遺伝性骨髄不全症候群の遺伝的洞察と診断上の課題：低中所得国からの包括的研究
Syed Ibrahim Bukhari1, Fizza Akbar2, Salman Kirmani2
1Department of Oncology, Aga Khan University, Karachi, Pakistan.
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.
