Zeppieri Marco, Gentile Mattia, Acquaviva Antonio, Scollo Davide, D'Esposito Fabiana, Gagliano Giuseppe, Avitabile Alessandro, Gagliano Caterina, Lapenna Lucia
Department of Ophthalmology, University Hospital of Udine, 33100 Udine, Italy.
Department of Medicine, Surgery and Health Sciences, University of Trieste, 34127 Trieste, Italy.
Diagnostics (Basel). 2025 Jun 24;15(13):1596. doi: 10.3390/diagnostics15131596.
Brittle cornea syndrome (BCS) is a rare, autosomal recessive connective tissue disorder characterized by extreme corneal thinning, high myopia, and increased risk of spontaneous or trauma-induced ocular rupture. It is primarily caused by mutations in the ZNF469 or PRDM5 genes, which regulate extracellular matrix integrity. Early recognition and diagnosis of BCS are crucial to prevent severe visual impairment. This report presents two genetically confirmed cases of BCS in Albanian siblings, emphasizing the diagnostic value of whole-exome sequencing and individualized surgical management strategies. Two siblings-a 28-year-old male and a 25-year-old female-presented with progressive visual deterioration and marked corneal thinning (<200 µm). Both had a history of spontaneous ocular rupture following minor trauma in the contralateral eye. Detailed ophthalmologic evaluation revealed keratoglobus, high myopia, and irregular astigmatism. Genetic testing identified the homozygous pathogenic variant c.974delG (p.Cys325LeufsX2) in the PRDM5 gene in both cases. The male underwent penetrating keratoplasty (PKP), achieving a best-corrected visual acuity (BCVA) of 20/30. The female initially underwent deep anterior lamellar keratoplasty (DALK), which was converted to PKP intraoperatively due to central endothelial perforation, resulting in a BCVA of 20/25. Both patients remained complication-free over a 7-year follow-up period. These cases highlight the importance of early genetic diagnosis and a tailored surgical approach in managing BCS. Long-term monitoring and protective strategies are essential to prevent complications. Incorporating genetic testing into clinical practice can enhance diagnostic accuracy and guide personalized treatment plans in patients with hereditary corneal dystrophies.
脆性角膜综合征（BCS）是一种罕见的常染色体隐性结缔组织疾病，其特征为角膜极度变薄、高度近视，以及自发性或外伤诱发的眼球破裂风险增加。它主要由ZNF469或PRDM5基因的突变引起，这些基因调节细胞外基质的完整性。BCS的早期识别和诊断对于预防严重视力损害至关重要。本报告介绍了两名经基因确诊的阿尔巴尼亚同胞患BCS的病例，强调了全外显子测序的诊断价值和个体化手术管理策略。两名同胞——一名28岁男性和一名25岁女性——出现进行性视力恶化和明显的角膜变薄（<200µm）。两人均有对侧眼轻微外伤后自发性眼球破裂的病史。详细的眼科评估显示有球形角膜、高度近视和不规则散光。基因检测在两例中均确定PRDM5基因存在纯合致病性变异c.974delG（p.Cys325LeufsX2）。男性接受了穿透性角膜移植术（PKP），最佳矫正视力（BCVA）达到20/30。女性最初接受了深板层角膜移植术（DALK），术中因中央内皮穿孔转为PKP，最终BCVA为20/25。在7年的随访期内，两名患者均未出现并发症。这些病例凸显了早期基因诊断和针对BCS的定制手术方法的重要性。长期监测和保护策略对于预防并发症至关重要。将基因检测纳入临床实践可提高遗传性角膜营养不良患者的诊断准确性并指导个性化治疗方案。
