Update on cancer screening in children with syndromes of bone lesions, hereditary leiomyoma and renal cell carcinoma syndrome, and other rare syndromes.

The management of children with syndromes associated with an increased risk of benign and malignant neoplasms is a complex challenge for healthcare professionals. The 2023 AACR Childhood Cancer Predisposition Workshop provided updated consensus guidelines on cancer surveillance in these syndromes, aiming to improve early detection, intervention, and reduce morbidity associated with such neoplasms. In this paper, we review several of the rare conditions discussed in this workshop.

Update on Pediatric Surveillance Recommendations for PTEN Hamartoma Tumor Syndrome, DICER1-Related Tumor Predisposition, and Tuberous Sclerosis Complex.

PTEN hamartoma tumor syndrome (PHTS), DICER1-related tumor predisposition (DICER1) and tuberous sclerosis complex (TSC) are rare conditions which each increase risk for distinct spectra of benign and malignant neoplasms throughout childhood and adulthood. Surveillance considerations for each of these conditions focus on patient and family education, early detection and multidisciplinary care. In this manuscript, we present updated surveillance recommendations and considerations for children and adolescents with PHTS, DICER1 and TSC and provide suggestions for further research in each of these conditions.

Late-onset tumors in rhabdoid tumor predisposition syndrome type-1 (RTPS1) and implications for surveillance.

Rhabdoid tumor predisposition syndrome type-1 (RTPS1) is characterized by germline pathogenic variants in SMARCB1 and development of INI1-deficient rhabdoid tumors in early childhood. Due to its poor prognosis, the risk of subsequent tumor development and the impact of surveillance at later ages are poorly understood. We retrospectively reviewed individuals referred to the Cancer Genetics Program at The Hospital for Sick Children for SMARCB1 genetic testing and/or surveillance for RTPS1.

Update on Genetic Counselor Practice and Recommendations for Pediatric Cancer Predisposition Evaluation and Surveillance.

In July 2023, the American Association for Cancer Research held the second Childhood Cancer Predisposition Workshop, at which international experts in pediatric cancer predisposition met to update the previously published 2017 consensus statements on pediatric cancer predisposition syndromes. Since 2017, advances in tumor and germline genetic testing and increased understanding of cancer predisposition in patients with pediatric cancer have led to significant changes in clinical care. Here, we provide an updated genetic counseling framework for pediatric oncology professionals.

Exome sequencing identifies PD-L2 as a potential predisposition gene for lymphoma.

To investigate germline predisposition in lymphoma, we performed whole-exome sequencing and discovered a novel variant (c.817-1G>T) in programmed cell death 1 ligand 2 (PD-L2) in a family with early-onset lymphomas and other cancers. The variant was present in the proband with follicular lymphoma and his son with Hodgkin's lymphoma.

Perspectives and Experiences of Parents and Adolescents Who Participate in a Pediatric Precision Oncology Program: "When You Feel Helpless, This Kind of Thing Is Very Helpful".

Purpose: The SickKids Cancer Sequencing (KiCS) Program, launched in 2016, evaluates the clinical utility of paired tumor/germline Next-Generation Sequencing (NGS) in pediatric oncology patients with hard-to-cure and rare cancers. In anticipation of further widespread adoption of NGS, we aimed to characterize the experiences and perspectives of adolescents and parents of patients who have already undergone NGS evaluation, focusing on the psychosocial impact and personal utility.

Methods: Parents of patients with pediatric cancer and adolescent patients who have participated in KiCS were invited to participate in semistructured interviews.

Survival Benefit for Individuals With Constitutional Mismatch Repair Deficiency Undergoing Surveillance.

Purpose: Constitutional mismatch repair deficiency syndrome (CMMRD) is a lethal cancer predisposition syndrome characterized by early-onset synchronous and metachronous multiorgan tumors. We designed a surveillance protocol for early tumor detection in these individuals.

Patients And Methods: Data were collected from patients with confirmed CMMRD who were registered in the International Replication Repair Deficiency Consortium.

Tumor surveillance for children and adolescents with cancer predisposition syndromes: The psychosocial impact reported by adolescents and caregivers.

Purpose: Individuals with cancer predisposition syndromes (CPS) are often followed in cancer screening programs, which aim to detect early stage tumors. While cancer surveillance has the potential to improve patient outcomes, its psychosocial impact is uncharacterized in the pediatric population. We examined the cancer surveillance experience from the perspectives of adolescents and parents of children at risk of developing cancer.

Non-rhabdomyosarcoma soft tissue sarcomas diagnosed in patients at a young age. An overview of clinical, pathological, and molecular findings.

Objective: Disease spectrum in pediatric sarcoma differs substantially from adults. We report a cohort of very young children with non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) detailing their molecular features, treatment, and outcome.

Methods: We report features of consecutive children (age <2 years) with NRSTS (2000-2017).

Comprehensive characterization of a Canadian cohort of von Hippel-Lindau disease patients.

Von Hippel-Lindau disease (VHL) is a heritable condition caused by pathogenic variants in VHL and is characterized by benign and malignant lesions in the central nervous system (CNS) and abdominal viscera. Due to its variable expressivity, existing efforts to collate VHL patient data do not adequately capture all VHL manifestations. We developed a comprehensive and standardized VHL database in the web-based application, REDCap, that thoroughly captures all VHL manifestation data.

Evidence for genetic anticipation in vonHippel-Lindau syndrome.

Background: von Hippel-Lindau (vHL) syndrome is a rare autosomal-dominant disorder that confers a lifelong risk for developing both benign and malignant tumours in multiple organs. Recent evidence suggests that vHL may exhibit genetic anticipation (GA). The aim of this study was to determine if GA occurs in vHL, and if telomere shortening may be a factor in GA.

DICER1 syndrome: Approach to testing and management at a large pediatric tertiary care center.

Background: To expand the current knowledge of DICER1 syndrome and to propose criteria for genetic testing based on experience at a pediatric tertiary care center.

Procedure: This study involved a retrospective chart review of the 78 patients (47 probands and 31 family members) seen in the Cancer Genetics Program at The Hospital for Sick Children (SickKids) who were offered genetic testing for DICER1.

Results: Of 47 probands offered genetic testing for DICER1, 46 pursued testing: 11 (23.

Pediatric imaging in DICER1 syndrome.

Background: DICER1 syndrome, arising from a mutation in the DICER1 gene mapped to chromosome 14q32, is associated with an increased risk of a range of benign and malignant neoplasms.

Objective: To determine the spectrum of abnormalities and imaging characteristics in patients with DICER1 syndrome at a tertiary pediatric hospital.

Materials And Methods: This retrospective analysis evaluated imaging in patients ≤18 years with DICER1 germline variants between January 2004 and July 2016.

Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: 11 year follow-up of a prospective observational study.

Background: Carriers of a germline TP53 pathogenic variant have a substantial lifetime risk of developing cancer. In 2011, we did a prospective observational study of members of families who chose to either undergo a comprehensive surveillance protocol for individuals with Li-Fraumeni syndrome or not. We sought to update our assessment of and modify the surveillance protocol, so in this study we report both longer follow-up of these patients and additional patients who underwent surveillance, as well as update the originally presented surveillance protocol.

PhenomeCentral: a portal for phenotypic and genotypic matchmaking of patients with rare genetic diseases.

The discovery of disease-causing mutations typically requires confirmation of the variant or gene in multiple unrelated individuals, and a large number of rare genetic diseases remain unsolved due to difficulty identifying second families. To enable the secure sharing of case records by clinicians and rare disease scientists, we have developed the PhenomeCentral portal (https://phenomecentral.org).