Genetic Testing in Pediatric Epilepsy: Tools, Tips, and Navigating the Traps.

With the advent of high-throughput sequencing and computational methods, genetic testing has become an integral part of contemporary clinical practice, particularly in epilepsy. The toolbox for genetic testing has evolved from conventional chromosomal microarray and epilepsy gene panels to state-of-the-art sequencing techniques in the modern genomic era. Beyond its potential for therapeutic benefits through precision medicine, optimizing the choice of antiseizure medications, or exploring nonpharmacological therapeutic modalities, genetic testing carries substantial diagnostic, prognostic, and personal implications. Developmental and epileptic encephalopathies, the coexistence of neurodevelopmental comorbidities, early age of epilepsy onset, unexplained drug-refractory epilepsy, and positive family history have demonstrated the highest likelihood of yielding positive genetic test results. Given the diagnostic efficacy across different testing modalities, reducing costs of next-generation sequencing tests, and genetic diversity of epilepsies, exome sequencing or genome sequencing, where feasible and available, have been recommended as the first-tier test. Comprehensive clinical phenotyping at the outset, corroborative evidence from radiology and electrophysiology-based investigations, reverse phenotyping, and periodic reanalysis are some of the valuable strategies when faced with inconclusive test results. In this narrative review, the authors aim to simplify the approach to genetic testing in epilepsy by guiding on the selection of appropriate testing tools in the indicated clinical scenarios, addressing crucial aspects during pre- and post-test counseling sessions, adeptly navigating the traps posed by uncertain or negative genetic variants, and paving the way forward to the emerging testing modalities beyond DNA sequencing.

Child Neurology: Allgrove Syndrome: An Intriguing Etiology of Motor Neuron Disease in Children

Motor neuron diseases are a rare group of neurodegenerative disorders with considerable phenotypic heterogeneity and a multitude of etiologies in the pediatric population. In this study, we report 2 unrelated adolescents (a boy and a girl) who presented with 4-6 years of progressive difficulty in walking, thinning of limbs, and gradually progressive darkening of the skin. Examination revealed generalized hyperpigmentation of skin and features suggestive of motor neuron involvement such as tongue atrophy, wasting of distal extremities, and brisk deep tendon reflexes. On detailed exploration for systemic involvement, history of dysphagia, inability to produce tears, and Addisonian crises were evident. An etiologic diagnosis of Allgrove syndrome, which is characterized by a triad of achalasia, alacrimia, and adrenal insufficiency was considered. Next-generation sequencing revealed pathogenic variants in the AAAS gene, confirming the diagnosis. Steroid replacement therapy was initiated along with relevant multidisciplinary referrals. The disease stabilized in the boy and a significant improvement was noted in the girl. These cases highlight the value of non-neurologic cues in navigating the etiologic complexities of motor neuron diseases in children and adolescents. It is imperative for neurologists to develop awareness of the diverse neurologic manifestations associated with Allgrove syndrome because they are often the first to be approached. A multidisciplinary team of experts including neurologists, endocrinologists, gastroenterologists, ophthalmologists, and dermatologists is essential for planning comprehensive care for these patients.

Psychological and Behavioral Impact of Lockdown and Quarantine Measures for COVID-19 Pandemic on Children, Adolescents and Caregivers: A Systematic Review and Meta-Analysis.

BACKGROUND: During the current ongoing COVID-19 pandemic, psychological problems like anxiety, depression, irritability, mood swings, inattention and sleep disturbance are fairly common among quarantined children in several studies. A systematic review of these publications to provide an accurate burden of these psychiatric/behavioral problems is needed for planning mitigating measures by the health authorities. METHODS: Different electronic databases (MEDLINE, EMBASE, Web of Science, CENTRAL, medRxiv and bioRxiv) were searched for articles describing psychological/behavioral complications in children/adolescents with/without pre-existing behavioral abnormalities and their caregivers related to the COVID-19 pandemic. Only original articles with/without comparator arms and a minimum sample size of 50 were included in the analysis. The pooled estimate of various psychological/behavioral problems was calculated using a random-effect meta-analysis. RESULTS: Fifteen studies describing 22 996 children/adolescents fulfilled the eligibility criteria from a total of 219 records. Overall, 34.5%, 41.7%, 42.3% and 30.8% of children were found to be suffering from anxiety, depression, irritability and inattention. Although the behavior/psychological state of a total of 79.4% of children was affected negatively by the pandemic and quarantine, at least 22.5% of children had a significant fear of COVID-19, and 35.2% and 21.3% of children had boredom and sleep disturbance. Similarly, 52.3% and 27.4% of caregivers developed anxiety and depression, respectively, while being in isolation with children. CONCLUSION: Anxiety, depression, irritability, boredom, inattention and fear of COVID-19 are predominant new-onset psychological problems in children during the COVID-19 pandemic. Children with pre-existing behavioral problems like autism and attention deficit hyperactivity disorder have a high probability of worsening of their behavioral symptoms.