Utilisation of exome sequencing for muscular disorders in Thai paediatric patients: diagnostic yield and mutational spectrum.

Muscular dystrophies and congenital myopathies are heterogeneous groups of inherited muscular disorders. An accurate diagnosis is challenging due to their complex clinical presentations and genetic heterogeneity. This study aimed to determine the utilisation of exome sequencing (ES) for Thai paediatric patients with muscular disorders. Of 176 paediatric patients suspected of genetic/inherited myopathies, 133 patients received a molecular diagnosis after performing conventional investigations, single gene testing, and gene panels. The remaining 43 patients from 42 families could be classified into three groups: Group 1, MLPA-negative Duchenne muscular dystrophy (DMD) with 9 patients (9/43; 21%), Group 2, other muscular dystrophies (MD) with 18 patients (18/43; 42%) and Group 3, congenital myopathies (CM) with 16 patients (16/43; 37%). All underwent exome sequencing which could identify pathogenic variants in 8/9 (89%), 14/18 (78%), and 8/16 (50%), for each Group, respectively. Overall, the diagnostic yield of ES was 70% (30/43) and 36 pathogenic/likely pathogenic variants in 14 genes were identified. 18 variants have never been previously reported. Molecular diagnoses provided by ES changed management in 22/30 (73%) of the patients. Our study demonstrates the clinical utility and implications of ES in inherited myopathies.

Neurological complications associated with influenza in hospitalized children.

BACKGROUND: Influenza is a known respiratory and potential neurotropic virus. This study aimed to determine the prevalence and outcomes of influenza-related neurological complications among hospitalized children. METHODS: All medical records of hospitalized children aged <18 years old diagnosed with influenza at a tertiary care hospital in Bangkok were retrospectively reviewed. Influenza infection was confirmed by rapid antigen or reverse transcription polymerase chain reaction tests. Neurological characteristics and clinical outcomes were analyzed using the Pediatric Cerebral Performance Category Scale. RESULTS: From 2013 to 2018, 397 hospitalized children with a median age of 3.7 years (interquartile range [IQR]: 1.6-6.9) were included. The prevalence of neurological complications, including seizure or acute encephalopathy, was 16.9% (95% confidence interval [CI]: 13.3-20.9). Influenza A and B were identified in 73.1% and 26.9% of the patients, respectively. Among 39 (58.2%) acute symptomatic seizure cases, 25 (37.3%) children had simple febrile seizures, 7 (10.4%) had repetitive seizures, and 7 (10.4%) had provoked seizures with pre-existing epilepsy. For 28 (41.8%) encephalopathy cases, the clinical courses were benign in 20 (29.9%) cases and severe in 8 (11.9%) cases. Ten (14.9%) children needed intensive care monitoring, and 62 (93.5%) fully recovered to their baselines at hospital discharge. Predisposing factors to the neurological complications included a history of febrile seizure (adjusted odds ratio [aOR]: 20.3; 95% CI: 6.6-63.0), pre-existing epilepsy (aOR: 3.6; 95% CI: 1.3-10.2), and a history of other neurological disorders (aOR: 3.5; 95% CI: 1.2-10.2). CONCLUSIONS: One fifth of hospitalized children with influenza had neurological complications with a favorable outcome. Children with pre-existing neurological conditions were at higher risk for developing neurological complications.

Effect of Mozart K.448 on interictal epileptiform discharges in children with epilepsy: A randomized controlled pilot study.

BACKGROUND: Epilepsy is a common pediatric neurologic disease in Thailand. However, the mainstay antiepileptic pharmacotherapies can induce severe side effects. While the benefit of playing Mozart K.448 music has been studied as an alternative, supplementary, nonpharmacologic treatment for epilepsy, the literature features limited few randomized controlled trial studies of children. OBJECTIVE: We aimed to study the effect of Mozart K.448 for two pianos on interictal epileptiform discharges (IEDs), quantitative electroencephalogram (qEEG), and heart rate variability (HRV) in patients with epilepsy. METHODS: We employed a single-blinded randomized trial design with a placebo control. The treatment group listened to the first 8 min of Mozart K.448 for two pianos during EEG recording. The control group underwent an EEG recording of the same duration in a quiet environment. Interictal epileptiform discharges were manually counted for 8 min before, during, and after the song was plated. Quantitative electroencephalogram and HRV were analyzed in each period. RESULT: A total of 32 patients aged 0-18 years were enrolled. There were 12 patients in the music group and 14 patients in the control group; 67% of the patients in the former exhibited significantly decreased IEDs while listening to the music compared with 42% of the patients in the quiet group (RR [Relative Risk Reduction]: 0.72, p-value: <0.001, 95% confidence interval [CI]: 0.69-0.74). During music exposure, qEEG demonstrated an increase in the delta/theta to alpha/beta ratio relative to that of controls (median in music: +3% and control: -6%, p-value: 0.520). Heart rate variability analyses showed a decrease in the ratio of low frequency to high frequency (LF/HF), which represents parasympathetic activity during music exposure (decrease of 34%, p-value: 0.382). CONCLUSION: The present study showed that Mozart K.448 reduced the number of IEDs in children with epilepsy and that Mozart K.448 could enhance parasympathetic activity. However, possibly because of the small study population, statistical significance was not reached. Our study revealed the considerable potential of music in the treatment of pediatric epilepsy.