一例耳蜗形态正常的Warsaw断裂综合征患儿同期双侧人工耳蜗植入：病例报告及聚焦文献复习

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中文摘要

背景与临床意义： Warsaw断裂综合征（WABS），又称DDX11相关黏连蛋白病，是一种由DDX11双等位基因致病变异引起的极为罕见的常染色体隐性遗传病。感音神经性听力损失是其反复出现的表现，并常与耳蜗或耳蜗神经的结构异常同时被报道。关于WABS患者人工耳蜗植入的已发表经验仍极为有限。病例介绍：一名2.5岁男孩因缺乏口语发育以及对环境声和言语声反应有限而被转诊。未进行新生儿听力筛查。在治疗双侧中耳积液后，全面听力学评估显示瞬态诱发耳声发射和耳蜗微音电位缺失，在最大测试水平90 dB nHL下无可重复的听性脑干反应波形，听性稳态反应估计为双侧重度至极重度范围。临床检查发现小头畸形、身材矮小和全面发育迟缓，提示可能存在潜在综合征性疾病。高分辨率计算机断层扫描显示耳蜗形态正常，而磁共振成像显示双侧耳蜗神经可见，无发育不全或明显发育不良。全外显子组测序发现DDX11存在一个致病性移码变异，呈 apparent 纯合状态，支持WABS的分子诊断。患儿3岁时接受同期双侧人工耳蜗植入，无并发症。采用LittlEARS听觉问卷评估的纵向听觉发育从开机时的0/35改善至听觉年龄8个月时的10/35、20个月时的21/35和24个月时的33/35。在听觉年龄约30个月时，结构化语言评估显示接受性和表达性交流进一步改善，尽管语言发育仍受潜在神经发育障碍的影响。在听觉年龄33个月时，采用PEACH-GR评估的功能性听觉表现为安静环境下90%、噪声环境下80%、总体85%，而希腊语标准化语言测试显示相对于实足年龄预期仍存在持续性语言困难。结论：WABS中的重度至极重度语前感音神经性听力损失可在耳蜗形态正常且双侧耳蜗神经可见的情况下发生。在该患者中，同期双侧人工耳蜗植入在技术上无并发症。在随后的双侧设备使用、调机、康复和成熟过程中，观察到有定量记录的进行性听觉发育和功能性交流改善。全面的听力学、影像学、遗传学和发育评估对于个体化植入候选资格评估和现实的家属咨询至关重要。

英文摘要

Background and Clinical Significance: Warsaw Breakage Syndrome (WABS), also termed DDX11-related cohesinopathy, is an exceptionally rare autosomal recessive disorder caused by biallelic pathogenic variants in DDX11. Sensorineural hearing loss is a recurrent manifestation and has frequently been reported together with structural abnormalities of the cochlea or cochlear nerve. Published experience with cochlear implantation in WABS remains extremely limited. Case Presentation: A 2.5-year-old boy was referred because of absent spoken-language development and limited responses to environmental and speech sounds. Newborn hearing screening had not been performed. After treatment of bilateral middle-ear effusions, comprehensive audiological assessment showed absent transient-evoked otoacoustic emissions and cochlear microphonics, no reproducible auditory brainstem response waveforms at the maximum tested level of 90 dB nHL, and auditory steady-state response estimates in the severe-to-profound range bilaterally. Clinical examination revealed microcephaly, short stature, and global developmental delay, raising suspicion of an underlying syndromic disorder. High-resolution computed tomography demonstrated normal cochlear morphology, while magnetic resonance imaging showed bilaterally visualized cochlear nerves without aplasia or marked hypoplasia. Whole-exome sequencing identified a pathogenic frameshift variant in DDX11 in apparent homozygosity, supporting the molecular diagnosis of WABS. Simultaneous bilateral cochlear implantation was performed at 3 years of age without complications. Longitudinal auditory development, assessed with the LittlEARS Auditory Questionnaire, improved from 0/35 at activation to 10/35 at 8 months, 21/35 at 20 months, and 33/35 at 24 months of auditory age. At approximately 30 months of auditory age, structured language assessments demonstrated further receptive and expressive communication gains, although language development remained influenced by the underlying neurodevelopmental disorder. At 33 months of auditory age, functional auditory performance assessed with PEACH-GR was 90% in quiet, 80% in noise, and 85% overall, while Greek-standardized language testing demonstrated persistent language difficulties relative to chronological-age expectations. Conclusions: Severe-to-profound prelingual sensorineural hearing loss in WABS may occur despite normal cochlear morphology and bilaterally visualized cochlear nerves. In this patient, simultaneous bilateral cochlear implantation was technically uncomplicated. During subsequent bilateral device use, programming, rehabilitation, and maturation, quantitatively documented progressive auditory development and functional communication gains were observed. Comprehensive audiological, radiological, genetic and developmental assessment is essential for individualized implant candidacy and realistic family counseling.