Novel Case of Bilateral Adrenal Tumors Confirms Pathogenicity of Previously Described c.463+4C>G Variant in the von-Hippel Lindau Gene

TL;DR

A patient with adrenal tumors and a rare VHL gene mutation confirms the mutation's role in disease, even without family history.

Contribution

This case confirms the pathogenicity of the c.463+4C>G variant in the VHL gene in a patient with bilateral adrenal tumors.

Findings

The c.463+4C>G variant in the VHL gene was confirmed as pathogenic using next-generation sequencing and RNA analysis.

The patient had bilateral adrenal tumors, including a pheochromocytoma, with no family history of VHL-associated tumors.

The mutation may have reduced penetrance, as indicated by the lack of family history in the proband.

Abstract

We report a case of a pathogenic variant c.463+4C>G in the von Hippel-Lindau (VHL) gene identified in a patient presenting with bilateral adrenal tumors, including a histologically confirmed pheochromocytoma with no significant family history of VHL-associated tumors. This same variant was first reported as having pathogenic significance in an unrelated proband with a hemangioblastoma and a family history of pheochromocytoma. In our patient, next-generation sequencing and subsequent RNA (ribonucleic acid) analysis confirmed this mutation to be a pathogenic (class 4) variant in intron 2. The lack of family history of VHL-associated tumors correlated with the proband further suggests that this mutation may have reduced penetrance. This case confirms the pathogenicity of the same previously described variant in the VHL gene and underscores the utility of genetic testing in patients with atypical presentations of adrenal tumors, even in the absence of a relevant family history.