Background: Sex chromosome aneuploidies (SCAs) are a group of disorders characterised by an abnormal number of sex chromosomes. Collective prevalence rate of SCAs is estimated to be around 1 in 400–500 live births; sex chromosome trisomies (e.g., XXX, XXY, XYY) are most frequent, while tetra- and pentasomies (e.g., XXXX, XXXXX, XXXY, XXXXY) are rarer, and the most common is 48, XXYY syndrome. The presence of additional X and/or Y chromosomes is believed to cause neurodevelopmental differences, with increased risk for developmental delays, language-based learning disabilities, cognitive impairments, executive dysfunction, and behavioural and psychological disorders. Aim of the Study: Our review has the purpose of analysing the neurocognitive, linguistical and behavioural profile of patients affected by sex chromosomes supernumerary aneuploidies (tetrasomy and pentasomy) to better understand the specific areas of weakness, in order to provide specific rehabilitation therapy. Methods: The literature search was performed by two authors independently. We used MEDLINE, PubMed, and PsycINFO search engines to identify sources of interest, without year or language restrictions. At the end of an accurate selection, 16 articles fulfilled the inclusion and exclusion criteria. Results and Conclusions: International literature has described single aspects of the neuropsychological profile of 48, XXYY and 49, XXXXY patients. In 48, XXYY patients, various degrees of psychosocial/executive functioning issues have been reported and there is an increased frequency of behavioural problems in childhood. Developmental delay and behavioural problems are the most common presenting problems, even if anxiety, depression and oppositional defiant disorder are also reported. They also show generalized difficulties with socialization and communication. Cognitive abilities are lower in measures of verbal IQ than in measures of performance IQ. Visuospatial skills are a relative strength compared to verbal skills. In patients with 49, XXXXY, both intellectual and adaptive functioning skills fall into the disability range, with better non-verbal cognitive performance. Speech and language testing reveals more deficits in expressive language than receptive language and comprehension. Anxiety, thought problems, internalizing and externalizing problems, and deficits in social cognition and communication are reported. Behavioural symptoms lessen from school age to adolescence, with the exception of thought problems and anxiety. Individuals affected by sex chromosome aneuploidies show testosterone deficiency, microorchidism, lack of pubertal progression and infertility. Hormone replacement therapy (HRT) is usually recommended for these patients: different studies have found that testosterone-based HRT benefit a wide range of areas initiated in these disorders, affecting not only neuromotor, cognitive and behavioural profile but also structural anomalies of the brain (i.e., increase of volume of grey temporal lobe matter). In conclusion, further studies are needed to better understand the neuropsychological profile with a complete evaluation, including neurocognitive and psychosocial aspects and to establish the real impact of HRT on improving the cognitive and behavioural profile of these patients.

Background: Emotional dysregulation (ED) is a transdiagnostic feature of multiple adolescent psychiatric disorders and a predictor of functional impairment and self-harming behaviors. Despite its clinical relevance, pharmacological treatments targeting ED in youth remain underexplored. This retrospective study investigated the clinical effectiveness and tolerability of adjunctive lithium therapy in adolescents with severe ED, independent of specific diagnostic categories. Methods: A total of 35 inpatients (13–17 years) with significant ED were divided into two groups based on pharmacological treatment: lithium add-on therapy (Li group, n = 17) and standard therapy without lithium (Control group, n = 18). Clinical severity (CGI-S) and global functioning (C-GAS) were assessed at baseline (T0), 6 months (T1), and 12 months (T2). A mixed-design ANOVA was performed to assess group × time interactions. Adverse events and treatment adherence were also examined. Results: At T1, the Li group showed a significantly greater reduction in symptom severity (CGI-S) compared to the Control group (p = 0.029). Global functioning (C-GAS) improved over time in both groups (p < 0.001), with no significant interaction effects. Adverse effects, primarily metabolic and endocrine, were more frequent in the Li group but did not reduce adherence. Conclusions: Adjunctive lithium therapy may reduce symptom severity in adolescents with severe ED without negatively affecting treatment tolerability or adherence. These findings support the potential utility of lithium in complex adolescent cases and warrant further prospective research.