Kallam Anji Reddy Molecular Genetics Laboratory, Brien Holden Eye Research Centre, L V Prasad Eye Institute, Hyderabad, India.
Institute for Rare Eye Diseases and Ocular Genetics, L V Prasad Eye Institute, Hyderabad, India.
Ophthalmic Genet. 2024 Jun;45(3):246-251. doi: 10.1080/13816810.2023.2285310. Epub 2023 Nov 24.
Fanconi's syndrome (FS) is characterized by type-2 renal tubular acidosis, short stature, and renal rickets, along with glycosuria, aminoaciduria, hypophosphaturia, and urinary bicarbonate wasting. The genetic form of FS has been linked to HNF4A variants. Although additional clinical features such as hearing impairment have recently been associated with HNF4A-linked FS, its ocular manifestation has not been described.
Presenting a case of a 5-year-old male child with bilateral progressive corneal opacification and the presence of bilateral greyish-white deposits in the interpalpebral region since infancy. A next-generation sequencing (NGS)-based genetic testing was performed for the child followed by parental genetic testing for the identified variant. Furthermore, relevant works of literature were reviewed related to this condition.
Detailed corneal findings showed a bilateral band-shaped keratopathy (BSK) in the patient. Physical and systemic findings showed signs consistent with FS. Sequencing analysis revealed a novel heterozygous c.635C>T, (p.Pro212Leu) variant in the HNF4A gene in the proband and mother, while the father had a normal genotype.
Our case highlights the occurrence of BSK in an exceptionally rare manifestation of hereditary FS linked to HNF4A gene variant. The variant exists both in proband and asymptomatic mother. Therefore, the variable penetrance which is known to exist in HNF4A is acknowledged in this context. This report suggests the first documented instance establishing a plausible connection between BSK and HNF4A-associated FS, characterized by the variable penetrance attributed to the HNF4A gene.
范可尼综合征（FS）的特征是 2 型肾小管酸中毒、身材矮小和肾性佝偻病，同时伴有糖尿、氨基酸尿、低磷血症和尿碳酸氢盐排泄。FS 的遗传形式与 HNF4A 变异有关。尽管最近发现 HNF4A 相关 FS 还伴有听力损伤等其他临床特征，但尚未描述其眼部表现。
我们报告了一名 5 岁男童的病例，该男童自出生以来双眼逐渐出现角膜混浊，并在双眉弓之间存在灰白色沉积。对患儿进行了基于下一代测序（NGS）的基因检测，并对父母进行了针对所识别变异的基因检测。此外，还对与该疾病相关的文献进行了回顾。
详细的角膜检查结果显示患者存在双侧带状角膜病变（BSK）。体格检查和系统检查结果显示符合 FS 的体征。测序分析显示在患儿和母亲的 HNF4A 基因中发现了一个新的杂合 c.635C>T，（p.Pro212Leu）变异，而父亲的基因型正常。
我们的病例突出了 BSK 在与 HNF4A 基因突变相关的遗传性 FS 非常罕见的表现中的发生。该变异存在于患儿和无症状的母亲中。因此，在这种情况下，HNF4A 已知存在的可变外显率得到了认可。本报告首次记录了 BSK 与 HNF4A 相关 FS 之间的可能联系，其特征是归因于 HNF4A 基因的可变外显率。
