Ann Hematol (2003) 82:223–227 DOI 10.1007/s00277-003-0614-4 ORIGINAL ARTICLE A. Deviren · N. Yalman · S. Hacihanefioglu Differential diagnosis of Fanconi anemia by nitrogen mustard and diepoxybutane Received: 3 September 2002 / Accepted: 4 January 2003 / Published online: 1 March 2003  Springer-Verlag 2003 Abstract Fanconi anemia (FA) is an autosomal recessive inherited disorder which is associated with a variety of congenital anomalies. These include morphometric ab- normalities involving mainly the head and face, skeletal malformations particularly of the radial ray, growth retardation, abnormal skin pigmentation, deafness, and renal, ocular, genital, and cardiac defects. The cardinal clinical feature is a severe progressive pancytopenia. The overall aim of our study was to compare two different alkylating agents that would permit rapid and unequivocal detection of FA. A total of 271 patients underwent nitrogen mustard (NTM) and diepoxybutane (DEB) tests in our laboratory; baseline chromosomal breakage was studied for all of them. After the results of the chromo- somal breakage studies, 72 patients were diagnosed as affected and 136 patients as unaffected by FA. We also studied 63 family members of FA patients. According to our study, NTM seems more specific to identify chro- mosomal breakages in FA parents than DEB. Keywords Fanconi anemia · Chromosome breakage · Nitrogen mustard · Diepoxybutane Introduction The Fanconi anemia syndrome (FA) was originally described by Guido Fanconi in 1927. In his report, he described three brothers with a condition resembling pernicious anemia. Evidently the anemia was the main symptom of the disease [2, 11]. Fanconi anemia is an autosomal recessive inherited disorder, which is associ- ated with a variety of congenital anomalies. These include morphometric abnormalities involving mainly the head and face, skeletal malformations particularly of the radial ray, growth retardation, abnormal skin pigmentation, deafness, and renal, ocular, genital, and cardiac defects. The cardinal clinical feature, however, is a severe, progressive pancytopenia, with a mean age of onset at 7–8 years, with death generally occurring within 5 years. The development of acute nonlymphoblastic leukemia is a common occurrence [5, 30]. Phenotypic diversity makes diagnosis difficult in patients who manifest few or no clinical features of FA other than bone marrow insuffi- ciency. The significant increase in spontaneous chromo- some breakage found in cultured peripheral blood lymphocytes and dermal fibroblasts from FA patients compared with that found in cells from normal individuals has been used to confirm the diagnosis in those patients. However, other patients with clinical features of FA have been reported not to manifest increased chromosome breakage [5]. In addition, longitudinal studies of chro- mosome instability in FA patients showed a wide variation in the frequency of baseline breakage within the same individual, ranging from no baseline breakage to high levels [6]. Thus, the study of spontaneous chromo- some breakage, in addition to being laborious and time consuming, is not reliable in the diagnosis of FA [5]. Almost all FA cells show a specific susceptibility to the induction of chromosomal aberrations by crosslinking agents. This sensitivity is well documented and reported for mitomycin C (MMC), nitrogen mustard (NTM), diepoxybutane (DEB), 8-methoxypsoralen plus near-UV light, cyclophosphamide, cis-diamminedichloroplatinum II (cis-ptII), and X-irradiation [2, 4, 7, 9, 12, 13, 14, 19, A. Deviren ( ) ) · S. Hacihanefioglu Istanbul University, Cerrahpasa Medical Faculty, Biomedical Sciences Division, Genetics Department, Baharlibahce Sokak Kibris Apt. No:17 Daire:14, 34740 Bakirkoy-Istanbul, Turkey e-mail: devirena@istanbul.edu.tr Tel.: +90-212-5833127 Fax: +90-212-5299433 N. Yalman Istanbul University, Istanbul Medical Faculty, Pediatric Hematology Department, Istanbul, Turkey A. Deviren · S. Hacihanefioglu Istanbul University, Genetic and Teratology Research Center, Istanbul, Turkey