Consequences of diagnosing a tumor predisposition syndrome in children with cancer: A literature review

Up to 8.5% of children with cancer have a genetic cause for their cancer: a tumor predisposition syndrome (TPS). Diagnosing a TPS is of great importance, as it may have major consequences for clinical care. Patients with TPSs require specific monitoring and management. We present an overview of the cancer-related and noncancer-related consequences for the 36 most common TPSs

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 phylogenetic tree based on genetic polymorphism studies divides the world population into nine subpopulations. Here we show statistically significant face shape differences between two European Caucasian populations of close phylogenetic and geographic proximity from the UK and The Netherlands. The average face shape differences between the Dutch and UK cohorts were visualised in dynamic morphs and signature heat maps, and quantified for their statistical significance using both conventional anthropometry and state of the art dense surface modelling techniques. Our results demonstrate significant differences between Dutch and UK face shape. Other studies have shown that genetic variants influence normal facial variation. Thus, face shape difference between populations could reflect underlying genetic difference. This should be taken into account in genotype-phenotype studies and we recommend that in those studies reference groups be established in the same population as the individuals who form the subject of the stud

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. We also demonstrated how the same approach can be used to detect a similar disparity for a more localized malar region comprising customized disconnected patches defined on both sides of the face. In addition, by comparing original face surfaces to their mirrored forms, we confirmed that the patient group had significantly greater facial asymmetry than the controls. Each of these results made use of surface shape differences not detectable by simple linear or angular characteristics as might be used in analyses based on measures captured manually or derived from landmarks annotating 2D photographic images. We conclude that 3D morphometric analysis of a relatively small heterogeneous patient group can further delineate face shape differences from typically developing individuals that are too subtle or geometrically complex to identify or quantify objectively with conventional clinical and anthropometric approaches. © 2016 Wiley Periodicals, Inc

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. We also demonstrated how the same approach can be used to detect a similar disparity for a more localized malar region comprising customized disconnected patches defined on both sides of the face. In addition, by comparing original face surfaces to their mirrored forms, we confirmed that the patient group had significantly greater facial asymmetry than the controls. Each of these results made use of surface shape differences not detectable by simple linear or angular characteristics as might be used in analyses based on measures captured manually or derived from landmarks annotating 2D photographic images. We conclude that 3D morphometric analysis of a relatively small heterogeneous patient group can further delineate face shape differences from typically developing individuals that are too subtle or geometrically complex to identify or quantify objectively with conventional clinical and anthropometric approaches. © 2016 Wiley Periodicals, Inc

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. Therefore, every child with a brain tumor should be carefully evaluated for the presence of a "tumor predisposition syndrome." Here, we provide an overview of the various central nervous system tumors that occur in children with syndromes and of the various syndromes that occur in children with brain tumor. Our aim is to facilitate recognition of syndromes in children with a brain tumor and early diagnosis of brain tumors in children with syndromes. Diagnosing tumor predisposition syndromes in children may have important consequences for prognosis, treatment, and screening for subsequent malignancies and nontumor manifestations. We discuss pitfalls in clinical and molecular diagnoses, and the consequences of diagnosing a hereditary disorder for family members. Our improved knowledge of cancer etiology is increasingly translated into management strategies in syndromes in general and will likely lead in the near future to personalized therapeutic approaches for tumor predisposition syndrome

Multiple tumors due to mosaic genome-wide paternal uniparental disomy

Mosaic genome-wide paternal uniparental disomy is an infrequently described disorder in which affected individuals have signs and symptoms that may resemble Beckwith-Wiedemann syndrome. In addition, they can develop multiple benign and malignant tumors throughout life. Routine molecular diagnostics may not detect the (characteristic) low level of mosaicism, and the diagnosis is likely to be missed. Genetic counseling and a life-long alertness for the development of tumors is indicated. We describe the long diagnostic process of a patient who already had a tumor at birth and developed multiple tumors in childhood and adulthood. Furthermore, we offer clues to recognize the entity

Differentiated Thyroid Carcinoma After I-131-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 I-131(-)). For this reason, during exposure to I-131-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 I-131-MIBG in children who have not been given external beam irradiation. Here, we describe the first two cases of DTC after I-131-MIBG-therapy. Patient Findings: A 6-year-old boy, treated with I-131-MIBG for NBL at the age of 4 months, and a 13-year-old girl, treated at the age of 9 months, were both diagnosed with DTC at 5 and 12 years after I-131-MIBG treatment, respectively. Both children received thyroid protection during exposure to I-131-MIBG. In each child DTC was discovered in nonpalpable nodules by thyroid ultrasound. Summary: The first two pediatric patients with DTC after treatment with I-131-MIBG are reported. Conclusions: Both these cases of DTC after I-131-MIBG for childhood NBL underline the importance of adequate thyroid protection against radiation exposure during treatment for NBL. Children who have been treated with I-131-MIBG should be given life-long follow-up, not only with regard to thyroid function, but also with surveillance for the development of thyroid nodules and thyroid cance

Muscle fiber dysfunction contributes to weakness in inclusion body myositis

Atrophy and fatty infiltration are important causes of muscle weakness in inclusion body myositis (IBM). Muscle weakness can also be caused by reduced specific force; i.e. the amount of force generated per unit of residual muscle tissue. This study investigates in vivo specific force of the quadriceps and ex vivo specific force of single muscle fibers in patients with IBM. We included 8 participants with IBM and 12 healthy controls, who all underwent quantitative muscle testing, quantitative MRI of the quadriceps and paired muscle biopsies of the quadriceps and tibialis anterior. Single muscle fibers were isolated to measure muscle fiber specific force and contractile properties. Both in vivo quadriceps specific force and ex vivo muscle fiber specific force were reduced. Muscle fiber dysfunction was accompanied by reduced active stiffness, which reflects a decrease in the number of attached actin-myosin cross-bridges during activation. Myosin concentration was reduced in IBM fibers. Because reduced specific force contributes to muscle weakness in patients with IBM, therapeutic strategies that augment muscle fiber strength may provide benefit to patients with IBM

საქართველოს სოციალისტური საბჭოთა რესპუბლიკის მუშათა და გლეხთა მთავრობის კანონთა და განკარგულებათა კრებული N16

Introduction: Recognising a tumour predisposition syndrome (TPS) in childhood cancer patients is of major clinical relevance. The presence of a TPS may be suggested by the type of tumour in the child. We present an overview of 23 childhood tumours that in themselves should be a reason to refer a child for genetic consultation. Methods: We performed a PubMed search to review the incidence of TPSs in children for 85 tumour types listed in the International Classification of Childhood Cancer third edition (ICCC-3). The results were discussed during a national consensus meeting with representative clinical geneticists from all six academic paediatric oncology centres in The Netherlands. A TPS incidence of 5% or more was considered a high probability and therefore in itself a reason for referral to a clinical geneticist. Results: The literature search resulted in data on the incidence of a TPS in 26 tumours. For 23/26 tumour types, a TPS incidence of 5% or higher was reported. In addition, during the consensus meeting the experts agreed that children with any carcinoma should always be referred for clinical genetic consultation as well, as it may point to a TPS. Conclusion: We present an overview of 23 paediatric tumours with a high probability of a TPS; this will facilitate paediatric oncologists to decide which patients should be referred for genetic consultation merely based on type of tumour. (C) 2017 Elsevier Ltd. All rights reserved