Previous research supports application of the Double ABCX model of family adaptation of parents of children with autism spectrum disorder and other pervasive developmental disorders. This is the first study to consider processes of adaptation among parents of children with agenesis of the corpus callosum (ACC). Using a quantitative cross-sectional design, an international sample of 266 mothers of children, aged 12 or under, with ACC completed an online survey. Parental reports of stress, resources, coping, and sense of coherence were evaluated as predictors of four subdimensions of parental quality of life for 178 mothers. In general, findings support the Double ABCX model as a viable approach to understanding processes that are related to quality of life among this group of mothers.