Abstract This chapter reviews background information about the incidence, risk factors, genetics, recurrence risk, and epidemiology of isolated and syndromic omphalocele. The distinct anatomy of omphalocele is contrasted with other types of abdominal wall defects such as umbilical hernia, gastroschisis, cloacal exstrophy, and limb-body wall complex. The discussion on the differential diagnosis of omphalocele summarizes its common causes, including environmental and teratogenic agents (ART, maternal diabetes, SSRI, valproic acid), chromosome anomalies (aneuploidy, tetrasomy 12p, UPD14), and single gene disorders that feature multiple congenital anomalies. The chapter gives recommendations for evaluation and management. A clinical case presentation features an infant with omphalocele and a narrow bell shaped thorax with “coat hanger” ribs caused by paternal uniparental disomy for chromosome 14.