A genetic disorder caused by the microdeletion of the long arm of 22th chromosome is the most common microdeletion syndrome in humans. It is estimated that 22q11.2 deletion affects one in every 1,000 foetales and one in 4,000 live births. During the neonatal period, the 22q11.2 deletion syndrome manifests itself in children in the form of dysmorphic facial features, and the results of ultrasound imaging tests reveal thymus hypoplasia, urinary tract disorders or brain impairments. The picture is completed by congenital heart diseases which indicate a high probability of the syndrome. This report describes four cases of newborns with 22q11.2 syndrome, presenting with a variety of clinical findings typical for this genetic disorder. The patients present symptoms ranging from mild to life-threatening conditions. The severity of the congenital heart defect determines the survival rate in infancy. Each needs of each patient must be tailored to his or her specific medical problems. A holistic approach, addressing medical and behavioural needs, can be very helpful.