Genetic and phenotypic heterogeneity suggest therapeutic implications in SCN2A-related disorders.

Mutations in SCN2A, a gene encoding the voltage-gated sodium channel Nav1.2, have been associated with a spectrum of epilepsies and neurodevelopmental disorders. Here, we report the phenotypes of 71 patients and review 130 previously reported patients.

Obstructive sleep apnea in children with cerebral palsy and epilepsy.

Aim: To examine the risk of obstructive sleep apnea (OSA) in children with cerebral palsy (CP) and/or epilepsy.

Method: This cross-sectional study employs the Pediatric Sleep Questionnaire (PSQ), the Gross Motor Function Classification System (GMFCS), and chart review to identify symptoms of OSA in children presenting to a multi-specialty pediatric healthcare institution.

Results: Two-hundred and fifteen patients were grouped into those with epilepsy (n=54), CP (n=18), both (n=55), and neither (comparison group, n=88).

Whole-Exome Sequencing in the Clinic: Lessons from Six Consecutive Cases from the Clinician's Perspective.

Whole-exome sequencing (WES) is being used clinically to diagnose rare Mendelian disorders, especially when standard tests have failed. The diagnostic yield from WES is reported to be ∼15-30%; however, data regarding the clinical utility and interpretative challenges from the clinician's perspective are lacking. Here, we present a series of the first 6 unselected consecutive cases seen over a period of 6 months where WES was employed in clinical labs via trio-based testing (proband and parents).

Dravet syndrome and parent associations: the IDEA League experience with comorbid conditions, mortality, management, adaptation, and grief.

The advent of social networking via the Internet and the commercial availability of tests for SCN1A mutations permitted the rapid development and growth of parent-led associations that provide advocacy and support, as well as promote education and research regarding Dravet syndrome (DS) in the last 10 years. The International Dravet syndrome Epilepsy Action League (IDEA League) is a partnership of parents and professionals united in the purpose of creating greater awareness and understanding of DS. In 2004, parents in the IDEA League support network began to collect data from families about their children with DS in order to investigate observations that, in addition to epilepsy, many of the children seemed to share similar problems.

Molecular and clinical genetics of mitochondrial diseases due to POLG mutations.

Mutations in the POLG gene have emerged as one of the most common causes of inherited mitochondrial disease in children and adults. They are responsible for a heterogeneous group of at least 6 major phenotypes of neurodegenerative disease that include: 1) childhood Myocerebrohepatopathy Spectrum disorders (MCHS), 2) Alpers syndrome, 3) Ataxia Neuropathy Spectrum (ANS) disorders, 4) Myoclonus Epilepsy Myopathy Sensory Ataxia (MEMSA), 5) autosomal recessive Progressive External Ophthalmoplegia (arPEO), and 6) autosomal dominant Progressive External Ophthalmoplegia (adPEO). Due to the clinical heterogeneity, time-dependent evolution of symptoms, overlapping phenotypes, and inconsistencies in muscle pathology findings, definitive diagnosis relies on the molecular finding of deleterious mutations.

Gabapentin successfully manages chronic unexplained irritability in children with severe neurologic impairment.

Neurologically impaired children have an increased frequency of recurrent pain and irritability that persist in some despite comprehensive evaluation and management of possible pain sources. We hypothesized that visceral hyperalgesia was a source of chronic unexplained irritability and report the outcome of gabapentin treatment in 9 severely neurologically impaired children. Caregivers reported marked improvement after treatment ranging from 3 months to 3 years.

Rapid infusion of sodium valproate in acutely ill children.

The purpose of this study was to investigate the clinical safety of sodium valproate and total and unbound valproic acid plasma concentrations after rapid infusion in hospitalized, acutely ill children. Four children (5-15 years) completed the study. Sodium valproate doses (8.