FAMILIAL PARAGANGLIOMAS - LINKAGE TO CHROMOSOME 11Q23 AND CLINICAL IMPLICATIONS

Familial paragangliomas (PGL), or glomus tumors, are slow-growing, hig hly vascular, generally benign neoplasms usually of the head and neck that arise from neural crest cells. This rare autosomal-dominant disor der is highly penetrant and influenced by genomic imprinting through p aternal transmission, Timely detection of these tumors affords the aff ected individual the opportunity to avoid the potential morbidity asso ciated with surgical removal, and mortality that may accompany local a nd distant metastases, Linkage to two distinct chromosomal loci, 11q13 .1 and 11q22.3-q23, has been reported, suggesting heterogeneity, We ev aluated three multigenerational families with hereditary PGL, includin g 19 affected, and 59 unaffected and potentially at-risk individuals, Numerous microsatellite markers corresponding to each candidate region were tested in all members of the three families. Confirmation of lin kage to 11q23 was established in all three families, The inheritance p attern was consistent with genetic imprinting, Using these data, we we re able to provide presymptomatic diagnosis with subsequent removal of tumor from one individual, and to start several others on an MRI surv eillance protocol. (C) 1997 Wiley-Liss, Inc.