Background: 22q11.2 deletion syndrome (22q) is a chromosome disorder, where a segment of chromosome 22, located at 811.2, is missing. This study aims to investigate the relationship between a number of parent-reported comorbid conditions including gastrointestinal symptoms, sleep problems, autism spectrum disorder (ASD) symptoms and behavior problems in children and adolescents with 22q deletion syndrome.Method: The Gastrointestinal Symptom Inventory, Children's Sleep Habits Questionnaire, Behavior Problem Inventory-Short Form and the Social Communication Questionnaire were completed by parents of 149 children and adolescents aged 3-18 years with a diagnosis of 22q.Results: A series of correlations and hierarchical multiple regressions were conducted to examine the relationships between GI symptoms, sleep problems and behavior problems in children and adolescents with 22q deletion syndrome. A significant moderate relationship was found between GI symptoms and sleep problems. Gender and ASD symptoms predicted GI symptoms. Significant small relationships were found between GI symptoms and self-injurious behavior. Significant small to moderate relationships were found between sleep problems and self-injurious behavior, aggressive/destructive behavior, and sterotyped behavior. Sleep problems predicted challenging behavior.Conclusions: This research demonstrated the importance of studying the relationship between comorbidities, including gastrointestinal symptoms, sleep problems, and behavior problems and how they shape the phenotype of 22q deletion syndrome.