The clinical and screening age-at-onset distribution for the MEN-2 syndrome

• Published in: American journal of human genetics Vol. 44; no. 2; pp. 208 - 215
• Main Authors: EASTON, D. F, PONDER, M. A, CUMMINGS, T, GAGEL, R. F, HANSEN, H. H, REICHLIN, S, TASHJIAN, A. H. JR, TELENIUS-BERG, M, PONDER, B. A. J
• Format: Journal Article
• Language: English
• Published: Chicago, IL University of Chicago Press 01.02.1989
• Subjects: Adrenal Gland Neoplasms - epidemiology; Adrenal Gland Neoplasms - genetics; Adult; Age Factors; Aged; Biological and medical sciences; Endocrinopathies; Female; General aspects. Associated endocrine diseases. Endocrine paraneoplasic syndromes; Genetic Testing; Humans; Male; Medical sciences; Middle Aged; Models, Genetic; Multiple Endocrine Neoplasia - epidemiology; Multiple Endocrine Neoplasia - genetics; Pheochromocytoma - epidemiology; Pheochromocytoma - genetics; Probability; Human; Heterozygozity; Probability law; Pheochromocytoma; Family study; Estimation; Sex; Thyroid gland; Screening test; Statistical study; Multiple endocrine neoplasia type II; Incidence; Screening; Age of onset; Gene penetrance; Medullary carcinoma; Multiple endocrinopathy; Tumor
• ISSN: 0002-9297; 1537-6605

The decision to screen for multiple endocrine neoplasia type 2 (MEN-2) is generally based on family history, the rationale for this approach being the presumed 100% penetrance of the disease. To determine the validity of this presumption we have estimated--by applying modifications of the life-table method--the clinical and screening age-at-diagnosis distributions for MEN-2, using families from the Cancer Research Campaign Medullary Thyroid Cancer Register and one large American family. The clinical penetrance of MEN-2 is shown to be incomplete, an estimated 41% of gene carriers not presenting with symptoms by age 70 on the basis of clinical history. Screening by the standard tests for detecting the earliest manifestations of the syndrome increases the penetrance to an estimated 93% by age 31. There is no evidence of a difference in the age-at-diagnosis distributions between maternal and paternal transmission, or among different families, but there is some suggestion of an earlier onset of medullary thyroid cancer in female gene carriers, and of a tendency of pheochromocytoma to cluster in families. These results can be used to calculate risks to relatives of affected individuals, which in turn can be used to guide decisions on which individuals to screen.