The methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) method enables precise diagnosis of congenital syndromes caused by genomic imprinting, including Prader-Willi syndrome (PWS), Angelman syndrome (AS), Beckwith-Wiedemann syndrome (BWS) and Russell-Silver syndrome (RSS). The molecular etiology and clinical presentation of these syndromes varies significantly with phenotypic differences arising from distinct genetic mechanisms. The aim of this study was to analyze the copy number and methylation status of imprinted genes located in the PWS/AS region (15q11-q13) and the BWS/RSS region (11p15.5, 7q32, 7p12, and 14q32) and to compare the phenotypes of each patient based on the molecular mechanism of the disease and confirmation of the initial diagnosis. The study included 104 unrelated patients referred for diagnostics to the Department of Pediatrics at UHC Zagreb. The genetic cause for PWS was identified in 37% of patients, for AS in 44% and for BWS in 52% of patients. The lowest confirmation rate (17%) was in the group of patients with a clinical presentation indicative of RSS. No statistically significant difference in phenotypes was found based on the molecular cause of the disease for PWS and RSS. Additionally, there was no statistically significant difference between the phenotypes of patients confirmed and not confirmed by the MS-MLPA method. This study supports the hypothesis that an early identification of the genetic etiology of syndromes caused by the genomic imprinting disorders using molecular cytogenetic techniques allows for better prediction of patient phenotypes, enabling thus a more effective individualized therapy.