The utility of exome sequencing in diagnosing pediatric neurodevelopmental disorders in a highly consanguineous population.

Exome sequencing (ES) has been utilized in diagnosing children with neurodevelopmental manifestations, this study aimed to investigate the utility of ES in children within a highly consanguineous population that presented with neurodevelopmental complaints. A retrospective chart review was performed for 405 children with neurodevelopmental complaints who have had ES and were evaluated in multiple centers in the United Arab Emirates over a four-year period. Within the cohort of 405 children, consanguinity was reported in 35% (144/405). The primary clinical presentations were developmental delay/cognitive impairment, distinctive facial features, hypotonia, seizures, and weakness. The diagnostic yield was 57% (231/405). Novel variants were identified in 54% (125/231) of positive cases. Within the positive cases, specific treatment was available in 6% (13/231) and copy number variants (CNV) were reported in 3% (8/231) of cases. In eight children, variants in genes that have not yet been linked to human disease that could potentially be the cause of the observed phenotype "candidate genes" were identified. ES was utilized effectively within this cohort with a high diagnostic yield and through the identification of novel gene variants, CNVs, candidate genes and secondary findings as well as the alteration of the treatment plan in cases where treatment was available.

Anti-N-methyl-d-aspartate Receptor Encephalitis: A Case Series and Review of the Literature.

Anti-NMDAR (N-methyl-d-aspartate receptor) encephalitis is a potentially severe form of encephalitis associated with antibodies against NR1 and NR2 subunits of the NMDAR. Anti-NMDAR encephalitis is a treatable cause of encephalitis. An underlying tumor should be actively looked for as this is also considered to be a paraneoplastic syndrome. We report two children with anti-NMDAR encephalitis with a literature review of current evidence in diagnosing and managing this rare condition. Resection of the tumor, glucocorticoids, intravenous immunoglobulin, and plasma exchange often result in improvement, usually within four weeks. Outcome corresponds with the rapidity of commencing appropriate treatment.

Prolonged video-EEG in identifying paroxysmal nonepileptic events in children with epilepsy: a useful tool.

PURPOSE: Habitual events, behaviors, and nonepileptic events can be easily confused with epileptic seizures in children in the absence of clear description and can be challenging, even for an experienced clinician. The aim was to report on the usefulness of adding video-EEG to routine EEG studies of infants and children with frequent atypical paroxysmal events. METHODS: A retrospective analysis of video-EEG carried over a 2-year period in a tertiary pediatric neurology center. Outcomes were classified as: "conclusive epileptic," "conclusive nonepileptic," "unremarkable," and "inconclusive." RESULTS: Forty-four children (M:F 19:25) with an age range of 1 to 15 years (mean: 7 years, median: 8.5 years) were analyzed. Thirty (68%) children had successful epilepsy classification. A diagnosis of a specific nonepileptic event was reached in 55% of cases. Antiepileptic drugs were discontinued completely in 8 patients (20%), and the total number of antiepileptic drugs was reduced in 13 others (33%). CONCLUSIONS: Paroxysmal nonepileptic events can cause diagnostic confusion, particularly in children with developmental delay, epilepsy (especially refractory epilepsy), or those with previous "abnormal" EEG. Accurate diagnosis can be reached in the majority of cases using prolonged video-EEG monitoring.

Abnormal levels of serum anti-elastin antibodies in patients with symptomatic carotid stenosis.

BACKGROUND AND OBJECTIVE: A correlation between the levels of antibodies to alpha-elastin (alpha-AEAb) and tropoelastin (tropo-AEAb) and the corresponding peptide concentration is found in human serum in health and disease. Serum elastin peptide and anti-elastin antibodies (AEAb) levels are age-related and vary with the stages of atherosclerotic vascular damage. This study aims to determine if elastin metabolism (assessed by the ratio of tropo-AEAb to alpha-AEAb) differs in patients with symptomatic carotid stenosis versus subjects with asymptomatic stenosis. PATIENTS AND METHODS: Alpha-AEAb and tropo-AEAb were measured by ELISA in blood sera of 65 patients with ultrasound verified high-grade symptomatic carotid stenosis (resulting in stroke 1-7 days before measurement) compared to 51 patients with asymptomatic stenosis. RESULTS: Serum anti-alpha-elastin IgG levels are extremely increased in symptomatic versus asymptomatic carotid stenosis. The ratio of tropo-AEAb (reflecting elastin synthesis) to alpha-AEAb (a function of elastin degradation) was 3.7 in symptomatic stenosis versus 14.2 in asymptomatic stenosis (p<0.001). CONCLUSIONS: There is a significant difference in elastin metabolism in patients with symptomatic carotid stenosis versus asymptomatic stenosis. The ratio of tropo-AEAb to alpha-AEAb as an index of elastin synthesis/degradation proves useful in investigation of atherosclerotic lesions and may represent a new immunologic marker for carotid plaque destabilization.

Speech and language delay in two children: an unusual presentation of hyperthyroidism.

BACKGROUND: Hyperthyroidism is rare in pre-school children. Untreated, it can have a profound effect on normal growth and development, particularly in the first 2 years of life. Although neurological manifestations of dysthyroid states are well known, specific expressive speech and language disorder as a presentation of hyperthyroidism is rarely documented. METHODS: Case reports of two children with hyperthyroidism presenting with speech and language delay. RESULTS: We report two pre-school children with hyperthyroidism, who presented with expressive speech and language delay, and demonstrated a significant improvement in their language skills following treatment with anti-thyroid medication. CONCLUSIONS: Hyperthyroidism must be considered in all children presenting with speech and language difficulties, particularly expressive speech delay. Prompt recognition and early treatment are likely to improve outcome.

TUBA1A mutation-associated lissencephaly: case report and review of the literature.

Lissencephaly is a disorder of neuronal migration resulting in abnormal cerebral cortical sulcation and gyration. Affected children present with microcephaly, developmental delay, and early-onset epileptic seizures. Recently, de novo missense mutations in the tubulin α-1A (TUBA1A) gene were identified as causing a distinctive radiologic phenotype comprising of posteriorly predominant lissencephaly with dysgenetic corpus callosum, cerebellar and brainstem hypoplasia, and more recently, polymicrogyria. We describe a 14-month-old girl with TUBA1A mutation-associated lissencephaly, and summarize the clinical and neuroradiologic findings of 19 cases in the literature.