Children with Down syndrome are often identified at birth as a result of the physical characteristics associated with the syndrome. Some children exhibit only a few characteristics; others exhibit many. Because some of these features are also seen in people without Down syndrome, genetic testing must be done to confirm diagnosis. The most common features associated with Down syndrome include:

• Low muscle tone (babies appear "floppy")
• Flat facial features, with a small nose
• Upward slant to the eyes
• Small skin folds on the inner corner of the eyes
• Small, abnormally shaped ears
• Single deep crease across the centre of the palm
• Hyperflexibility (excessive ability to flex joints)
• Fifth finger has only one flexion furrow instead of two
• Extra space between the big toe and the second toe
• Enlarged tongue that tends to stick out