Original ArticleFatal Familial Infantile MyelofibrosisSheikha, Anwar MD, FRCP, FRCPath., FACP Author Information From the Department of Hematology, College of Medicine, King Khalid University, Abha, Saudi Arabia. Received for publication June 3, 2003; accepted September 2, 2003. Published in Blood in abstract form and presented at the 40th annual meeting of the American Society of Hematology, Miami Beach, Florida, Dec. 4, 1998 (Blood. 1998;92:256b [Supplement 1], Abstract 4105). Reprints: Anwar Sheikha, MD, FRCP, FRCPath, FACP, Senior Consultant Clinical Hematologist, King Khalid University Medical College, Abha, P.O. Box 641, Saudi Arabia (e-mail: [email protected]). Journal of Pediatric Hematology/Oncology: March 2004 - Volume 26 - Issue 3 - p 164-168 Buy Abstract Malignant megakaryopoiesis can cause chronic or acute myelofibrosis through production of fibrogenic cytokines. Chronic myelofibrosis is a clonal disorder with marrow fibrosis, myeloid metaplasia, gross splenomegaly, and teardrop cells. Acute myelofibrosis differs by its aggressiveness, by the fact that it is more common in children, and by lack of organomegaly or anisopoikilocytosis. Surprisingly, in early childhood and infancy, splenomegaly and teardrop red cells become an important feature. Infantile myelofibrosis is a rare disease, except in Down syndrome. Familial occurrence of infantile myelofibrosis is exceedingly rare. The author describes an unfortunate family whose four consecutive children died of a very fulminant form of acute myelofibrosis during their first year of life. The fulminant nature of the disease, the degree of splenomegaly, and the prominence of anisopoikilocytosis were even more marked than in currently reported cases of infantile myelofibrosis. The mode of inheritance remained illusive. With two female children, sex-linked inheritance was not possible. It could not have been inherited in an autosomal dominant fashion with normal parents and with two normal children from the father's second marriage. A new autosomal dominant mutation in the germ cell of either parent is another possibility. Autosomal recessive inheritance remained a logical explanation, although such a high degree of disease presentation in a non-consanguineous marriage seems to put that possibility in question. © 2004 Lippincott Williams & Wilkins, Inc.