Usher syndrome(USH)should no longer be considered a fixed diagnosis limited to syndromic early-onset sensorineural hearing loss and progressive vision decline due to rod-cone retinal dystrophy.Patients increasingly pr...Usher syndrome(USH)should no longer be considered a fixed diagnosis limited to syndromic early-onset sensorineural hearing loss and progressive vision decline due to rod-cone retinal dystrophy.Patients increasingly present with partial or delayed retinal manifestations,often lacking a clinically relevant audiological history.Concurrently,genomic testing uncovers variants that challenge the practical relevance of the traditional definition of type I,II,and III subclassifications.This review argues for a paradigm shift toward genotype-first diagnosis led by ophthalmologists,integrating retinal findings and audiological evaluations with comprehensive genetic information.The rise of gene-specific molecular therapies,including antisense oligonucleotides and CRISPR-mediated gene editing for USH2A and MYO7A,demands timely and accurate molecular categorization for each patient.Delays in precise molecular diagnosis may risk excluding patients from potentially vision-saving trials.Diagnostic gaps persist,including limited variant interpretation tools,underrepresentation of non-Caucasian populations in reference databases,and a lack of standardized retinal imaging protocols.The establishment of centralized,real-time Usher registries and interdisciplinary diagnostic models is essential.The future of USH management lies in anticipatory,individualized care that begins in the retina clinic.展开更多
文摘Usher syndrome(USH)should no longer be considered a fixed diagnosis limited to syndromic early-onset sensorineural hearing loss and progressive vision decline due to rod-cone retinal dystrophy.Patients increasingly present with partial or delayed retinal manifestations,often lacking a clinically relevant audiological history.Concurrently,genomic testing uncovers variants that challenge the practical relevance of the traditional definition of type I,II,and III subclassifications.This review argues for a paradigm shift toward genotype-first diagnosis led by ophthalmologists,integrating retinal findings and audiological evaluations with comprehensive genetic information.The rise of gene-specific molecular therapies,including antisense oligonucleotides and CRISPR-mediated gene editing for USH2A and MYO7A,demands timely and accurate molecular categorization for each patient.Delays in precise molecular diagnosis may risk excluding patients from potentially vision-saving trials.Diagnostic gaps persist,including limited variant interpretation tools,underrepresentation of non-Caucasian populations in reference databases,and a lack of standardized retinal imaging protocols.The establishment of centralized,real-time Usher registries and interdisciplinary diagnostic models is essential.The future of USH management lies in anticipatory,individualized care that begins in the retina clinic.
