ABSTRACT

Background: Stickler syndrome is a hereditary disorder of collagen tissues causing ocular, auditory, orofacial, and joint manifestations. Ocular findings typically include vitreous degeneration, high myopia, retinal detachment, and cataract. Many subjects demonstrate sensorineural or conductive hearing loss. The inheritance is autosomal dominant with mutations in COL2A1, COL11A1, or COL11A2 or autosomal recessive due to mutations in COL9A1, COL9A2, or COL9A3. We describe a family with Stickler syndrome caused by homozygous loss-of-function mutations in COL9A2.

Methods: Two brothers from a consanguineous family were examined with genetic testing, visual acuity, Goldmann perimetry, full-field and multifocal electroretinography (ffERG, mERG), optical coherence tomography (OCT), fundus autofluorescence (FAF), fundus photography, and pure-tone audiograms.

Results: Both subjects were homozygous for the mutation c.1332del in COL9A2. Their parents were heterozygous for the same mutation. The boys demonstrated reduced visual acuity, vitreous changes and myopia. The proband was operated for retinal detachment and cataract in one eye. FfERG revealed reduced function of both rods and cones and mERG showed reduced macular function. No morphological macular changes were found by OCT or FAF. Both brothers have severe sensorineural hearing loss with down-sloping audiograms but only subtle midface hypoplasia and no, or mild joint problems.

Conclusion: Only a few families with Stickler syndrome caused by COL9A2 mutations have been reported. We confirm previous descriptions with a severe ocular and auditory phenotype but mild orofacial and joint manifestations. Moreover, we demonstrate reduced macular and overall retinal function explaining the reduced visual acuity in patients with Stickler syndrome also without retinal complications.

摘要

背景：Stickler 综合征是一种胶原组织的遗传性疾病，可导致眼、耳、口面部和关节表现。眼部表现通常包括玻璃体变性、高度近视、视网膜脱离和白内障。许多受试者表现出感音神经性或传导性听力损失。该遗传是常染色体显性遗传，COL2A1、COL11A1或COL11A2突变，或由于COL9A1、COL9A2或COL9A3突变导致的常染色体隐性遗传。我们描述了一个由COL9A2 中纯合子功能丧失突变引起的Stickler综合征家族。

方法：对近亲家庭的两兄弟进行基因检测、视力、戈德曼视野检查、全视野和多焦视网膜电图（ffERG、mERG）、光学相干断层扫描（OCT）、眼底自发荧光（FAF）、眼底照相和纯-音听力图。

结果：这两个问题为纯合子的突变c.1332del COL9A2。他们的父母是相同突变的杂合子。这些男孩表现出视力下降、玻璃体变化和近视。先证者因一只眼睛的视网膜脱离和白内障接受了手术。FfERG 显示视杆和视锥细胞功能降低，mERG 显示黄斑功能降低。OCT 或 FAF 未发现黄斑部形态学改变。两兄弟都有严重的感音神经性听力损失，听力图呈向下倾斜，但只有轻微的面部中部发育不全，没有或轻微的关节问题。

结论：只有少数COL9A2突变引起的Stickler综合征家族被报道。我们确认先前的描述具有严重的眼部和听觉表型，但有轻微的口面部和关节表现。此外，我们证明了黄斑部和整体视网膜功能降低，这解释了 Stickler 综合征患者视力下降，也没有视网膜并发症。