Spinal muscular atrophy (SMA) is an autosomal recessively inherited progressive neuromuscular disease caused in 95% of deletions in the SMN1 gene. SMA can also be suspected along with other clinical manifestations such as mental retardation, global developmental delay, epilepsy, autism, neurological syndromes and birth defects. We report 2 cases of 2 month and respectively 16 month boys born at term in a no- consanguineous families. Both children presented with severe hypotonia with lack of reflexes and dynamics, suggesting SMA and other clinical manifestations. The molecular–genetic examination of SMN1 gene through PCR-RFLP and qPCR methods showed deletions of exons 7 and 8 for one of them but not for the other patient. At the same time, considering other clinical manifestations associated with chromosomal genetic abnormalities, the constitutional karyotype with subsequent molecular karyotype investigation was indicated. Subsequent the result of the constitutional karyotype was normal (46 XY) for both. Molecular karyotype, trough Array-CGH method, identified the following unbalanced haploinsufficient genetic changes: a 1398 Kb microdeletion in the region of chromosome 5q13.2 (of which OMIM registered genes such as SMN1, NAIP, GTF2H2, SERF associated with SMA) and a microdeletion of 4832 Kb in the region of chromosome 10q11.22-q11.23 (of which 6 morbid genes, registered OMIM) for patient without SMA diagnosed and for patient of 2 mo, with SMA diagnosed, there have been identified unbalanced genomic abnormalities (461kb duplication on chr1q and 1.78Mb deletion on chr5q, among them are the SMN1 and SMN2 genes) and regions with LOH (3.6Mb region on chr1p and 4.8Mb region on chr14q including TMEM260 gene). In this cases, a detailed phenotypic and genotypic approach revealed that the diagnosis or suspection of SMA was mimicked by much more complex genomic abnormalities such as microdeletion and microduplication of chromosomal sectors that are too small to be detected by conventional cytogenetic methods. Molecular karyotype is extremely important in clinical utility for patients with such genomic changes, both in diagnosis and in long-term management and the determination of the risk of recurrence. Its scientific utility is also significant, with new microdeletion or microduplication syndromes being recognized and clinically delineated.