Pheochromocytoma in von Hippel-Lindau disease : Clinical presentation and mutation analysis in a large, multigenerational kindred

• Published in: The journal of clinical endocrinology and metabolism Vol. 83; no. 1; pp. 117 - 120
• Main Authors: ATUK, N. O, STOLLE, C, OWEN, J. A, CARPENTER, J. T, VANCE, M. L
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 1998
• Subjects: Adenoma - epidemiology; Adenoma - genetics; Adolescent; Adrenal Gland Neoplasms - diagnosis; Adrenal Gland Neoplasms - epidemiology; Adrenal Gland Neoplasms - genetics; Adrenal Gland Neoplasms - therapy; Adult; Age of Onset; Aged; Biological and medical sciences; Carcinoma, Renal Cell - epidemiology; Carcinoma, Renal Cell - genetics; Catecholamines - urine; Child; Child, Preschool; Complex syndromes; Female; Hemangioma - epidemiology; Hemangioma - genetics; Humans; Infant; Kidney Neoplasms - epidemiology; Kidney Neoplasms - genetics; Male; Medical genetics; Medical sciences; Middle Aged; Pancreatic Neoplasms - epidemiology; Pancreatic Neoplasms - genetics; Pedigree; Phenotype; Pheochromocytoma - diagnosis; Pheochromocytoma - epidemiology; Pheochromocytoma - genetics; Pheochromocytoma - therapy; Point Mutation; Retinal Neoplasms - epidemiology; Retinal Neoplasms - genetics; Risk Factors; Sensitivity and Specificity; von Hippel-Lindau Disease - complications; von Hippel-Lindau Disease - genetics; Endocrinopathy; Human; Nervous system diseases; Correlation; Pheochromocytoma; Phacomatosis; Nucleotide sequence; Family study; Multigeneration study; Cardiovascular disease; Genetic determinism; Genetic disease; Secretory tumor; Vascular disease; Symptomatology; Eye disease; Central nervous system disease; Diagnosis; Mutation; Von Hippel Lindau disease
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.83.1.117

The clinical presentation and characterization of the mutation in members of a large kindred with von Hippel-Lindau disease (VHLD) and pheochromocytoma were examined. Twenty-five proven cases of VHLD occurring in four generations of a large kindred have been followed since 1964, and pheochromocytoma has occurred in 17. Symptoms of pheochromocytoma developed at an early age, on average at 12.5 +/- 1.3 yr, and definitive diagnosis and treatment of pheochromocytoma occurred at 19.9 +/- 2.6 yr. Significantly higher urine catecholamine concentrations were observed in younger patients than in older ones. Mutation analysis was performed in 14 family members, and a new mutation in the VHLD gene was identified in 11; this mutation is a G to T change at nucleotide 658 that results in the substitution of a serine for an alanine residue at position 149 of the polypeptide chain. Seven of the 11 patients with the mutation have VHLD; four, all 10 yr old or less, are asymptomatic and have no evidence of disease, but are at high risk for developing VHLD. These children are being followed closely for clinical and biochemical manifestations. The characterization of this new mutation has permitted identification of family members who are likely to develop VHLD.