Familial multiple myeloma represents approximately 1-2% of all MM cases, characterized by the occurrence of MM in two or more first-degree relatives. While the exact genetic mechanisms remain unclear, several familial clustering studies suggest inherited susceptibility genes and shared environmental factors. Immunosuppression following solid organ transplantation may accelerate malignant transformation in genetically predisposed individuals, creating a unique clinical scenario requiring specialized monitoring and management approaches.

A 50-year-old female with a complex medical history presented with fatigue, weakness, and anemia. Her medical background included type 1 diabetes mellitus diagnosed in 1982 at age 8, progression to end-stage renal disease secondary to diabetic nephropathy in 2001, and successful deceased donor kidney transplantation in 2007. She remained on chronic immunosuppressive therapy with mycophenolic acid (Myfortic®) and cyclosporine (Sandimmun®) with stable graft function.

The patient's family history was remarkable for multiple myeloma: her mother was alive with confirmed MM diagnosis, and her brother had previously died from MM after receiving treatment. This strong familial clustering placed her in the high-risk category for hereditary MM predisposition.

Physical examination revealed pallor consistent with anemia, but no lymphadenopathy, bone tenderness, or other significant findings. Laboratory evaluation demonstrated significant anemia (hemoglobin 7.8 g/dL, hematocrit 26.2%) with normocytic indices (MCV 87 fL). Renal function remained stable post-transplant, and serum calcium was within normal limits.

Protein studies revealed elevated beta-2 fraction on serum protein electrophoresis with positive IgG-kappa monoclonal band on immunofixation electrophoresis. Free light chain analysis showed elevated kappa (40.7 mg/L) with kappa/lambda ratio of 1.86.

Bone marrow examination demonstrated 3-4% plasma cells with flow cytometry confirming CD138+/CD38+ phenotype and kappa light chain restriction (80% kappa, 20% lambda), establishing clonality. Comprehensive FISH analysis was negative for high-risk cytogenetic abnormalities including p53 deletion, del(13q), t(11;14), and t(4;14).

Lumbar MRI revealed disc protrusions without lytic bone lesions. Genetic analysis for FMF mutations was performed given potential inflammatory contributions, showing R202Q heterozygosity and other polymorphisms without pathogenic significance.

Based on the presence of IgG-kappa monoclonal protein, 3-4% clonal bone marrow plasma cells, anemia, and absence of hypercalcemia or lytic lesions, the patient was diagnosed with smoldering multiple myeloma.

This case illustrates several important aspects of familial MM. The strong family history with both maternal and sibling involvement suggests significant genetic predisposition, warranting enhanced surveillance protocols. The co-existence of chronic immunosuppression following renal transplantation creates additional complexity, as immunosuppressive agents may accelerate progression from precursor states to overt malignancy.