Summary: Down syndrome (trisomy 21) is the most common aneuploidy found in nature. It is a set of abnormalities in the structure and functioning of the body caused by the presence of an additional whole or fragment of chromosome 21. It occurs in 1 : 800–1000 live births. The risk of having an affected child increases with the age of the mother. It is associated with characteristic physical features. Most children with Down syndrome are born at their planned labor date, eutrophic, i.e. with appropriate body weight and length. There is an increased risk of congenital malformations, including heart defects. In the article, we describe the case of a newborn with trisomy 21 born in the Neonatology Department of the Medical University of Gdańsk. We discuss specific clinical symptoms in newborns with Down syndrome, present difficulties with adaptation to extrauterine life and other health problems that may occur in the neonatal and infant periods. In presented neonate, trisomy 21 was diagnosed prenatally. After delivery, adaptation disorders, persistent pulmonary hypertension of the newborn, pathological neonatal jaundice and cholestasis were observed. A congenital heart defect was diagnosed: ventricular septal defect. In infancy, hypothyroidism was diagnosed. We present the differential diagnosis of these problems. Caring for a child with Down syndrome requires enormous commitment from parents and healthcare professionals. Early detection of life-threatening defects is important in neonatal period. For this reason, echocardiographic and cardiological evaluation is recommended. Regardless of type of congenital defects identified, children with Down syndrome should be provided with the same care and treatment as healthy newborns. Children should remain under multidisciplinary care. Family should receive psychological and social support.