Background: 47,XYY syndrome is a relatively common sex chromosome aneuploidy that remains largely underdiagnosed. While its somatic phenotype is often mild, growing evidence indicates a substantial burden of neurodevelopmental and psychiatric morbidity. However, the characterization of the neuropsychiatric phenotype across development, particularly during adolescence, and the associated treatment challenges remain incomplete. Objectives: To provide a comprehensive narrative review of the neuropsychiatric phenotype of 47,XYY syndrome and to illustrate clinical complexity and treatment response through a case series of adolescents. Methods: A narrative review of the literature was conducted focusing on genetics, neurodevelopmental and psychiatric features, neuroimaging and neurophysiology findings, clinical course, and management strategies in 47,XYY syndrome. This review is complemented by a case series of adolescents with confirmed 47,XYY karyotype, evaluated for developmental history, psychiatric comorbidity and response to pharmacological and non-pharmacological interventions. Results: The literature consistently describes increased risks of language impairment, executive dysfunction, ADHD, autism spectrum traits, and emotional and behavioral dysregulation in males with 47,XYY syndrome. Psychiatric vulnerability appears to increase during adolescence and adulthood, with elevated rates of mood, psychotic, and substance use disorders. The presented cases illustrate a convergent clinical trajectory marked by early developmental delays, progressive behavioral dysregulation in adolescence and limited or inconsistent response to multiple classes of psychotropic medications, suggesting a pattern of pharmacoresistance in a subset of patients. Conclusions: 47,XYY syndrome is associated with a distinct and heterogeneous neuropsychiatric phenotype that extends beyond early neurodevelopmental disorders. Early diagnosis alone may be insufficient to prevent severe psychiatric outcomes, highlighting the need for long-term monitoring and integrated, multidisciplinary management. Further research is required to identify early predictors of high-risk trajectories and to optimize treatment strategies for this population.

Background: Adolescents with neurodevelopmental disorders (NDDs), particularly autism spectrum disorder (ASD) and borderline intellectual functioning/intellectual disability (BIF/ID), represent a clinically complex population in psychiatric emergency settings, with unclear contributions to acute psychopathology and suicide risk. Aims: This study examined whether ASD and BIF/ID differentially influence clinical severity, psychopathological profiles, and suicidality in adolescents admitted for psychiatric emergencies, comparing high-functioning ASD, ASD with cognitive impairment, and adolescents without NDDs. Methods: We conducted a retrospective, single-center cohort study including 206 consecutive patients aged 11–17 years admitted to a psychiatric emergency unit between January 2022 and December 2023. Patients were stratified into four groups: ASD (ASD-HF; ASD-BIF/ID), BIF/ID and N-ASD/N-BIF/IDClinical severity, global functioning, psychiatric diagnoses, adverse childhood experiences, emotional dysregulation, and suicidality were assessed using standardized diagnostic and behavioral measures. Group comparisons were performed to identify predictors of suicidality. Results: ASD-BIF/ID patients exhibited the lowest global functioning, whereas ASD-HF adolescents showed functioning comparable to controls. Suicidal ideation and behaviors were significantly more frequent in ASD-HF. BIF/ID was associated with greater behavioral impairment and lower suicidality. Conclusions: ASD and BIF/ID may differentially shape psychiatric emergency presentations. Adolescents with high-functioning ASD showed a higher prevalence of suicidality in this specific clinical context. Limits: This study is limited by its cross-sectional, single-center, and retrospective design, small and uneven subgroup sizes, and assessment tools not specifically validated for autistic or intellectually disabled populations. The high prevalence of bipolar spectrum disorders may reflect referral bias. Despite these limitations, adolescents with high-functioning ASD exhibited elevated suicidality, underscoring the importance of risk assessment adapted to cognitive and diagnostic profiles.