Emberger syndrome, related to GATA2germline mutation, is characterized by primary lymphedema and predisposition to myelodysplasia/acute myeloid leukemia (MDS/AML).
We describe the history of 2 Emberger patients with very different evolution overtime.
The first patient, a 15-year-old girl, presented with lymphedema of the right lower limb lasting for 3 months. The initial workup revealed anemia (hemoglobin 6g/dl) and leucopenia (WBC 2,54 x109/L) with 6,5% blasts in the peripheral blood. AML with clonal monosomy 7 was diagnosed and heterozygous germline GATA2 mutation (c.954_970 del;p.Cys319Aspfs*59) was identified. Surprisingly, lymphedema regressed rapidly after initiation of chemotherapy. Despite related allogenic stem cell transplant, the patient relapsed and displayed concomitantly a resurgence of lymphedema. An unrelated transplant allowed transient AML remission and improved lymphedema but a second relapse led to the patient death after 28 months.
The second patient was 3-year-old when referred for severe progressive bilateral lymphedema of the legs. Subsequently, she developed recurrent infections including meningococcemia, genital warts, auto-immune anemia and hypothyroidism. A combine immunodeficiency with immunoglobulin, partial phagocytic, and transient complement deficiencies was demonstrated. Genetic analysis confirmed an heterozygous c.1186C>T;p.Arg396Trp GATA2 mutation. The patient has been on continuous immunoglobulin substitution for 26 years without developing MDS/AML.
This is the first report of a chronological relation between lymphedema and AML in Emberger syndrome although it was not supported by our second observation. Factors such as type of mutation, inflammation, blood viscosity and additional genetic event should be further investigated to determine the potential interactions between both disorders.