DIAGNOSIS OF MICRODELETION SYNDROMES - HIGH-RESOLUTION CHROMOSOME ANALYSIS VERSUS FLUORESCENCE IN-SITU HYBRIDIZATION

Contiguous gene syndromes are characterized by deletions or duplicatio ns of specific chromosomal segments involving clusters of single genes . Although these syndromes are associated with distinct clinical pheno types, these features are difficult to distinguish in the newborn and early childhood periods. In such cases, demonstration of chromosomal i nvolvement through cytogenetic studies is of vital importance in arriv ing at an accurate diagnosis. In this article results of microdeletion analysis of 31 cases comprising 16 cases of Prader-Willi syndrome, 3 of Angelman syndrome, 7 of Miller-Dieker syndrome, and 5 of DiGeorge s yndrome are reported. All patients were studied with both high-resolut ion chromosome analysis and fluorescence in situ hybridization. In the majority of cases there is 100% concordance between the two technique s. However, in one patient suspected of having DiGeorge syndrome with a normal karyotype at the 750 band level, fluorescence in situ hybridi zation identified a deletion within the critical region. Without fluor escence in situ hybridization studies on this patient, it would not ha ve been possible to confirm the diagnosis of DiGeorge syndrome cytogen etically. Based on these results and other studies reported in the lit erature, it is recommended that all suspected cases of microdeletion s yndromes should be studied using fluorescence in situ hybridization, i rrespective of high-resolution chromosome results. However, because of the difficulties associated with clinical diagnosis of these syndrome s, fluorescence in situ hybridization should not replace standard chro mosome analysis.