Simultaneous Occurrence of Multiple Neoplasms in Children with Cancer Predisposition Syndromes: Collaborating with Abnormal Genes.

The identification of cancer predisposition syndromes (CPSs) plays a crucial role in understanding the etiology of pediatric cancers. CPSs are genetic mutations that increase the risk of developing cancer at an earlier age compared to the risk for the general population. This article aims to provide a comprehensive analysis of three unique cases involving pediatric patients with CPS who were diagnosed with multiple simultaneous or metachronous cancers. The first case involves a child with embryonal rhabdomyosarcoma, nephroblastoma, glioma, and subsequent medulloblastoma. Genetic analysis identified two pathogenic variants in the BRCA2 gene. The second case involves a child with alveolar rhabdomyosarcoma, juvenile xanthogranuloma, gliomas, and subsequent JMML/MDS/MPS. A pathogenic variant in the NF1 gene was identified. The third case involves a child with pleuropulmonary blastoma and pediatric cystic nephroma/nephroblastoma, in whom a pathogenic variant in the DICER1 gene was identified. Multiple simultaneous and metachronous cancers in pediatric patients with CPSs are a rare but significant phenomenon. Comprehensive analysis and genetic testing play significant roles in understanding the underlying mechanisms and guiding treatment strategies for these unique cases. Early detection and targeted interventions are important for improving outcomes in these individuals.

Why Is Health Care for Children with Down Syndrome So Crucial from the First Days of Life? A Retrospective Cohort Study Emphasized Transient Abnormal Myelopoiesis (TAM) Syndrome at Three Centers.

Down syndrome (DS) is a common genetic disorder and is associated with an increased likelihood of many diseases, including defects of the heart, genitourinary system, gastrointestinal tract, and oncological diseases. The aim of this study was to analyze medical problems occurring in newborns with DS and to create a basic diagnostic and therapeutic algorithm intended primarily for neonatologists, pediatricians, family physicians, and physicians of other specialties caring for children with DS. Over a 5-year period, the medical records of 161 neonates with Down syndrome from four neonatology departments in Poznan, Poland, were examined. After applying exclusion criteria, 111 patients were analyzed. Data obtained from medical history included sex, week of gestation, birth weight, APGAR score, clinical symptoms, peripheral blood count with smear, and clinical features such as jaundice, hemorrhagic diathesis, ascites, hepato- or splenomegaly, pericardial or pleural effusion, respiratory failure, and other rare transient signs of abnormal myelopoiesis: fetal edema, hepatic fibrosis, renal failure, and rush. In the study group, 8% of children with Down syndrome were diagnosed with a heart and 1.8% with a genitourinary defect. Transient abnormal myelopoiesis syndrome (Transient abnormal myelopoiesis (TAM)) was found in 10% of newborns with DS. A blood count with blood smear, cardiology consultation with echocardiography, and an abdominal ultrasound should be performed in the first few days after birth in all newborns with Down syndrome. If this is not possible and the child's condition is stable, these tests can be performed within 2-3 months after birth.

Clinical, Histological, Cytogenetic and Molecular Analysis of Monozygous Twins with Wilms Tumor.

The familial occurrence of childhood cancers has been proven for a long time. Wilms' tumors often do not have a clear germline genetic cause. However, approximately 2% of all nephroblastoma cases are familial. Descriptions of twins with the same cancer are extremely rare, so our aim was to present the background of the available literature of the occurrence of Wilms' tumor in a pair of monozygotic twin girls with detailed clinical, histological, and molecular analysis. Two twins were born of unrelated Caucasian parents. Family history revealed no known chronic diseases or malformations. At the age of 3.5 years, the first twin was admitted to the emergency department due to hematuria and abdominal pain. Ultrasound examination revealed an enlarged right kidney, 12.8 cm, with a mass in the upper pole measuring 56 × 69 × 78 mm. The second girl was referred for an abdominal ultrasound, which revealed a right kidney measuring 8.6 cm with a central mass measuring 54 × 45 × 41 mm. Both children underwent surgical resection, and the histopathological result showed a mixed form of nephroblastoma, predominantly epithelioid with residual blastemal compartment. Detailed clinical, histological, cytogenetic, and molecular analyses were performed on both sisters. It was also decided to identify environmental factors. Information was obtained that the girls' parents run a farm and regularly use pesticides and chemical rodenticides. Based on our observations and the available literature, Wilms tumor in monozygotic twins may be present. Both genetic and environmental factors may be involved in the development of tumors. After excluding methylation abnormalities and mutations in the genes studied, we questioned whether the onset of Wilms tumor in both sisters could be the result of exposure of the twins' parents to pesticides.

A Case report: Co-occurrence of IMAGe syndrome and Rhabdomyosarcoma.

IMAGe syndrome is a rare congenital disorder, presenting with intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita and genital anomalies (in males). So far only 17 individuals have been diagnosed molecularly with IMAGe syndrome, this patient is the first case of an individual diagnosed with IMAGe and concurrent rhabdomyosarcoma. The patient was born at 30 weeks' gestation and received treatment for hyponatremia and hyperkalemia. At 4 9/12 years of age the patient showed a painless, non-mobile mass on the left thigh. In the biopsy performed a sarcoma weave with solid, nest-like growth, with characteristics of rhabdomyosarcoma was identified. The family history and physical examination indicated IMAGe syndrome so genetic testing was requested. A whole exome sequencing procedure with use of SureSelectXT Human ALL Exon V7, confirmed a single nucleotide variant NM_000076.2(CDKN1C):c.820G>A (p.Asp274Asn); identifying a missense mutation in the imprinted gene CDKN1C associated with IMAGe syndrome. Although tumours associated with CDKN1C are rare, deregulation of imprinted genes is increasingly being recognised as a mechanism of tumorigenesis in cancer; chromosomal region 11p15.5 contains a cluster of imprinted genes. This same region is the most consistent site of allele loss in rhabdomyosarcoma and is the same region altered in both IMAGe and Beckwith-Wiedemann syndrome. Molecular studies have found genetic changes in the 11p15 region in a variety of embryonal tumours like Wilms tumours which are commonly developed in Beckwith-Wiedemann syndrome and embryonal rhabdomyosarcoma. Through this case we aim to present the possibility of oncogenesis in patients with IMAGe syndrome, specifically rhabdomyosarcoma.