Genomic insights into inherited bone marrow failure syndromes: a single-center clinical study

Abstract

Aim: Inherited Bone Marrow Failure Syndromes (IBMFS) are increasingly diagnosed in both pediatrics and adults presenting with cytopenias, myelodysplastic syndrome, and acute leukemia due to increased awareness among providers. Given the multi-organ involvement in IBMFS, the referrals for genetic testing have extended to individuals with pulmonary fibrosis, liver cirrhosis, and concerns for cancer predisposition in other solid tumors. The purpose of this study is to highlight the real-world data of genetic testing in an Inherited Bone Marrow Failure clinic and the challenges faced.

Method: Patients who were referred to the Medical Genetics and Genomics Outpatient Clinic for evaluation of a suspected underlying IBMFS at the University of Iowa from January 2023 to September 2024 were enrolled in this study. Clinical phenotypes, reasons for referrals, and genetic testing results were recorded and analyzed.

Result: A total of 16 individuals from 15 families were enrolled in this study during this period. Clinical-grade genetic testing yielded a diagnosis in 50% of the patients, with a predominance of patients diagnosed with a telomere biology disorder.

Conclusion: Early diagnosis of an underlying IBMFS is important to reduce mortality and morbidity. Genomic testing is crucial to provide an accurate diagnosis and appropriate management, including donor selection when hematopoietic stem cell transplant is a treatment option.

Keywords

Inherited bone marrow failure syndromes / myelodysplastic syndrome / acute leukemia / pulmonary fibrosis / liver cirrhosis / cancer predisposition to solid tumors

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