Current research in schizophrenia suggests that negative symptoms cannot be considered a unitary construct and should be divided in two dimensions: lack of motivation and impoverishment of expression. In addition, negative symptoms are particularly related to decreased daily-life functioning. In the present study, we aimed to replicate these results in a sample of participants with 22q11.2 deletion syndrome (22q11DS), a neurogenetic condition associated with high risk of developing schizophrenia. We also expected to observe an association between the COMT Val/Met polymorphism and negative symptoms. We examined the factorial structure of negative symptoms in a sample of 47 individuals with 22q11DS using the Structured Interview for Prodromal Symptoms (SIPS) and the Positive and Negative Syndrome Scale (PANSS). We also performed stepwise regression analyses to investigate the associations between negative symptoms, adaptive skills and the COMT Val/Met polymorphism. Negative symptoms were explained by a two-factor solution, namely the "amotivation and social withdrawal" and the "emotional withdrawal and expression" dimensions. The motivational dimension was significantly associated with daily-life functioning. Met carriers were rated as experiencing significantly more symptoms of amotivation. The results are interpreted in the light of existing cognitive models in the field of motivation and schizophrenia.