Bone marrow failure syndromes (BMFS) encompass a spectrum of acquired and constitutional disorders characterized by impaired hematopoiesis and cytopenias. In pediatric patients, constitutional BMFS represent up to 50% of cases, yet their diagnosis remains challenging due to subtle or absent extra-hematologic manifestations that mimic immune aplastic anemia. Accurate differentiation is essential, as it directly influences prognosis, therapeutic strategy, surveillance for extra-hematopoietic complications, and donor selection for hematopoietic cell transplantation. This review presents a structured diagnostic framework for pediatric BMFS, integrating clinical history, physical examination, bone marrow morphology, flow cytometry, cytogenetic analysis, disease-specific functional assays, and next-generation sequencing (NGS). Chromosomal breakage testing remains the gold-standard assay for Fanconi anemia, while telomere length measurement is the strongest predictor for differentiating constitutional from immune BMF. NGS enables comprehensive germline variant detection, resolves diagnostically ambiguous presentations, and informs genotype-guided familial screening. Recognition of disease-specific patterns of clonal hematopoiesis further refines diagnostic precision and risk stratification. A stepwise, evidence-based approach is essential to optimize early diagnosis and long-term outcomes in pediatric patients with BMFS.
Catto et al. (Mon,) studied this question.