PHEOCHROMOCYTOMA IN VON-HIPPEL-LINDAU-DISEASE - CLINICAL PRESENTATIONAND MUTATION ANALYSIS IN A LARGE, MULTIGENERATIONAL KINDRED

The clinical presentation and characterization of the mutation in memb ers of a large kindred with von Hippel-Lindau disease (VHLD) and pheoc hromocytoma 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 definiti ve diagnosis and treatment of pheochromocytoma occurred at 19.9 +/- 2. 6 yr. Significantly higher urine catecholamine concentrations were obs erved in younger patients than in older ones. Mutation analysis was pe rformed 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 t hat results in the substitution of a serine for an alanine residue at position 149 of the polypeptide chain. Seven of the 11 patients with t he mutation have VHLD; four, all 10 yr old or less, are asymptomatic a nd have no evidence of disease, but are at high risk for developing VH LD. These children are being followed closely for clinical and biochem ical manifestations. The characterization of this new mutation has per mitted identification of family members who are likely to develop VHLD .