Conventional Karyotyping in Down Syndrome: Diagnostic Relevance in the Molecular Era

Down syndrome (DS), also known as trisomy 21, is the most common chromosomal aberration, characterized by global intellectual disability and developmental defects. The syndrome results from an extra copy of chromosome 21, leading to gene dosage changes and normal development. Cytogenetically, DS has been classified into complete trisomy 21, Robertsonian translocation trisomy 21 and mosaic trisomy 21, with different mechanisms of occurrence and recurrence risks. Diagnosis is important for confirming disease, prognosis, prenatal diagnosis, recurrence risk and genetic counselling. Traditional karyotyping has been the gold standard of cytogenetic diagnosis for a long time, as it allows observation of the chromosomes and detection of both numeric and structural abnormalities. Traditional cytogenetics still has clinical value, despite modern diagnostic methods (FISH, chromosomal microarray analysis, quantitative fluorescent PCR, next-generation sequencing, and non-invasive prenatal testing) providing better efficiency, speed and genomic data. It is particularly required for the diagnosis of balanced translocations, chromosomal rearrangements and low-level mosaicism that may escape detection by molecular methods. Moreover, recent advances in artificial intelligence, digital karyotyping and cytogenomic platforms have significantly improved the efficiency of cytogenetic analysis. This review attempts to impart the cytogenetics of DS, the role of conventional karyotyping, the new molecular diagnostic methods, a comparison between the conventional and molecular approaches, technological advances and future perspectives on the integration of genomics in diagnostics while emphasizing the continued importance of classical karyotyping despite ongoing advances in molecular technology.

Down syndrome, trisomy 21, conventional karyotyping, cytogenetics.

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