Objective: DiGeorge Syndrome (DGS), caused by a submicroscopic deletion in chromosome 22 (22q11.2), is the most common microdeletion syndrome in humans with an incidence of 1/400 live births. The condition is inherited in an autosomal dominant manner, though almost 90 % is due to a de novo mutation. Its phenotype ranges from mild to severe and it comprises congenital heart disease, palatal abnormalities, characteristic facial features, immune deficiency, developmental delay, parathyroid hypoplasia and renal, ocular, and skeletal malformations. Methods: We illustrate the presentation modalities of DGS in different ages through 4 clinical cases, patients that presented in the Pediatric Neurology Department in the last 10 years. Two patients had classical phenotypes and the others had global developmental delay and dysmorphic features; their diagnosis was confirmed after screening with arrayCGH. Results: Patient 1, a 4 year old boy with characteristic facial features, severe hipogammaglobulinemia and an interrupted Aortic arch. Patient 2, a 5 year old boy with characteristic DGS facial features, palatoschisis, hypotonia and global developmental delay. Both patients were diagnosed in the first month of life. Both phenotypes, highly suggestive since birth of classical DGS were confirmed through FISH (microdeletion of 22q11.2 and TBX1 gene). Patient 3, male, aged 14 has dysmorphic features, language and cognitive delay and anxiety disorder. Patient 4, female, aged 16, has pronounced facial dysmorphism both typical for DGS and unspecific features and severe developmental delay. They presented intellectual delay of unknown causes, both showing particular features, language delay and psychiatric disorders. An extended genetic screening with arrayCGH showed 22q11.21 deletions, demonstrating the broad phenotype of DGS. Conclusion: We emphasize the importance of genetic screening in cases of developmental delay which can lead to an early diagnosis and the formulation of an early intervention plan in order to prevent and limit the complications associated with DGS.