Abstract：
OBJECTIVE: Gene therapy for monogenic hearing loss is on the horizon. The first trials in patients with Auditory Neuropathy Spectrum Disorder (ANSD) due to pathogenic variants in the Otoferlin (OTOF) gene will open this year. In the UK, the new NHS Genomic Medicine Service (GMS) offers genetic testing in each child diagnosed with congenital or early onset sensorineural hearing loss. This survey study aims to map preexisting clinical pathways for the diagnosis and management of children with ANSD and identify opportunities for improvement in early identification of OTOF- related ANSD.
METHODS: A Google form with 24 questions in English covering the ANSD clinical pathway was developed with clinicians involved in the diagnosis and management ANSD. The survey was disseminated via email to all Lead clinicians of NHS Tertiary Paediatric Audiology and Cochlear Implant Services within the UK.
RESULTS: Data was received from 27 (34 %) NHS Tertiary Paediatric Audiology Services and 8 (n = 57 %) Paediatric Cochlear Implant Services. Services follow existing national guidance and provide multidisciplinary care with structured patient pathways for referral, diagnosis, and management of children with ANSD and multidisciplinary input throughout. Clinicians are aware of the genetic causes of ANSD and new processes for genetic testing, but do not uniformly refer children with ANSD for testing for OTOF pathogenic variants. As such, they had difficulty estimating numbers of children with OTOF pathogenic variants under their care.
CONCLUSIONS: Those results highlight the urgency of implementing hearing gene panel sequencing for all children with ANSD to provide opportunities for early diagnosis and candidacy for OTOF gene therapy trials.
METHODS: A Google form with 24 questions in English covering the ANSD clinical pathway was developed with clinicians involved in the diagnosis and management ANSD. The survey was disseminated via email to all Lead clinicians of NHS Tertiary Paediatric Audiology and Cochlear Implant Services within the UK.
RESULTS: Data was received from 27 (34 %) NHS Tertiary Paediatric Audiology Services and 8 (n = 57 %) Paediatric Cochlear Implant Services. Services follow existing national guidance and provide multidisciplinary care with structured patient pathways for referral, diagnosis, and management of children with ANSD and multidisciplinary input throughout. Clinicians are aware of the genetic causes of ANSD and new processes for genetic testing, but do not uniformly refer children with ANSD for testing for OTOF pathogenic variants. As such, they had difficulty estimating numbers of children with OTOF pathogenic variants under their care.
CONCLUSIONS: Those results highlight the urgency of implementing hearing gene panel sequencing for all children with ANSD to provide opportunities for early diagnosis and candidacy for OTOF gene therapy trials.
摘要：
目的：单基因听力损失的基因治疗即将到来。由于Otoferlin（OTOF）基因的致病变异而导致的听觉神经病谱系障碍（ANSD）患者的第一项试验将于今年开始。在英国,新的NHS基因组医学服务(GMS)为每个被诊断患有先天性或早发性感音神经性听力损失的儿童提供基因检测.这项调查研究旨在绘制先前存在的临床路径，以诊断和管理ANSD儿童，并确定改善OTOF相关ANSD早期识别的机会。
方法：由参与ANSD诊断和管理的临床医生开发了包含24个英文问题的Google表格。该调查通过电子邮件分发给英国NHS三级儿科听力学和耳蜗植入服务的所有首席临床医生。
结果：数据来自27（34％）NHS三级儿科听力学服务和8（n=57％）儿科耳蜗植入服务。服务遵循现有的国家指南，并通过结构化的患者转诊路径提供多学科护理，诊断,以及对患有ANSD和多学科投入的儿童的管理。临床医生意识到ANSD的遗传原因和基因检测的新过程，但不要统一推荐患有ANSD的儿童进行OTOF致病变异的检测.因此，他们很难估计在他们护理下患有OTOF致病变异的儿童的数量.
结论：这些结果强调了对所有ANSD儿童实施听力基因小组测序的紧迫性，为OTOF基因治疗试验的早期诊断和候选提供机会。
方法：由参与ANSD诊断和管理的临床医生开发了包含24个英文问题的Google表格。该调查通过电子邮件分发给英国NHS三级儿科听力学和耳蜗植入服务的所有首席临床医生。
结果：数据来自27（34％）NHS三级儿科听力学服务和8（n=57％）儿科耳蜗植入服务。服务遵循现有的国家指南，并通过结构化的患者转诊路径提供多学科护理，诊断,以及对患有ANSD和多学科投入的儿童的管理。临床医生意识到ANSD的遗传原因和基因检测的新过程，但不要统一推荐患有ANSD的儿童进行OTOF致病变异的检测.因此，他们很难估计在他们护理下患有OTOF致病变异的儿童的数量.
结论：这些结果强调了对所有ANSD儿童实施听力基因小组测序的紧迫性，为OTOF基因治疗试验的早期诊断和候选提供机会。
