Multiple myeloma in three siblings

There have been 53 reported instances of myeloma occurring in more than one family member but in only three of these reports have three siblings been affected (Alexander & Benninghoff 1967; Maldonado & Kyle 1974; Horwitz et al. 1985; Crozes-Bony et al. 1995). We report a family where three siblings had an unequivocal diagnosis of myeloma made over a period of six years. The paraprotein isotype was IgG kappa in two of the siblings and kappa light chain only in the remaining sibling. The importance of these cases lies in the fact that they are highly suggestive of a genetic predisposition to the development of myeloma. Because of the high prevalence of p53 abnormalities in certain types of familial cancer screening for p53 mutation in exons 5-8 was performed by denaturing gradient gel electrophoresis (DGGE) on DNA extracted from the bone marrow of the three siblings. Although a p53 mutation was identified in one of the siblings it was felt to represent a somatic as opposed to a germline mutation.