Trisomy 18 is a devastating genetic disorder that can be characterized by multiple congenital anomalies. Some of these anomalies have no medical significance, but merely provide clues to suggest the diagnosis. The most common form of trisomy 18 is the nondisjunction type, which affects every cell of the body with an extra chromosome 18. Affected infants are typically born with a prominent occiput, short eye fissures with droopy eyelids, micrognathia, external ear variations, clenched fist with index finger overlapping the third finger and fifth finger overlapping the fourth, small fingernails and toenails, underdeveloped or altered thumbs, “rocker-bottom” feet, and redundant skin at the back of the neck. Congenital heart defects are common. The mortality rate among infants with trisomy 18 is high as a result of cardiac and renal malformations, feeding difficulties, sepsis, and central apnea caused by central nervous system defects. A case study is provided.