevier Ltd. All rights reserved