Molecular Investigation of Children With Suspected Bone Marrow Failure Syndromes at a Pediatric Referral Center Within the Brazilian Unified Health System: Results of an Interdisciplinary Approach
Year: 2026
Type: article
Study design: Observational Study
Abstract: Introduction Bone marrow failure syndromes are rare, heterogeneous disorders whose clinical and genetic variability complicates diagnosis, requiring the integration of specialized care, translational research, and molecular investigation. Objective To describe the results of implementing an interdisciplinary workflow for the investigation of children with suspected bone marrow failure syndromes, based on the principles of translational research. Materials and Methods This descriptive study was conducted between 2023 and 2026 at a tertiary public pediatric hospital in the Federal District, Brazil. Patients with suspected bone marrow failure syndromes were referred for molecular investigation within the framework of an institutional research project. After written informed consent was obtained, clinical and laboratory data were collected by the multidisciplinary team and managed by the research nursing team using the Research Electronic Data Capture (REDCap) platform. Biological samples underwent next-generation sequencing (NGS) at the Translational Research Laboratory. The results were discussed in 36 interdisciplinary meetings involving hematologists, biologists, pharmacists, bioinformaticians, and research nurses to establish clinicomolecular correlations and support clinical decision-making. Results A total of 119 patients were enrolled, with a slight predominance of males (54.6%; n=65) and a mean age of 7.1±5.4 years. The main reasons for referral were unexplained persistent cytopenia (43.7%; n=52), bone marrow failure syndrome (32.8%; n=39), and early-onset autoimmunity or lymphoproliferation (20.2%; n=24). At the time of this analysis, 77 molecular reports had been completed, and molecular investigation identified phenotype-related variants in 38% (n=29) of patients, while incidental variants were detected in 11.7% (n=9). Among cases with phenotype-related findings, 34 diagnostic or candidate variants were identified. According to the American College of Medical Genetics and Genomics (ACMG) criteria, 59% (n=20) of the variants were classified as pathogenic, 21% (n=7) as likely pathogenic, and 21% (n=7) as variants of uncertain significance (VUS). The latter showed high concordance with the clinical phenotype and were considered by the investigators to be potential diagnostic candidate variants. Single-nucleotide variants (SNVs) predominated (88%; n=30), mainly missense variants, affecting genes associated with inherited thrombocytopenias, Fanconi anemia, Diamond-Blackfan anemia, congenital neutropenias, and immune dysregulation. Discussion Systematic interdisciplinary case discussions enabled a contextualized interpretation of molecular findings, particularly variants of uncertain significance, increasing their clinical relevance and contributing to individualized diagnostic and therapeutic decisions. Molecular investigation established the molecular diagnosis in 38% of patients, highlighting the value of interdisciplinary collaboration in elucidating complex cases. Conclusion The interdisciplinary workflow based on translational research integrated specialized care, molecular investigation, and clinical decision-making, facilitating diagnostic clarification, strengthening clinicomolecular correlation, and improving the care of children with rare hematological disorders within the Brazilian Unified Health System (SUS).
Institution: Universidade de Brasília
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7223112542