Validation of a clinical screening instrument for tumour predisposition syndromes in patients with childhood cancer (TuPS): protocol for a prospective, observational, multicentre study.

Introduction: Recognising a tumour predisposition syndrome (TPS) in patients with childhood cancer is of significant clinical relevance, as it affects treatment, prognosis and facilitates genetic counselling. Previous studies revealed that only half of the known TPSs are recognised during standard paediatric cancer care. In current medical practice it is impossible to refer every patient with childhood cancer to a clinical geneticist, due to limited capacity for routine genetic consultation.

3D morphometry aids facial analysis of individuals with a childhood cancer.

A group of patients who had cancer as a child were previously found to have distinct patterns of morphological abnormalities. In this study, we investigated the added value of 3D shape analysis to characterize their facial morphology. Primarily, we showed in an objective and quantitative manner that the overall facial dysmorphism of the individuals who had had a childhood cancer was significantly greater than that of the controls.

High-sensitivity sequencing reveals multi-organ somatic mosaicism causing DICER1 syndrome.

Background: Somatic mosaicism is being increasingly recognised as an important cause of non-Mendelian presentations of hereditary syndromes. A previous whole-exome sequencing study using DNA derived from peripheral blood identified mosaic mutations in DICER1 in two children with overgrowth and developmental delay as well as more typical phenotypes of germline DICER1 mutation. However, very-low-frequency mosaicism is difficult to detect, and thus, causal mutations can go unnoticed.

Co-occurrence in body site of malformations and cancer.

In many malformation syndromes benign and malignant tumours develop more frequently than in the general population. Malformations result from an abnormal intrinsic developmental process. It can be hypothesised that disturbed regulation of cell growth as can become evident by the presence of benign and malignant tumours, which will occur at the same site of a malformation or at other sites at which the gene involved in the malformation is functioning.

Brain tumors and syndromes in children.

(Brain) tumors are usually a disorder of aged individuals. If a brain tumor occurs in a child, there is a possible genetic susceptibility for this. Such genetic susceptibilities often show other signs and symptoms.

Face shape differs in phylogenetically related populations.

3D analysis of facial morphology has delineated facial phenotypes in many medical conditions and detected fine grained differences between typical and atypical patients to inform genotype-phenotype studies. Next-generation sequencing techniques have enabled extremely detailed genotype-phenotype correlative analysis. Such comparisons typically employ control groups matched for age, sex and ethnicity and the distinction between ethnic categories in genotype-phenotype studies has been widely debated.

The development of a clinical screening instrument for tumour predisposition syndromes in childhood cancer patients.

Background: Identification of tumour predisposition syndromes in patients who have cancer in childhood is paramount for optimal care. A screening instrument that can help to identify such patients will facilitate physicians caring for children with cancer. The complete screening instrument should consist of a standardised series of pictures and a screening form for manifestations not visible in the pictures.

PTEN hamartoma tumor syndrome and Gorham-Stout phenomenon.

PTEN: hamartoma tumor syndrome (PHTS) is a group of syndromes caused by mutations in PTEN. Gorham-Stout phenomenon (GSP) is a rare condition characterized by proliferation of vascular structures in bones, resulting in progressive osteolysis. Here we present a 1-year-old boy with PHTS and GSP.

Differentiated thyroid carcinoma after 131I-MIBG treatment for neuroblastoma during childhood: description of the first two cases.

Background: It is well known that the thyroid gland is sensitive to the damaging effects of irradiation (X-radiation or (131)I¯). For this reason, during exposure to (131)I- metaiodobenzylguanidine (MIBG) in children with neuroblastoma (NBL), the thyroid gland is protected against radiation damage by the administration of either potassium iodide (KI) or a combination of KI, thyroxine, and methimazole. Although hypothyroidism and benign thyroid nodules are frequently encountered during follow-up of these children, differentiated thyroid carcinoma (DTC) has never been reported after treatment with (131)I-MIBG in children who have not been given external beam irradiation.