الفهرس 
Subjects and MethodsOnly 14 pages are availabe for public view
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Abstract
Introduction: Fanconi anemia is an autosomal recessive disorder. It can be classified into 11 complementation groups (AL). It is characterized by bone marrow failure which leads to aplastic anemia and multiple congenital anomalies such as growth retardation, thumb, radial, renal and skin pigmentation abnormalities. About one third of cases of FA are not associated with congenital anomalies. FA is one of the cancer prone disorders that is characterized by chromosomal instability. This instability is represented by increased incidence of spontaneous and induced chromosomal breakage. It was agreed by International Fanconi Anemia Registry to use DEB as a diagnostic test for FA, but because of the powerful carcinogenic effect of DEB, many laboratories preferred the use of MMC as a diagnostic test for FA, as it is less hazardous in handling. Aim of the work: This study aims to study the variable congenital anomalies found in cases of congenital aplastic anemia. It also aims to study the chromosomal instability in the cases of congenital aplastic anemia whether they are associated with congenital anomalies or not. It aims also to compare the effect of DEB, MMC and radiation with different doses on chromosomal breakage. In addition, it aims to correlate the chromosomal breakage findings with the clinical presentation. Methods: This study included 30 individuals. 20 of them were patients with congenital aplastic anemia (10 patients with congenital anomalies named group 1 & 10 patients without congenital anomalies named group 2). The remaining 10 individuals were taken as a control group. All patients and control will be subjected to thorough history including family history, general examination to role out any congenital anomaly, a study of chromosomal instability that may occur spontaneously, after addition of diepoxybutane (DEB), mitomycin C (MMC), and after exposure of the lymphocytes of the patient to gradually increasing rads of irradiation. Results: In patients of group 1, consanguinity was positive in 70% of cases. Family history was positive in 90% of cases. Male : female ratio was 1 : 1. The clinical manifestations of these patients were hugely variable. Skin pigmentation and renal anomalies were both the most common anomalies found in 70% of cases. Skeletal anomalies in the form of radial and thumb anomalies were the second most common anomalies (60% of cases). Limb anomalies other than thumb and radius were found in 20%. However, eye anomalies were found in 50% of cases. Ear anomalies were found in 20% of cases. Genital anomalies were found in 10% of cases. On the other hand, in patients of group 2, consanguinity was positive in 80% of cases. Family history was positive in 20% of cases. Male : female ratio was 1.5 : 1. Short stature was found in 40% of cases, while microcephaly was found in 60% of cases. Conclusion: Some cases of Fanconi anemia are not associated with congenital anomalies. By increasing the dose of radiation for induction of breakage, it was found that the mean break/cell was increased. Therefore, radiation may be used to diagnose cases of FA whose cells are not responding to DEB or MMC. There were no significant correlations between the mean of chromosomal breakage and either of the height, the head circumference, the age of onset of hematological disorders, the severity index of hematological disorders or the number of congenital anomalies.