The Veneto Eye Bank Foundation, Venice, Italy.
Ophthalmology. 2012 Jan;119(1):74-83. doi: 10.1016/j.ophtha.2011.06.044. Epub 2011 Sep 28.
To describe the ocular phenotype in patients with ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome (MIM#604292) and to determine the pathogenic basis of visual morbidity.
Retrospective case series.
Nineteen families (23 patients) affected by EEC syndrome from the United Kingdom, Ireland, and Italy.
General medical examination to fulfill the diagnostic criteria for EEC syndrome and determine the phenotypic severity. Mutational analysis of p63 was performed by polymerase chain reaction-based bidirectional Sanger sequencing. All patients with EEC syndrome underwent a complete ophthalmic examination and ocular surface assessment. Limbal stem cell deficiency (LSCD) was diagnosed clinically on the basis of corneal conjunctivalization and anatomy of the limbal palisades of Vogt. Impression cytology using immunofluorescent antibodies was performed in 1 individual. Histologic and immunohistochemical analyses were performed on a corneal button and corneal pannus from 2 EEC patients.
The EEC syndrome phenotypic severity (EEC score), best-corrected Snellen visual acuity (decimal fraction), slit-lamp biomicroscopy, tear function index, tear breakup time, LSCD, p63 DNA sequence variants, impression cytology, and corneal histopathology.
Eleven heterozygous missense mutations in the DNA binding domain of p63 were identified in all patients with EEC syndrome. All patients had ocular involvement and the commonest was an anomaly of the meibomian glands and lacrimal drainage system defects. The major cause of visual morbidity was progressive LSCD, which was detected in 61% (14/23). Limbal stem cell deficiency was related to advancing age and caused a progressive keratopathy, resulting in a dense vascularized corneal pannus, and eventually leading to visual impairment. Histologic analysis and impression cytology confirmed LSCD.
Heterozygous p63 mutations cause the EEC syndrome and result in visual impairment owing to progressive LSCD. There was no relationship of limbal stem cell failure with the severity of EEC syndrome, as classified by the EEC score, or the underlying molecular defect in p63.
FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any of the materials discussed in this article.
描述先天性外胚层发育不良-外胚层-面裂（EEC）综合征（MIM#604292）患者的眼部表型，并确定致盲的发病基础。
回顾性病例系列研究。
来自英国、爱尔兰和意大利的 19 个 EEC 综合征家族（23 例患者）。
进行全面的医学检查，以满足 EEC 综合征的诊断标准并确定表型严重程度。通过聚合酶链反应双向 Sanger 测序进行 p63 的突变分析。所有 EEC 综合征患者均接受全面的眼科检查和眼表评估。基于角膜结膜化和 Vogt 角膜缘栅栏的解剖结构，临床诊断为角膜缘干细胞缺乏症（LSCD）。对 1 例个体进行免疫荧光抗体的印迹细胞学检查。对 2 例 EEC 患者的角膜活检和角膜血管翳进行组织学和免疫组织化学分析。
EEC 综合征表型严重程度（EEC 评分）、最佳矫正视力（十进制分数）、裂隙灯生物显微镜检查、泪液功能指数、泪膜破裂时间、LSCD、p63 DNA 序列变异、印迹细胞学和角膜组织病理学。
在所有 EEC 综合征患者中均发现了 p63 DNA 结合域的 11 个杂合错义突变。所有患者均存在眼部受累，最常见的是睑板腺和泪液引流系统异常。视力受损的主要原因是进行性 LSCD，在 23 例患者中有 61%（14/23）存在 LSCD。LSCD 与年龄增长有关，导致进行性角膜病变，导致致密的血管化角膜血管翳，最终导致视力损害。组织学分析和印迹细胞学证实了 LSCD。
杂合 p63 突变导致 EEC 综合征，并因进行性 LSCD 导致视力损害。LSCD 与 EEC 评分所分类的 EEC 综合征严重程度或 p63 中的潜在分子缺陷之间没有关系。
作者在本文讨论的任何材料中均没有自有或商业利益。
