Band-shaped keratopathy in HNF4A-related Fanconi syndrome: a case report and review of the literature

ABSTRACT

Background

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.

Material and Methods

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.

Results

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.

Conclusions

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.

KEYWORDS:

• Fanconi Syndrome (FS)
• genetic analysis
• HNF4A
• Band-Shaped Keratopathy (BSK)
• Type 2 renal tubular acidosis (Type-2 RTA)

Acknowledgments

This manuscript was prepared under a collaborative agreement between the LV Prasad Eye Institute, Hyderabad, India, and the University of Illinois Eye and Ear Infirmary, Chicago. The authors would like to express their gratitude to Prof. Deepak Edward for providing valuable histological insights and expertise in correlating the findings with the clinical data. Special thanks are extended to Sreedhar Rao and Chenchu Naidu from the Ocular Pathology Services at L.V. Prasad Eye Institute, for their assistance in the laboratory work conducted for this study.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Authorship

All authors attest that they meet the current ICMJE criteria for Authorship.

Contributorship statement

Involved in design and conduct of the study (MDR, AV);

Data collection (AP, AV, MDR);

Analysis and interpretation of results (AV, AP, MDR);

Preparation of manuscript and literature search (AV, AP, MDR, DE);

Review of the manuscript (MDR, DE, DKM);

Final approval (MDR).

Patient consent

Consent to publish this case report has been obtained from the patient(s) in writing. This report does not contain any personally identifying information.

Additional information

Funding

This study was supported by the Hyderabad Eye Research Foundation and Hyderabad Eye Institute, Hyderabad, India.