Case Series: ADHD Phenotype in a Family with NPY Gene Microduplication

Background: Neuropeptide Y is a highly conserved neuropeptide involved in several physiological processes, including stress regulation, appetite control, and cognitive functioning. Emerging evidence suggests that alterations in neuropeptide Y signaling may contribute to neurodevelopmental and behavioural phenotypes. This study describes a family carrying a microduplication involving the neuropeptide Y gene on chromosome 7p15.3, with the aim of exploring its potential association with attention deficit/hyperactivity disorder and specific cognitive vulnerabilities, particularly in the memory domain. Methods: Five individuals across three generations of one family carrying the duplication underwent comprehensive clinical and neuropsychological assessment, including standardized measures of intellectual functioning, attention, memory, adaptive skills, and psychopathology. Results: A consistent pattern of attentional difficulties was observed across affected individuals, accompanied by internalizing features such as anxiety. Cognitive evaluation revealed selective vulnerabilities in memory domains, involving both verbal and spatial components, across short- and long-term processes. Intellectual functioning ranged from borderline to average levels. In addition, increased body weight and hormonal imbalances were recurrently observed, indicating a possible contribution of neuropeptide Y dysregulation to metabolic phenotype in association with behavioural features. Conclusions: These findings support the hypothesis that duplication of the neuropeptide Y gene may be associated with a distinct neurobehavioural profile characterized by attentional difficulties, internalizing symptoms, and selective memory vulnerabilities. The co-occurrence of obesity further highlights the potential role of neuropeptide Y in linking metabolic and neurodevelopmental processes. Although based on a small familial sample, this study contributes to the characterization of genotype-phenotype correlations involving neuropeptide Y and underscores the need for further investigation in larger cohorts.