7468

WHSC1

MMSET|NSD2|REIIBP|TRX5|WHS;Wolf-Hirschhorn syndrome candidate 1;WHSC1;Wolf-Hirschhorn syndrome candidate 1

IL5 promoter REII region-binding protein|multiple myeloma SET domain containing protein type III|nuclear SET domain-containing protein 2|probable histone-lysine N-methyltransferase NSD2|trithorax/ash1-related protein 5

4p16.3

protein-coding

Wolf-Hirschhorn syndrome (WHS) is a rare chromosomal disorder attributable to a deletion at the short arm of chromosome 4. This syndrome is associated with characteristic facial appearance, multiple congenital abnormalities, mental retardation, feeding difficulties and failure to thrive. We report two girls with WHS who developed myelodysplastic syndrome (MDS). According to the "Category, Cytology, Cytogenetic (CCC)"classification of childhood MDS, patient 1 had refractory cytopenia with ring sideroblasts at the age of 6 years, while patient2 had refractory cytopenia with dysplasia at the age of 5-1/2 years. Patient 1 progressed to refractory cytopenia with excess blasts within a year, while patient 2 progressed to acute lymphoblastic leukemia within 1 month of presentation. It is possible that allelic loss of a tumor suppressor gene such as WHSC1 and/or FGFR3 from the deleted segment 4p16.3 plays a critical role in the process of malignant transformation. To our knowledge, this is the first report of severe hematological complications like MDS and leukemia in children with WHSand may be an important genetic model for understanding malignant hematological transformation. This report also underscores the importance of evaluating children with WHS for hematopoietic dysfunction.#CI- Copyright 2003 Wiley-Liss, Inc.