Identification of a VHL gene mutation in atypical Von Hippel-Lindau syndrome: genotype-phenotype correlation and gene therapy perspective

Background Classical von Hippel Lindau (VHL) disease/syndrome includes CNS hemangioblastoma, renal or pancreatic cysts, pheochromocytoma, renal carcinoma and exodermic cystadenoma. The syndrome is caused by mutation of VHL tumor suppressor gene. The most prevalent mutations are present in VHL syndrome. To date, > 500 mutations of gene related to the progression of VHL syndrome have been reported. VHL gene mutation presented in single lung or pancreatic tumor has been reported occasionally, but there is no report of both. Methods In this paper, we used CT scan, pathological and genetic examination methods to diagnose a rare atypical VHL syndrome. Results We reported a rare case of atypical VHL syndrome with authenticated VHL mutation at p.Arg167Gln, that was associated with not only bilateral pheochromocytoma but also lung carcinoid and neuroendocrine tumor of pancreas. Based on literature reviews, the patient was recommended to be further subjected to octreotide-based radionuclide therapy. Conclusions Combined with gene detection and clinical diagnosis, we found the inherent relationship between VHL genotype and phenotype, and constructed the standard diagnosis and treatment process of disease with rare VHL mutation from the perspective of gene therapy.

Automated summary

This study diagnosed a rare atypical VHL syndrome using CT scan, pathological and genetic examination methods. The patient had a confirmed VHL mutation associated with bilateral pheochromocytoma, lung carcinoid, and pancreatic neuroendocrine tumor. Based on literature reviews, octreotide-based radionuclide therapy was recommended for the patient, highlighting the relationship between VHL genotype and phenotype.