Bilateral pheochromocytomas and congenital anomalies associated with a de novo germline mutation in the von Hippel-Lindau gene.

A 12-year-old boy presented with severe hypertension, congenital microcephaly, severe hearing loss, developmental delay, cryptorchidism, and bilateral pheochromocytomas, without the phenotypic features of multiple endocrine neoplasia type II syndromes (MEN-2). Sequence analysis of the polymerase chain reaction (PCR)-amplified gnomic DNA identified a missense mutation at nucleotide 451 of the von Hippel-Lindau (VHL) gene (A451G) that changes a codon for serine (AGT) to one for glycine (GGT) at amino acid position 80 (S80G). The sequence DNA analysis of the parents did not show a mutation in the VHL gene that was previously identified in their affected son. The observed constellation of microcephaly, deafness, cryptorchidism, developmental delay, hypertension, and bilateral pheochromocytoma in association with a VHL mutation A451G in a patient with negative family history has not previously been described in the literature. Knowledge that VHL mutation plays a critical role in sporadic pheochromocytoma should aid in the future diagnosis and treatment of this tumor. Genetic testing in known pheochromocytoma families is indicated to identify genetically abnormal subjects that carry the MEN-2, VHL, and glomus tumor gene mutations.