CLINICAL CHARACTERISTICS OF HEREDITARY PANCREATITIS IN A LARGE FAMILY, BASED ON HIGH-RISK HAPLOTYPE

Objectives: Because there are no markers for hereditary pancreatitis ( HP), diagnosis has relied on clinical features and inferences. Identif ication of the HP disease gene locus on chromosome 7q35 provides the f irst genetic marker for HP, allowing an accurate comparison of the cli nical diagnosis of HP with the presence of a high-risk HP haplotype. O ur objectives were to compare the clinical diagnosis of HP with inheri tance of the HP gene and to characterize the common clinical features. Methods: A detailed questionnaire was administered to 102 study parti cipants of a large HP kindred. Blood samples were taken for DNA extrac tion and high-risk haplotype determination. Clinical findings were com pared with the presence of a high-risk haplotype. Results: A family tr ee of more than 500 members and eight generations was constructed, and clinical features of the 102 participants were determined. HP occurre d before the age of 5 yr in 58% of subjects, who presented with common symptoms of abdominal pain, nausea/vomiting, and frequent attacks. Th irty-five probands, of whom 80% had clinical symptoms, carried the hig h-risk haplotype, confirming previous estimates of 80% penetrance. Thi rty-two of the study participants had been clinically diagnosed with H P, whereas 70 were clinically unaffected. With regard to the presence of the high-risk haplotype, 87.5% of the clinically diagnosed patients were affected by HP (true positive), whereas 12.5% did not carry the high-risk haplotype (false positive). Seven obligate carriers were ide ntified through DNA analysis; three had previously been unrecognized b ecause of lack of affected offspring. Conclusions: The diagnosis of he reditary pancreatitis on clinical grounds alone may be inaccurate in l ess severe cases, as is the exclusion of carrier status through family tree analysis. Therefore, a definitive diagnosis of hereditary pancre atitis in equivocal cases or exclusion of a carrier state should inclu de analysis of genetic markers.