Aim: Early onset of psychopathology is often an index of a more severe clinical course and worse prognosis. This review examined the course of bipolar disorder (BD) with onset in childhood and adolescence, with a focus on persistence of symptoms, severity of illness, comorbidity, and functional impairment. Methods: The databases of PubMed, Embase, and PsycInfo were systematically searched for publications since 1990 reporting on long-term (12 months or longer) assessments of patients with early onset BD. Results: Forty-two relevant publications were identified, which reported on data derived from 15 different patient cohorts, including 7 prospective research psychopathology studies, 4 medical record reviews, 2 follow-ups of clinical trial samples, 1 managed care database, and 1 nationwide registry, for a total of 10,187 patients. The length of follow-ups ranged from 1.0 to 15 years. Diagnostic stability of BD ranged from 73% to 100% over ten years. Recovery rate from an index episode was 81.5–100% and recurrence rate was 35–67%. Suicide attempt cumulative prevalence in five years was 18–20%. Earlier age at the first episode predicted a more severe clinical course. Conclusions: Early onset BD persists over time through adolescence, with homotypic diagnostic continuity over the years, but heterogeneity in the severity of the clinical course. Whether early identification and treatment improves distal prognosis remains to be further investigated.

Aicardi-Goutières syndrome (AGS) is a genetically determined early onset encephalopathy characterized by cerebral calcification, leukodystrophy, and increased expression of interferon-stimulated genes (ISGs). Up to now, seven genes (TREX1, RNASEH2B, RNASEH2C, RNASEH2A, ADAR1, SAMHD1, IFIH1) have been associated with an AGS phenotype. Next Generation Sequencing (NGS) analysis was performed on 51 AGS patients and interferon signature (IS) was investigated in 18 AGS patients and 31 healthy controls. NGS identified mutations in 48 of 51 subjects, with three patients demonstrating a typical AGS phenotype but not carrying mutations in known AGS-related genes. Five mutations, in RNASEH2B, SAMHD1 and IFIH1 gene, were not previously reported. Eleven patients were positive and seven negatives for the upregulation of interferon signaling (IS > 2.216). This work presents, for the first time, the genetic data of an Italian cohort of AGS patients, with a higher percentage of mutations in RNASEH2B and a lower frequency of mutations in TREX1 than those seen in international series. RNASEH2B mutated patients showed a prevalence of negative IS consistent with data reported in the literature. We also identified five novel pathogenic mutations that warrant further functional investigation. Exome/genome sequencing will be performed in future studies in patients without a mutation in AGS-related genes.

Becker muscular dystrophy (BMD) is an X-linked neuromuscular disease attributable to mutations in DMD, leading to a deficient and less functional dystrophin, mainly in skeletal and cardiac muscle. Understanding the natural history of BMD is crucial for optimizing patient care and developing targeted treatments. Retrospective data were collected from 943 patients diagnosed with BMD based on a combination of clinical, biochemical and genetic criteria followed by 17 Italian neuromuscular centres. Patients’ demographics, main signs and symptoms at BMD onset, neuropsychiatric comorbidities, age at loss of ambulation, cardiac left ventricular ejection fraction, pulmonary forced vital capacity and DMD mutations were collected. Disease milestones were analysed in specific DMD mutational groups. The median age at the last assessment was 26.0 (16.6–41.9) years, with a median age at diagnosis of 7.5 (4.0–14.0) years. In 55% of patients, the diagnosis was prompted by the incidental finding of hyperCKaemia. At the last assessment, 13.5% of patients had lost the ability to walk at a median age estimated by Kaplan–Meier analysis of 69 years. Thirty per cent of patients exhibited left ventricular impairment and 2.7% respiratory involvement. Ten per cent of patients carried out-of-frame mutations, 4% nonsense mutations and 86% in-frame deletions/duplications. The subset of in-frame deletions was classified further based on the specific mutations. Patients carrying del45–49 compared with del45–47 were associated with an earlier loss of ambulation (P = 1 × 10−4), whereas patients with del45–55 (P = 0.005), del48 (P = 0.02) and del48–49 (P = 0.02) were correlated with a later loss of ambulation compared with del45–47. Both del45–55 (P = 0.002) and del48 (P = 0.003) were significantly associated with decreased odds of developing a pathological left ventricular ejection fraction compared with del45–47. Our results contribute to a better understanding of the natural history of BMD and capture precious data in the era of emerging therapies. The knowledge of the specific DMD mutation might help to define a prognosis in a subset of BMD patients and will serve as a model for the design of future therapies.

