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Familial Waldenstrom's macroglobulinemia
1Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
Abstract:
The etiology of Waldenstrom's macroglobulinemia (WM) is unknown. A possible role for genetic factors has been suggested by reports of familial clustering of WM. However, it is not yet possible to define the proportion of all WM that occurs in the familial setting. Review of the data on the 12 families published since 1962 suggests that familial WM may differ from sporadic disease in certain respects. Among these families, there is a pronounced occurrence of a variety of immunologic abnormalities in the relatives of WM cases. Notably, the prevalence of IgM monoclonal gammopathy (IgM MG) in first-degree relatives of WM cases was reported to be as high as 6.3%, representing a 10-fold increase relative to general population estimates. IgM MG has been shown to progress to WM at a rate of approximately 1.5% per year in a large case series; whether this rate of progression is altered in familial WM is unknown. Although limited by small numbers and a lack of systematic ascertainment and evaluation, these data are intriguing and provide a compelling basis for further study and systematic investigation of WM in families.
Insights
Familial Waldenstrom
Area of Science:
- Hematology
- Oncology
- Genetics
Background:
- The exact cause of Waldenstrom's macroglobulinemia (WM) remains unknown.
- Reports of familial clustering suggest a potential genetic component in WM etiology.
- The proportion of WM cases occurring in a familial setting is not well-defined.
Purpose of the Study:
- To review existing data on familial Waldenstrom's macroglobulinemia.
- To investigate potential differences between familial and sporadic WM.
- To explore the prevalence of immunologic abnormalities in relatives of WM patients.
Main Methods:
- Review of published data on 12 families with Waldenstrom's macroglobulinemia since 1962.
- Analysis of immunologic abnormalities in first-degree relatives of WM cases.
- Comparison of IgM monoclonal gammopathy (IgM MG) prevalence in relatives versus general population.
Main Results:
- Familial WM may present distinct characteristics compared to sporadic cases.
- A significant occurrence of various immunologic abnormalities was observed in WM relatives.
- Prevalence of IgM MG in first-degree relatives was 6.3%, a tenfold increase over general population estimates.
Conclusions:
- Familial clustering and specific immunologic abnormalities suggest a genetic predisposition to WM.
- The high prevalence of IgM MG in relatives warrants further investigation due to its known progression to WM.
- Despite limitations, findings support systematic studies of WM within families.
