SCN2A mutation is associated with infantile spasms and bitemporal glucose hypometabolism.

BACKGROUND: Genetic mutations play a crucial role in the etiology of cryptogenic infantile spasms, but the cause is still unknown in a significant proportion of patients. Whole exome sequencing technology shows great promise in identifying genetic causes of infantile spasms. METHODS: In this study whole exome sequencing was performed with 2-deoxy-2-((18)F)fluoro-d-glucose positron emission tomography scan of an infant boy with infantile spasms. Exome sequencing was also performed in the parents to identify any de novo mutations. RESULTS: The positron emission tomography scan showed a pattern of bilateral symmetric temporal lobe glucose hypometabolism. A total of 8171 nonsynonymous variants were identified in the child. Despite the large number of nonsynonymous variants, there was only a single de novo missense mutation in SCN2A in the child (NCBI hg19 assembly, position: Chr2:166234116, K1422E). Subsequent Sanger sequencing confirmed the de novo status of this variant. This mutation has never been reported in 6500 individuals of the exome variant server database. Similarly, this variant is not reported in the Online Mendelian Inheritance in Man Database or the Human Gene Mutation Database. It has previously been shown that SCN2A mutations are associated with hippocampal hyperexcitability. Therefore, this study indicates that infantile spasms and bitemporal hypometabolism in this patient might have been caused by hippocampal hyperexcitability due to SCN2A mutation. CONCLUSIONS: The simultaneous presence of an SCN2A mutation and bitemporal hypometabolism in this patient with infantile spasms suggests a plausible hippocampal origin. However, additional mechanistic and clinical studies are required to validate this link.

Infantile spasms are associated with abnormal copy number variations.

The authors tested the hypothesis that de novo copy number variations (CNVs) implicated in known genomic disorders ("pathogenic CNVs") are significant predisposing factors of infantile spasms. The authors performed a genome-wide analysis of single-nucleotide polymorphism genotyping microarray data to identify the role of de novo/known pathogenic large CNVs in 13 trios of children affected by infantile spasms. A rare, large (4.8 Mb) de novo duplication was detected in the 15q11-13 region of 1 patient. In addition, 3 known pathogenic CNVs (present in the patient as well as 1 of the parents) were detected in total. In 1 patient, a known pathogenic deletion was detected in the region of 2q32.3. Similarly, in 1 other patient, 2 known pathogenic deletions in the regions of 16p11.2 and Xp22.13 (containing CDKL5) were detected. These findings suggest that some specific pathogenic CNVs predispose to infantile spasms and may be associated with different phenotypes.

Longitudinal myelitis, aseptic meningitis, and conus medullaris infarction as presenting manifestations of pediatric systemic lupus erythematosus.

A healthy boy developed subacutely progressive quadriparesis, complicated by sudden paraplegia, fever, and meningeal signs, diagnosed as longitudinal myelitis, aseptic meningitis, and conus medullaris infarction and identified as the presenting manifestations of neuropsychiatric systemic lupus erythematosus. Rapid expansion of the conus on serial neuroimaging led to emergent decompressive laminectomy and cord biopsy showing vasculitis and cord infarction. The patient had partial recovery after treatment with high-dose steroids. Increased vigilance is required when pediatric patients develop a similar subacute presentation on the ground of active systemic lupus erythematosus because it may herald the onset of a catastrophic neurological syndrome.