Abstract
Alport syndrome is a genetically heterogeneous disorder with X-linked, autosomal dominant, autosomal recessive, and digenic inheritance patterns. The X-linked form, most commonly due to COL4A5 mutations, is the most prevalent and typically results in more severe disease in males, while heterozygous females are usually less severely affected. Autosomal recessive Alport syndrome arises from biallelic mutations in COL4A3 or COL4A4 and often mirrors the severity seen in X-linked males. Autosomal dominant Alport syndrome, involving a single pathogenic allele in COL4A3 or COL4A4, generally leads to later-onset and milder renal involvement. Digenic inheritance—pathogenic variants in two of COL4A3, COL4A4, or COL4A5—produces variable clinical phenotypes. Accurate delineation of these inheritance patterns is crucial for predicting disease severity and informing prognosis and genetic counseling. Advances in next-generation sequencing have improved diagnostic precision, enabling detection of mosaicism, complex rearrangements, and variants with atypical or milder presentations. Research into modifier genes and epigenetic influences may further refine individualized management strategies.
Keywords
Alport syndrome, COL4A3, COL4A4, COL4A5, X-linked inheritance, Autosomal dominant, Autosomal recessive, Digenic inheritance, Hematuria, Proteinuria, End-stage renal disease, Sensorineural hearing loss, Anterior lenticonus, Ocular abnormalities, Genotype-phenotype correlation, Next-generation sequencing, Genetic counseling, Renal pathology, Family history, Mutation analysis, Molecular diagnosis, Collagen IV, Basement membrane, Kidney biopsy, Clinical diagnosis, Genetic testing, Inheritance patterns