(BMJ)—A 23-yo man w/ short stature, congenital malformations of L thumb and both ears and a single kidney presented w/ back pain, SOB, fatigue, and easy bruising. Family hx: Brother w/ worse malformations died in early childhood. Labs: pancytopenia. What is the dx?
Shwachman-Diamond syndrome
Radioulnar synostosis w/ amegakaryocytic thrombocytopenia
Thrombocytopenia-absent radius syndrome
Dyskeratosis congenita
Fanconi anemia
You are correct. Aplastic anemia, in combination w/ thumb and radial anomalies, is typical of Fanconi anemia. Ear abnormalities affect 1 in 5 people w/ the dz, although 1 in 3 affected individuals have no deformity. Fanconi anemia increases the risk of developing myelodysplasia and acute myeloid leukemia (AML) in preteenage years and young adulthood. Because the pt’s back pain and other sx were suggestive of AML, a bone marrow aspirate was done, which showed myelodysplasia w/ 23% blasts and complex cytogenetic abnormalities. Chromosome breakage test coupled w/ gene sequencing confirmed Fanconi anemia. His pain was caused by myelodysplasia evolving into AML. He died from progressive dz before potentially life-saving hematopoietic stem cell transplant could be pursued.

BMJ 2018;363:k4528