Cochlear Implant Center, Department of Otolaryngology/Head, Neck & Maxillofacial Surgery, Tel-Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel-Aviv, Israel.
Otopathology Laboratory, Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts.
Otol Neurotol. 2018 Jun;39(5):e387-e391. doi: 10.1097/MAO.0000000000001801.
: Cockayne syndrome (CS) is a rare autosomal recessive syndrome resulting in defective DNA repair. Its features include cachectic dwarfism, hearing loss, skin hypersensitivity to sunlight, premature aging, and dementia. Presented is a right temporal bone of a patient who died at the age of 29 years. The clinical course was compatible with type 1 CS, the classical form. Homozygous missense variant in the ERCC6 gene (Excision Repair Cross-Complementation group 6) was found, compatible with CS complementation group B. Five years before his death he complained of tinnitus. An audiogram 3 and a 1/2 years before his death demonstrated a moderate symmetrical sensorineural hearing loss at 2 to 8 kHz. The speech reception threshold was 20 dB, and the word recognition score was 100% on the right.Histopathology revealed a near normal population of inner hair cells except in the basal 5 mm of the cochlea, and mild loss of outer hair cells particularly at the base of the cochlea. Severe atrophy of the spiral ligament and atrophy of stria vascularis and spiral prominence was present. There was loss of Claudius cells, outer sulcus cells, and mesenchymal cells on the scala tympani side of the basilar membrane and loss of cellularity of the limbus. There was a moderate loss of Scarpa's and spiral ganglion neurons, with the most severe loss in the basal segment. The vestibular neuro-epithelium was nearly intact, with the exception of mild loss in the saccule. The vestibular perilymphatic, and to a lesser extent endolymphatic spaces, were filled with filamentous material and osteoid. The patient had better hearing and a larger complement of neurons compared with the few published case reports.Neurodegenerative symptoms are likely attributed to the effect of intramitochondrial reactive oxygen species. The pathogenesis of hearing loss in CS may shed light on other causes of hearing loss, such as that induced by noise.
科凯恩综合征(CS)是一种罕见的常染色体隐性遗传综合征,导致 DNA 修复缺陷。其特征包括消瘦型侏儒、听力损失、皮肤对阳光过敏、早衰和痴呆。本文介绍了一位 29 岁死亡患者的右颞骨。临床表现符合 1 型 CS(经典型)。发现 ERCC6 基因(切除修复交叉互补组 6)纯合错义变异,与 CS 补体组 B 相符。他在去世前 5 年抱怨耳鸣。去世前 3 年和 1/2 年前的听力图显示 2 至 8kHz 处中度对称感音神经性听力损失。言语接受阈为 20dB,右侧单词识别得分为 100%。组织病理学显示内毛细胞的正常群体,除了耳蜗底部的近 5mm 外,外毛细胞轻度丢失,尤其是耳蜗基底。螺旋韧带严重萎缩,血管纹和螺旋嵴萎缩。Basilar 膜的鼓阶 Claudius 细胞、外沟细胞和间质细胞丢失,嵴细胞的细胞结构丢失。螺旋神经节神经元有中度丢失,基底段丢失最严重。前庭神经上皮几乎完整,除了椭圆囊有轻微丢失。前庭外淋巴液和内淋巴液,程度较轻,充满丝状物质和类骨质。与少数已发表的病例报告相比,该患者的听力更好,神经元数量更多。神经退行性症状可能归因于线粒体活性氧的影响。CS 听力损失的发病机制可能为其他原因引起的听力损失(如噪声诱导的听力损失)提供线索。