The 22q11 deletion syndrome (22q11DS) is one of the most common genomic disorders in humans, affecting around 1:2,000 to 1: 4,000 people. 22q11DS affects multiple body systems and is associated with multiple physical problems. Given the high rate of physical morbidity associated with the 22q11DS, it was hypothesized that it would exert a high psychosocial impact on patients and their relatives. To investigate this, a systematic review of the literature and narrative synthesis was performed. Three major themes emerged. First, the complex and conflicting emotions experienced by family members resulting from the diagnosis. Second, the pervasive educational and health‐care challenges associated with the diagnosis and third that people affect by 22q11DS strived for individualism. The results of this review help to inform clinical management of families with 22q11DS.