Chromosomal abnormalities are now considered a common cause of intellectual disability. With increased genetic testing, phenotyping and technological advancements, many new syndromes have been identified. This review sought to explore parental stress and adjustment in the context of rare genetic syndromes to evaluate their clinical impact. A systematic review of English peer-reviewed literature across three databases (PsycINFO, Medline, CINAHL) was completed and 69 articles were included. Parents of children with rare genetic syndromes experienced greater distress relative to other disabilities. Differences in parental wellbeing were syndrome-specific relative to ASD thus demonstrating the need to consider the contribution of syndrome-specific phenotypes. Child emotional and behavioural difficulties were the most consistent predictor of parental distress. Research reflecting other factors such as physical health, syndrome-specific behaviours, benefit finding and, parental appraisal in the context of a rare genetic aetiology is required in order to support parental adjustment in these conditions.