Genetic insights and diagnostic challenges in inherited bone marrow failure syndromes: A comprehensive study from a low middle-income country

Authors

Syed Ibrahim Bukhari, Aga Khan UniversityFollow
Fizza Akbar, Aga Khan UniversityFollow
Salman Kirmani, Aga Khan UniversityFollow
Zehra Fadoo, Aga Khan UniversityFollow
Asim Belgaumi, Aga Khan UniversityFollow
Sadaf Altaf, Aga Khan UniversityFollow

Document Type

Article

Department

Haematology/Oncology; Women and Child Health; Paediatrics and Child Health

Abstract

Background: Inherited bone marrow failure syndromes (IBMFS) often present with overlapping features and may be misdiagnosed as idiopathic aplastic anemia (iAA). Genetic testing is critical for accurate diagnosis, especially in consanguineous populations.
Research design and methods: We retrospectively analyzed 41 pediatric patients who underwent genetic evaluation for suspected bone marrow failure. Clinical features, diagnostic classifications, and genetic findings were reviewed to assess diagnostic yield and impact.
Results: The cohort included 21 males and 20 females (median age: 8 years). Pancytopenia was the most common presentation (27/41; 65%), half (20/41; 49%) were products of consanguineous marriage. iAA was the initial diagnosis in 56% (23/41). Genetic testing identified pathogenic/likely pathogenic (P/LP) variants in 14 patients (34%), enabling a molecular diagnosis. An additional 13 patients (32%) had variants of uncertain significance, one of which was later reclassified as LP, confirming Noonan syndrome. Genetic findings prompted diagnostic revisions, including Fanconi anemia, Congenital Amegakaryocytic Thrombocytopenia, Shwachman-Diamond syndrome, and Diamond-Blackfan anemia. Commonly affected genes included MPL, FANCA, followed by DANJC21.
Conclusions: In this Pakistani cohort, genetic testing clarified IBMFS diagnoses in 34% of cases, matching global yields. It enhanced diagnostic precision, informed management, and supported family counseling, though high VUS rates underscore the need for ongoing reclassification and multidisciplinary care.

Comments

Volume and issue number is not provided by the author/publisher.

AKU Student

no

Publication (Name of Journal)

Expert Review of Hematology

DOI

10.1080/17474086.2025.2610748

Recommended Citation

Bukhari, S. I., Akbar, F., Kirmani, S., Fadoo, Z., Belgaumi, A., Altaf, S. (2025). Genetic insights and diagnostic challenges in inherited bone marrow failure syndromes: A comprehensive study from a low middle-income country. Expert Review of Hematology, 1-11.
Available at: https://ecommons.aku.edu/pakistan_fhs_mc_radiat_oncol/146