关键词: Waardenburg综合征, 虹膜异色, 内眦外移, 遗传病

Abstract: Waardenburg syndrome (WS) is a group of rare congenital hereditary disorders characterized by high clinical and genetic heterogeneity, with sensorineural hearing loss and pigment distribution abnormalities in hair, skin, and irises as the primary features. In recent years, the widespread application of high-throughput sequencing technologies has significantly expanded its molecular genetic landscape. Currently, pathogenic variants in at least six genes (e.g., PAX3, MITF, SOX10, SNAI2, EDNRB, EDN3) have been identified as associated with the four major clinical subtypes of WS. Extensive studies on de novo mutations and genotype-phenotype correlations have continually deepened our understanding of the disease spectrum. At the pathological mechanism level, research has focused on the central regulatory roles of these genes in neural crest cell development, melanocyte migration and differentiation, and stria vascularis function in the inner ear, revealing a complex network involving transcriptional regulation, signaling pathways (e.g., the endothelin pathway), and cell-cell interactions. Current research frontiers have shifted from genetic diagnosis to in-depth exploration of disease mechanisms and potential therapeutic strategies, including CRISPR/Cas9-based gene editing, antisense oligonucleotide mediated correction of aberrant splicing, small-molecule drug interventions, and stem cell therapies. With the continuous advancement of gene sequencing technologies, an increasing number of pathogenic mutations are being discovered, offering possibilities for unraveling disease mechanisms and developing treatments. 

Key words: Waardenburg syndrome, Iris heterochromia, Dystopia canthorum, Hereditary disorders