CEBPA-associated familial acute myeloid leukemia mimicking Werner syndrome: a case report

<i>CEBPA</i>-associated familial acute myeloid leukemia (AML) is an autosomal dominant leukemia predisposition syndrome associated with germline variants in the <i>CEBPA</i> gene. Werner syndrome (WS) is an autosomal recessive progeroid syndrome causing premature aging and malignancies (e.g., AML). We report a 41-year-old man referred for medical genetic evaluation because of 3 synchronous tumors (colon, kidney, and thyroid) and premature aging. He underwent hematopoietic stem cell transplantation (HSCT) at 12 years of age because of AML diagnosed 3 years earlier. His sister (donor for the HSCT) and his brother later developed AML, as did two of her sister's three children. The patient met the clinical criteria for a "probable" WS, but duo-based (urine and blood DNA) whole exome sequencing did not confirm this diagnosis. A heterozygous c.350del p.(Gly117Alafs*43) pathogenic variant in the <i>CEBPA</i> gene was found in the proband's urine and blood DNA, and in his affected relatives. We postulate that AML management led to adverse effects in the proband, mimicking a WS phenotype (phenocopy). To our knowledge, this is the first report of a leukemia predisposition syndrome mimicking a progeroid syndrome. The diagnosis allowed for personalized medicine (i.e., lifelong regular complete blood count check-up) in the proband and his affected relatives.