Endocrine Abstracts

Background: Von Hippel-Lindau disease (VHL) is an autosomal dominant disease, characterized by haemangioblastomas of the retina and CNS, renal cell carcinomas (RCC) and renal cysts, pheochromocytomas, pancreatic neuroendocrine tumors and cysts, and endolymphatic sac tumors. VHL is associated with a germline mutation of the VHL tumor suppressor gene on the short arm of chromosome 3. The type-1 disease is caused by mutations, leading to severe disruption of protein activity, including deletions, missense and nonsense mutations, and other microdeletions/insertions. However, the type-2 disease is generally associated with missense mutations in approximately 96% of the cases. Herein, we report a family with pheochromocytomas in 3 generations and 4 affected members. The family had recurrent pheochromocytomas with retinal angiomas and spinal cord hemangioblastomas. However, none of the family members had RCC. A novel heterozygous class-2 mutation in exon3 of VHL gene (c.572_574delACC/p.His191del) was determined by DNA sequence analysis in all affected family members.

Cases: The first case is a 63 years old female who had been operated for bilateral pheochromocytomas when she was 38. MRI of the spinal cord demonstrated a 19×68 mm hemangioblastoma at the T12-L1 vertebra levels. The second case is a 38 years old female who had been operated for bilateral pheochromocytomas when she was 16. Ophthalmological examination demonstrated an optic nerve and a peripheral angioma. Abdominal and spinal cord MRI demonstrated a 14×6 mm hemangioblastoma at the T12-L1 vertebra levels and a 45×35 mm broad ligament cyst. The third case is a 42 years old male who had been operated for bilateral pheochromocytomas when he was 22. An asymptomatic recurrent 3.5×14 mm right adrenal pheochromocytoma was diagnosed by high plasma normetanephrine and serum chromogranin A levels and confirmed by abdominal MRI and GA-68 DOTATATE PET/CT. The fourth case is a 17 years old male, who had been operated for bilateral pheochromocytomas when he was 9. He admitted for hypertension 9 months before. His plasma normetanephrine, and serum chromogranin A level was high. A 2×15 mm mass at the right adrenal area was determined by MRI and GA-68 DOTATATE PET/CT. Ophthalmological examination demonstrated a peripheral retinal angioma.

Conclusions: In this family, we found a novel class-2 heterozygous mutation in the VHL gene in all family members, that has not previously been reported. This mutation leads to the development of recurrent bilateral pheochromocytomas at a very young age, spinal hemangioblastomas, and retinal angiomas, but probably doesn’t lead to RCC.