They [do more than] Interrupt Us from Sadness: Exploring the impact of participatory music making on social determinants of health and wellbeing for refugees in Australia

This paper reports on the outcomes of an exploratory narrative study on the impact of participatory music making on social determinants of health (SDOH) and wellbeing for refugees in Brisbane, Australia. A key component of this exploratory research was to map health and wellbeing outcomes of music participation using an existing SDOH framework developed by researchers in the field of health promotion (Schulz & Northridge, 2004). This paper maps reported health and wellbeing outcomes for five refugee and asylum seeker members of a participatory Brisbane-based music initiative, the Scattered People, along an SDOH continuum ranging from individual level through to macro level fundamental determinants of health.While most themes emerging from this study corresponded to distinct categories in the Schulz and Northridge SDOH framework, three key aspects, which were critical to the achievement of wellbeing for participants, did not fit any of the pre-defined categories. These were: cultural expression, music making, and consolidation of personal and social identity. The importance of those themes to participants suggests that music and wellbeing studies involving culturally diverse groups and from a SDOH perspective may need to consider broader, more relevant concepts. The paper provides recommendations for future interdisciplinary research in this field.

Yield of comparative genomic hybridization microarray in pediatric neurology practice

OBJECTIVE: The present study investigated the diagnostic yield of array comparative genomic hybridization (aCGH) in a large cohort of children with diverse neurologic disorders as seen in child neurology practice to test whether pathogenic copy number variants (CNVs) were more likely to be detected in specific neurologic phenotypes. METHODS: A retrospective cross-sectional analysis was performed on 555 children in whom a genetic etiology was suspected and who underwent whole-genome aCGH testing between 2006 and 2012. Neurologic phenotyping was performed using hospital medical records. An assessment of pathogenicity was made for each CNV, based on recent developments in the literature. RESULTS: Forty-seven patients were found to carry a pathogenic CNV, giving an overall diagnostic yield of 8.59%. Certain phenotypes predicted for the presence of a pathogenic CNV, including developmental delay (odds ratio [OR] 3.69 [1.30–10.51]), cortical visual impairment (OR 2.73 [1.18–6.28]), dysmorphism (OR 2.75 [1.38–5.50]), and microcephaly (OR 2.16 [1.01–4.61]). The combination of developmental delay/intellectual disability with dysmorphism and abnormal head circumference was also predictive for a pathogenic CNV (OR 2.86 [1.02–8.00]). For every additional clinical feature, there was an increased likelihood of detecting a pathogenic CNV (OR 1.18 [1.01–1.38]). CONCLUSIONS: the use of aCGH led to a pathogenic finding in 8.59% of patients. The results support the use of aCGH as a first tier investigation in children with diverse neurologic disorders, although whole-genome sequencing may replace aCGH as the detection method in the future. In particular, the yield was increased in children with developmental delay, dysmorphism, cortical visual impairment, and microcephaly

NEXMIF encephalopathy: an X-linked disorder with male and female phenotypic patterns

Purpose: Pathogenic variants in the X-linked gene NEXMIF (previously KIAA2022) are associated with intellectual disability (ID), autism spectrum disorder, and epilepsy. We aimed to delineate the female and male phenotypic spectrum of NEXMIF encephalopathy. / Methods: Through an international collaboration, we analyzed the phenotypes and genotypes of 87 patients with NEXMIF encephalopathy. / Results: Sixty-three females and 24 males (46 new patients) with NEXMIF encephalopathy were studied, with 30 novel variants. Phenotypic features included developmental delay/ID in 86/87 (99%), seizures in 71/86 (83%) and multiple comorbidities. Generalized seizures predominated including myoclonic seizures and absence seizures (both 46/70, 66%), absence with eyelid myoclonia (17/70, 24%), and atonic seizures (30/70, 43%). Males had more severe developmental impairment; females had epilepsy more frequently, and varied from unaffected to severely affected. All NEXMIF pathogenic variants led to a premature stop codon or were deleterious structural variants. Most arose de novo, although X-linked segregation occurred for both sexes. Somatic mosaicism occurred in two males and a family with suspected parental mosaicism. / Conclusion: NEXMIF encephalopathy is an X-linked, generalized developmental and epileptic encephalopathy characterized by myoclonic–atonic epilepsy overlapping with eyelid myoclonia with absence. Some patients have developmental encephalopathy without epilepsy. Males have more severe developmental impairment. NEXMIF encephalopathy arises due to loss-of-function variants

Autoantibodies to neuronal antigens in children with new-onset seizures classified according to the revised ILAE organization of seizures and epilepsies.

PURPOSE: Potentially pathogenic autoantibodies are found increasingly in adults with seizure disorders, including focal seizures and those of unknown cause. In this study, we investigated a cohort of children with new-onset seizures to see whether there were autoantibodies and the relationship to any specific seizure or epilepsy type. METHODS: We prospectively recruited 114 children (2 months to 16 years) with new-onset seizures presenting between September 2009 and November 2011, as well as 65 controls. Patients were clinically assessed and classified according to the new International League Against Epilepsy (ILAE) organization of seizures and epilepsies classification system. Sera were tested for autoantibodies to a range of antigens, blind to the clinical and classification details. KEY FINDINGS: Eleven (9.7%) of 114 patients were positive for one or more autoantibodies compared to 3 of 65 controls (4.6%, p = ns). Patients had antibodies to the voltage-gated potassium channel (VGKC) complex (n = 4), contactin-associated protein-like 2 (CASPR2) (n = 3), N-methyl-d-aspartate receptors (NMDARs) (n = 2), or VGKC-complex and NMDAR (n = 2). None had antibodies to glutamic acid decarboxylase, contactin-2, or to glycine, 2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl) propionic acid (AMPA), or γ-aminobutyric acid B receptors. Ten of these 11 patients were classified as having epilepsy according to the new ILAE organization of seizures and epilepsy. Although, there were no significant differences in the demographic and clinical features between antibody-positive and antibody-negative patients, the classification of "unknown cause" was higher in the antibody positive (7/10; 70%) compared with the antibody negative subjects (23/86; 26.7%; p = 0.0095, Fisher's exact test). Furthermore, four of these seven patients with epilepsy (57.1%) were classified as having predominantly focal seizures compared with 12 of the 86 antibody-negative patients (13.9%; p = 0.015). SIGNIFICANCE: Because autoantibodies were more frequent in pediatric patients with new-onset epilepsy of "unknown cause," often with focal epilepsy features, this group of children may benefit most from autoantibody screening and consideration of immune therapy