Down Syndrome due to de Novo Robertsonian Translocation Rob(21;21) in Mali

ABSTRACT Down syndrome (DS) is the most common chromosomal disorder among live births, most frequently resulting from free trisomy 21. Robertsonian translocations, which arise from the fusion of acrocentric chromosomes, represent a rare but clinically significant mechanism underlying DS. Among these rearrangements, the Robertsonian translocation rob (21;21) is rare, with only a limited number of cases reported worldwide. We report two unrelated Malian patients presenting phenotype consisting with DS. Comprehensive cytogenetic analysis, combining conventional karyotyping and fluorescence in situ hybridization (FISH), enabled accurate detection and detailed characterization of both trisomy 21 and the associated rob (21;21)(q10;10) translocations, representing the first such cases identified in Mali. Parental karyotyping and FISH analyses revealed normal chromosome complements, supporting a de novo origin in both cases. These cases underscore the critical role of cytogenetic investigations in accurately diagnosing DS and in identifying the de novo occurrence of rob (21;21). They further highlight the importance of strengthening cytogenetic capacity in resource‐limited settings such as Mali, where genomic medicine is still emerging, and have important implications for genetic counseling and recurrence risk assessment.