Pediatric Myelodysplastic Syndrome: Causes, Risk Factors, and Underlying Mechanisms

Myelodysplastic syndrome (MDS) in children is a rare and complex group of disorders characterized by dysfunctional blood cell production in the bone marrow. At its core, pediatric MDS arises when hematopoietic stem cells or progenitor cells—responsible for generating red blood cells, white blood cells, and platelets—become damaged or impaired. This disruption leads to ineffective hematopoiesis, meaning the body fails to produce sufficient numbers of healthy, mature blood cells.

Understanding the Clinical Presentation

Children affected by this condition often present with persistent anemia, which may manifest as fatigue, pallor, and shortness of breath. In addition to low red blood cell counts, many patients also experience neutropenia (low white blood cells) and thrombocytopenia (low platelets), increasing their susceptibility to frequent infections and uncontrolled bleeding. Some cases are further complicated by hepatosplenomegaly—enlargement of the liver and spleen—indicating systemic involvement.

Diagnostic blood tests typically reveal cytopenias across one, two, or all three major blood cell lines. Because of these abnormalities, pediatric MDS is often considered a pre-leukemic condition, carrying a significant risk of progression to acute myeloid leukemia (AML) if not properly managed.

Potential Causes and Contributing Factors

While the exact cause of pediatric myelodysplastic syndrome remains unclear, researchers have identified several environmental and biological factors that may contribute to its development. Exposure to certain toxic chemicals—particularly benzene and its derivatives—has been linked to bone marrow damage. Benzene, commonly found in industrial solvents, fuels, and some household products, is known to interfere with normal hematopoiesis.

Environmental and Infectious Triggers

In addition to chemical exposure, prolonged contact with pesticides and other agricultural chemicals may elevate the risk. Viral infections, especially hepatitis viruses, have also been associated with bone marrow dysfunction in genetically predisposed individuals. These infections may trigger inflammatory responses that disrupt stem cell regulation.

Genetic and Familial Influences

There is growing evidence that genetics play a critical role in pediatric MDS. Children with a family history of hematologic malignancies—including leukemia, lymphoma, or other bone marrow disorders—are at higher risk. Inherited genetic syndromes such as Fanconi anemia, Shwachman-Diamond syndrome, and Diamond-Blackfan anemia are strongly correlated with the development of MDS.

The underlying pathology involves chromosomal abnormalities, including deletions or mutations that lead to dysregulation of oncogenes and tumor suppressor genes. These genetic alterations impair normal cell differentiation and promote the survival of defective blood cells. Furthermore, immune system dysregulation may contribute to the destruction of healthy hematopoietic cells, exacerbating the cytopenias seen in affected children.

Conclusion and Clinical Implications

Although pediatric myelodysplastic syndrome is rare, early recognition and comprehensive evaluation are essential for improving long-term outcomes. Understanding the interplay between environmental exposures, viral triggers, and genetic predisposition helps clinicians identify at-risk children and implement timely interventions. Ongoing research into molecular mechanisms continues to shed light on potential targeted therapies, offering hope for more effective treatments in the future.