Alport Syndrome: Molecular Pathogenesis, Diagnostic Frontier and Clinical Management- Singaporean Experience

Although genetic testing achieves diagnostic yields of 20–35%, limitations remain, particularly variants of uncertain significance and false negatives. Syndromic features and family history continue to provide critical diagnostic clues, while kidney biopsy and electron microscopy retain value where genomics is unavailable. Case vignettes from Singapore illustrate how reverse phenotyping after genetic diagnosis can uncover extra‑renal manifestations and guide holistic care. Clinical management emphasizes early initiation of ACE inhibitor or ARB therapy, systematic monitoring for hearing and ocular involvement, and family cascade testing for early detection and safe donor selection. Singapore’s integration of genomic testing into clinical pathways, collaboration with the National Precision Medicine Programme (PRECISE), and recognition of barriers such as cost, access, and underrepresentation of Asian populations highlight both innovation and ongoing challenges.