Moreover, while digestive problems associated with gastroesophageal reflux or abnormal intestinal motility may be managed by parents or caregivers, signs and symptoms of liver disease often go unnoticed unless tests are performed, even though at least two major candidate genes for liver disease have been identified in the 22q13 region (patatin-like phospholipase domain containing 3, PNPLA3, and cytochrome P450 2D6, CYP2D6) and liver dysfunction might exert secondary effects on other PMS phenotypes [5,6,8,11]. Here, PNPLA3 is linked to gastroesophageal reflux disease.