Ocular phenotype and therapeutic interventions in keratitis-ichthyosis-deafness (KID) syndrome.

IF 1.2 4区 医学 Q4 GENETICS & HEREDITY
Ophthalmic Genetics Pub Date : 2024-02-01 Epub Date: 2024-01-26 DOI:10.1080/13816810.2023.2258218
Keri Mc Lean, Stefano Bignotti, Michele Callea, Francisco Cammarata-Scalisi, Bernhard Steger, David Armstrong, Maeve Lagan, Janet Sinton, Francesco Semeraro, Stephen B Kaye, Vito Romano, Colin E Willoughby
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引用次数: 0

Abstract

Background: To report ocular manifestations, clinical course, and therapeutic management of patients with molecular genetically confirmed keratitis-ichthyosis-deafness syndrome.

Methods: Four patients, aged 19 to 46, with keratitis-ichthyosis-deafness syndrome from across the UK were recruited for a general and ocular examination and GJB2 (Cx26) mutational analysis. The ocular examination included best-corrected visual acuity, slit-lamp bio-microscopy, and ocular surface assessment. Mutational analysis of the coding region of GJB2 (Cx26) was performed by bidirectional Sanger sequencing.

Results: All four individuals had the characteristic systemic features of keratitis-ichthyosis-deafness syndrome. Each patient was found to have a missense mutation, resulting in the substitution of aspartic acid with asparagine at codon 50 (p.D50N). Main ophthalmic features were vascularizing keratopathy, ocular surface disease, hyperkeratotic lid lesions, recurrent epithelial defects, and corneal stromal scarring. One patient had multiple surgical procedures, including superficial keratectomies and lamellar keratoplasty, which failed to prevent severe visual loss. In contrast, oral therapy with ketoconazole stabilized the corneal and skin disease in two other patients with keratitis-ichthyosis-deafness syndrome. The patient who underwent intracorneal bevacizumab injection showed a marked reduction in corneal vascularization following a single application.

Conclusions: Keratitis-ichthyosis-deafness syndrome is a rare ectodermal dysplasia caused by heterozygous mutations in GJB2 (Cx26) with a severe, progressive vascularizing keratopathy. Oral ketoconazole therapy may offer benefit in stabilizing the corneal and skin disease.

角膜炎-鱼鳞病-耳聋(KID)综合征的眼部表型和治疗干预。
背景:报道分子遗传学证实的角膜炎-鱼鳞病-耳聋综合征患者的眼部表现、临床病程和治疗方法。方法:从英国各地招募4名年龄在19至46岁的角膜炎-鱼鳞病-耳聋综合征患者进行全身和眼部检查,并进行GJB2(Cx26)突变分析。眼部检查包括最佳矫正视力、裂隙灯生物显微镜和眼表评估。通过双向Sanger测序对GJB2(Cx26)的编码区进行突变分析。结果:4例患者均具有角膜炎-鱼鳞病-耳聋综合征的系统特征。每个患者都被发现有一个错义突变,导致天冬氨酸在密码子50处被天冬酰胺取代(p.D50N)。主要的眼科特征是血管化角膜病变、眼表疾病、角化过度的眼睑病变、复发性上皮缺陷和角膜基质瘢痕形成。一名患者进行了多次手术,包括浅表角膜切除术和板层角膜移植术,但未能预防严重的视力损失。相反,酮康唑口服治疗稳定了另外两名角膜炎-鱼鳞病-耳聋综合征患者的角膜和皮肤病。接受贝伐单抗角膜内注射的患者在单次应用后角膜血管形成明显减少。结论:角膜炎-鱼鳞病-耳聋综合征是一种罕见的外胚层发育不良,由GJB2(Cx26)杂合突变引起,伴有严重的进行性血管化角膜病变。口服酮康唑治疗可能有助于稳定角膜和皮肤病。
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来源期刊
Ophthalmic Genetics
Ophthalmic Genetics 医学-眼科学
CiteScore
2.40
自引率
8.30%
发文量
126
审稿时长
>12 weeks
期刊介绍: Ophthalmic Genetics accepts original papers, review articles and short communications on the clinical and molecular genetic aspects of ocular diseases.
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