Central nervous system (CNS) involvement has been variously studied in pediatric neuromuscular disorders (NMDs). The primary goal of this study was to assess cognitive functioning in NMDs, and secondary aims were to investigate possible associations of cognitive impairment with motor impairment, neurodevelopmental delay, and genotype. This was a cross-sectional study of 43 pediatric patients, affected by six NMDs. Myotonic dystrophy type 1 (DM1) and glycogen storage disease type 2 (GSD2) patients had a delay on the Bayley-III scales. On Wechsler scales, DMD and DM1 patients showed lower FSIQ scores, with an intellectual disability (ID) in 27% and 50%, respectively. FSIQ was normal in Becker muscular dystrophy (BMD), GSD2, and hereditary motor sensory neuropathy (HMSN) patients, while higher individual scores were found in the spinal muscular atrophy (SMA) group. In the DM1 cohort, lower FSIQ correlated with worse motor performance (ρ = 0.84, p < 0.05), and delayed speech acquisition was associated with ID (p = 0.048), with worse cognitive impairment in the congenital than in the infantile form (p = 0.04). This study provides further evidence of CNS in some NMDs and reinforces the need to include cognitive assessment in protocols of care of selected pediatric NMDs.

Background: Hospitals can be especially stressful for children with autism spectrum disorder (ASD) due to the communication and social skills deficits, lower capacity to adapt to disruption, and sensory hypersensitivity that are typical of these patients. Purpose: This study investigated how health-care professionals (HPs) experienced the clinical care and management of children with ASD undergoing medical testing in a day hospital setting, and assessed the rate of successful completion of laboratory tests and instrumental examinations. Methods: A cross-sectional questionnaire was administered to 45 HPs, inquiring about their experience in obtaining blood and urine tests, ECG, audiometry, and EEG from children with ASD. The clinical sample included 153 consecutively referred children with ASD (74.5% males, mean age 5.6 years) undergoing a medical diagnostic work-up as part of their diagnostic evaluation. The success rate of completing the various assessments was examined. Results: HPs identified aggressive behavior and communication deficits as the major challenges when providing care to children with ASD. The parents were seen as an important resource for managing the children. The completion rate of the laboratory tests and instrumental examinations was high (between 88.5% and 98.4% according to the specific type of examination). The lowest non-completion rate was found for the EEG (12.5%). Conclusions: Despite considerable challenges being reported by HPs in managing children with ASD, the scheduled assessments could be completed in the large majority of cases. Targeted approaches to preventing aggressive behaviors and obviating the communication barriers in children with ASD undergoing hospital exams are warranted.

Suicide is a leading cause of death all over the world. Suicide prevention is possible and should be pursued through a variety of strategies. The importance of the arts for positive health outcomes has been increasingly evidenced. This scoping review aimed to identify the possible role of the performing arts—defined as a type of art performed through actions such as music, dance, or drama executed alive by an artist or other participant in the presence of an audience,—in suicide prevention programs. PubMed, Embase, PsycINFO, CINAHL, ProQuest Psychology Database, Scopus, and Web of Science were searched using terms in English for publications of original studies that included performing arts in suicide prevention programs. Thirty-five studies conducted between 1981 and 2021 were identified, of which only five were randomized clinical trials and four quasi-randomized studies. Interventions used different performing arts to improve awareness, self-efficacy, and soft skills relevant to suicide prevention. Studies were addressed mainly to gatekeepers but also directly to at-risk populations. While the study designs do not allow inferences to be drawn about the effectiveness of performing arts in preventing suicide, the review found that performing arts have been successfully implemented in suicide prevention programs. Research to evaluate the possible therapeutic benefit is warranted.