Chromosome 20 deletion in multiple endocrine neoplasia type 2: expanded double-blind studies

Multiple endocrine neoplasia (MEN) type 2A and 2B are autosomal dominant syndromes in which medullary thyroid cancers are associated with adrenal pheochromocytomas. We have expanded our double-blind studies of high-resolution G-banded chromosomes from lymphocytes to a total of 12 MEN-2A families, 7 MEN-2B (mucosal neuroma phenotype) families and 23 non-MEN control subjects. Eighteen of 23 different control subjects were scored as having normal chromosomes 20, and 15 of 21 MEN-2A and 4 of 8 MEN-2B patients were scored as having an interstitial deletion: del(20) (p12.2p12.2). These findings suggest that the dominant mutation in many MEN-2A and MEN-2B families is a visible deletion within band 20p12.2. Combining the results of these double-blind studies with those of the only other comparable reported double-blind series provides a statistical probability of less than 1/1000 that the association between MEN-2A and the deletion was observed by chance alone. However, the occasional discrepancies in classification using presently available techniques preclude the use of high resolution chromosome studies for the diagnosis of MEN-2.