Department of Otolaryngology-Head & Neck Surgery, University of California, San Francisco.
JAMA Netw Open. 2022 Sep 1;5(9):e2233441. doi: 10.1001/jamanetworkopen.2022.33441.
A genetic diagnosis can help elucidate the prognosis of hearing loss, thus significantly affecting management. Previous studies on diagnostic yield of hearing loss genetic tests have been based on largely homogenous study populations.
To examine the diagnostic yield of genetic testing in a diverse population of children, accounting for sociodemographic and patient characteristics, and assess whether these diagnoses are associated with subsequent changes in clinical management.
DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included 2075 patients seen at the Children's Communications Clinic, of whom 517 completed hearing loss gene panel testing between January 1, 2015, and November 1, 2021, at the University of California, San Francisco Benioff Children's Hospital system. From those 517 patients, 426 children with at least 2 audiograms were identified and analyzed. Data were gathered from November 2021 to January 2022 and analyzed from January to February 2022.
The measures of interest were sociodemographic characteristics (age at testing, gender, race and ethnicity, primary language, and insurance type), hearing loss characteristics, and medical variables. The outcome was genetic testing results. Variables were compared with univariate and multivariable logistic regression.
Of the 2075 patients seen at the Children's Communications Clinic, 517 (median [range] age, 8 [0-31] years; 264 [51.1%] male; 351 [67.9%] from an underrepresented minority [URM] group) underwent a hearing loss panel genetic test between January 1, 2015, and November 1, 2021. Among those 517 patients, 426 children (median [range] age, 8 [0-18] years; 221 [51.9%] male; 304 [71.4%] from an URM group) with 2 or more audiograms were included in a subsequent analysis. On multivariable logistic regression, age at testing (odds ratio [OR], 0.87; 95% CI, 0.78-0.97), URM group status (OR, 0.29; 95% CI, 0.13-0.66), comorbidities (OR, 0.27; 95% CI, 0.14-0.53), late-identified hearing loss (passed newborn hearing screen; OR, 0.27; 95% CI, 0.08-0.86), and unilateral hearing loss (OR, 0.04; 95% CI, 0.005-0.33) were the only factors associated with genetic diagnosis. No association was found between genetic diagnosis yield and other sociodemographic variables or hearing loss characteristics. Patients in URM and non-URM groups had statistically similar clinical features. A total of 32 of 109 children (29.4%) who received a genetic diagnosis received diagnoses that significantly affected prognosis because of identification of syndromic or progressive sensorineural hearing loss or auditory neuropathy spectrum disorder relating to otoferlin.
This cohort study's findings suggest that genetic testing may be broadly useful in improving clinical management of children with hearing loss. More research is warranted to discover and characterize diagnostic genes for those who have been historically underrepresented in research and medicine.
基因诊断有助于阐明听力损失的预后，从而显著影响管理。先前关于听力损失基因检测诊断率的研究主要基于高度同质的研究人群。
在一个多样化的儿童人群中检查基因检测的诊断率，考虑社会人口统计学和患者特征，并评估这些诊断是否与后续临床管理的变化相关。
设计、设置和参与者：这是一项回顾性队列研究，纳入了在加利福尼亚大学旧金山分校 Benioff 儿童医院系统的儿童沟通诊所就诊的 2075 名患者，其中 517 名患者在 2015 年 1 月 1 日至 2021 年 11 月 1 日期间完成了听力损失基因面板检测。在这 517 名患者中，确定了 426 名至少有 2 次听力图的儿童进行了分析。数据于 2021 年 11 月收集，并于 2022 年 1 月至 2 月进行分析。
感兴趣的测量指标包括社会人口统计学特征（检测时的年龄、性别、种族和民族、主要语言和保险类型）、听力损失特征和医疗变量。结果是基因检测结果。将变量与单变量和多变量逻辑回归进行比较。
在儿童沟通诊所就诊的 2075 名患者中，517 名（中位数[范围]年龄 8[0-31]岁；264[51.1%]男性；351[67.9%]来自代表性不足的少数族裔[URM]群体）在 2015 年 1 月 1 日至 2021 年 11 月 1 日期间接受了听力损失面板基因检测。在这 517 名患者中，426 名（中位数[范围]年龄 8[0-18]岁；221[51.9%]男性；304[71.4%]来自 URM 群体）有 2 次或更多次听力图，随后进行了分析。在多变量逻辑回归中，检测时的年龄（比值比[OR]，0.87；95%CI，0.78-0.97）、URM 群体状态（OR，0.29；95%CI，0.13-0.66）、合并症（OR，0.27；95%CI，0.14-0.53）、后期发现的听力损失（通过新生儿听力筛查；OR，0.27；95%CI，0.08-0.86）和单侧听力损失（OR，0.04；95%CI，0.005-0.33）是唯一与基因诊断相关的因素。基因诊断率与其他社会人口统计学变量或听力损失特征之间没有关联。URM 和非 URM 组的患者在临床特征方面具有统计学上的相似性。在接受基因诊断的 109 名儿童中，有 32 名（29.4%）被诊断出患有综合征或进行性感音神经性听力损失或与 otoferlin 相关的听觉神经病谱系障碍，这显著影响了预后。
这项队列研究的结果表明，基因检测可能在改善听力损失儿童的临床管理方面具有广泛的应用价值。需要进一步研究以发现和描述那些在研究和医学中历史上代表性不足的人的诊断基因。
