Cancer predisposition in children: genetics, phenotypes & screening

This thesis describes the genetic, phenotypic and screening aspects of tumor predisposition syndromes in childhood cancer patients. In tumor predisposition syndromes, the same constitutional molecular defects that lead to the clinical phenotype predispose the patient to develop specific cancers.
Structural genome variations were detected in childhood cancer patients showing one of the patterns of co-occurring morphological abnormalities as defined previously by Merks et al., which were hypothesized to be susceptibility loci.
3D Shape analysis was used in this same patient cohort, which demonstrated that the childhood cancer patients showed more overall facial dysmorphism, more dysmorphism in the malar region and increased facial asymmetry compared to controls. This showed the added value of morphometric analysis to further delineate face shape differences that are too subtle or geometrically complex to identify or quantify objectively with conventional clinical and anthropometric approaches.
3D photography was also used to demonstrate statistically significant differences in face shape between individuals from the UK and the Netherlands, two European Caucasian populations of close phylogenetic and geographic proximity. From these results we recommend, that in genotype-phenotype correlation studies reference groups should be established in the same population as the individuals who form the subject of the study.
Lastly, a screening instrument consisting of a screening form and 2D/3D picture series was developed, which showed to identify patients who (might) have a tumor predisposition syndrome in a first validation.