Pediatric neurology最新文献

Background: Early infantile epileptic encephalopathy (EIEE) is a severe subtype of developmental and epileptic encephalopathies, characterized by early-onset, refractory seizures and associated with progressive psychomotor impairment, intellectual disability, and increased early mortality. In this cohort study, we evaluated patients diagnosed with 34 distinct EIEE subtypes over a 3-year period. In addition, we identified novel founder variants in unrelated patients from the Khorasan Razavi region in northeastern Iran.

Methods: Clinical assessments were performed by specialists. All affected individuals experienced seizures with onset before one year of age. Global developmental delay and intellectual disability were diagnosed according to standard clinical criteria and evaluated by pediatric neurologists. Genomic DNA was extracted from peripheral blood samples for whole-exome sequencing, with candidate variants subsequently validated by Sanger sequencing.

Results: We identified a total of 61 genetic variants associated with 34 distinct EIEE subtypes in 65 unrelated families. Of these, 38 variants (62.3%) were novel, whereas 23 variants (37.7%) had been previously reported. Notably, recurrent founder variants were observed among patients originating from specific geographic regions. Overall, 44 variants (72.13%) were classified as pathogenic or likely pathogenic, while 17 variants (27.87%) were categorized as variant of uncertain significance.

Conclusions: This study highlights the substantial genetic heterogeneity of EIEE in an underrepresented region, the Khorasan Razavi Province, with a high proportion of novel and founder variants. This study underscores the limitations of gene panels and supports the use of comprehensive genomic techniques, such as whole-exome sequencing, for early and accurate diagnosis.

Background: The purpose of this research is to study the neurological consequences of infantile vitamin B12 deficiency on the developing brain.

Methods: A prospective cohort study was done in consecutive children with Infantile B12 deficiency. Clinical evaluation, developmental assessment, blood investigations, and a magnetic resonance imaging (MRI) of the brain were performed at baseline and after therapy with injectable vitamin B12.

Results: Among 141 children (median age-13 months), developmental delay was observed in 131 (93%), and 79 (56%) had regression. Eighty (57%) babies had head circumference of < -2 Z score. At baseline, the MRI of the brain was abnormal in 137 (97.2%), showing thinning of corpus callosum (n = 133, 94.3%), cerebral cortical atrophy (n = 128, 90.8%), cerebellar atrophy (n = 126, 89.4%), atrophy of midbrain (n = 81, 57.4%) and pons (n = 78, 55.3%). A follow-up MRI done in 98 (69.5%) showed 66 (67%) had one or more residual abnormalities. The baseline full-scale developmental quotient was 22 (interquartile range: 13-30), while the follow-up full-scale developmental quotient score was 47.5 (interquartile range: 42.5-55). Seventy-nine (67.5%) had a follow-up developmental quotient of less than 50, implying moderate to severe developmental retardation.

Conclusions: Despite therapy, children affected by the infantile B12 deficiency syndrome have significant lasting effects on the brain, evident as poor head growth, developmental deficits, and residual brain imaging changes.