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SCN2A mutations have been identified in various encephalopathy phenotypes, ranging from benign familial neonatal-infantile seizure (BFNIS) to more severe forms of epileptic encephalopathy such as Ohtahara syndrome or epilepsy of infancy with migrating focal seizure (EIMFS). Thus far, no particularly effective treatment is available for severe epileptic encephalopathy caused by SCN2A mutations in children. We present the case of a boy who developed seizures on the third day of life and received a diagnosis of EIMFS based on his clinical presentations and electroencephalography reports. Antiepileptic drugs, namely oxcarbazepine, phenytoin, valproate, levetiracetam, and clonazepam, as well as adrenocorticotropic hormone therapy failed to reduce the severity of the seizures. Seizure pattern changed to infantile spasm with extensor thrust since 5 months of age. A ketogenic diet consisting of a medium-chain triglyceride recipe was introduced at 8 months of age and the seizures were resolved in the following 10 months. A de novo mutation in SCN2A (c.573G > T; p.W191C) was proven through next-generation sequencing.

Febrile seizure (FS) is the most common type of convulsion in infants and young children. The occurrence of FS in a subset of children with febrile illness suggested genetic factors may have an important effect on the predisposition of the disease. Using targeted next generation sequencing (NGS), a novel splicing variation (NM_198903.2:c.1249-1G>T) was identified in the γ-aminobutyric acid type A (GABA-A) receptor γ2 subunit (GABRG2) gene of a FS patient. To investigate possible association of FS with single nucleotide polymorphisms (SNPs) in prostaglandin-endoperoxide synthase-2 (prostaglandin G/H synthase-2; PTGS2/cyclooxygenase-2; COX2) gene involving in thermoregulatory pathway, eight SNPs, rs689465, rs689466, rs20417, rs13306038, rs201931599, rs689470, rs4648306 and rs4648308, along with 2 previously reported variations in IL1RN (86-bp VNTR) and IL10 (rs1900872) were genotyped and utilized for case-control association studies on 35 FS and 31 non-FS controls. A single SNP (rs689466) localized at 5'-1192 of the PTGS2 gene exhibited significant association with FS (p=0.045) based on case-control allelic association analyses. A significant decrease in the frequency of the G allele in FS (0.357) was observed compared to that in controls (0.536) with an estimated odds ratio (OR) of 0.48 (95% CI, 0.23-0.99) for the G versus A allele. Using case-control genotypic association analysis, the -1192 A allele is most likely to confer susceptibility to FS by a recessive action model (p=0.045, pointwise empirical p value (EMP1)=0.049). The association of SNPs in PTGS2, in addition to IL6, IL-6 receptor (IL6R) and prostaglandin E receptor 3 (PTGER3) in prior reports, with FS suggests their possible action in concert to modulate phenotypes in FS as well as the involvement of thermoregulatory pathway in pathogenesis of FS.

Background X-linked adrenoleukodystrophy is caused by a defective peroxisomal membrane transporter, ABCD1, responsible for transporting very-long-chain fatty acid substrate into peroxisomes for degradation. The main biochemical defect, which is also one of the major diagnostic hallmarks, of X-linked adrenoleukodystrophy is the accumulation of saturated very-long-chain fatty acids in all tissues and body fluids. Methods Direct and reverse-transcribed polymerase chain reactions followed by DNA sequencing-based mutational analyses were performed on one Taiwanese and three Malaysian X-linked adrenoleukodystrophy families. Results A novel splicing donor site mutation (c.1272+1g>a) was identified in a Taiwanese X-linked adrenoleukodystrophy patient, resulting in a deletion of 121 bp and a premature stop codon (p.Val425fs*92) in messenger-RNA transcript. This deletion is caused by the activation of a cryptic splicing donor site in exon 4 of the ABCD1 gene, which is consistent with the prediction by several online algorithms. In addition, three previously described missense mutations (c.965T>C, c.1978C>T, and c.2006A>G), leading to aberrant ABCD1 of p.Leu322Pro, p.Arg660Trp, and p.His669Arg, were also identified in Malaysian probands. Conclusions This is the first report to unveil unequivocally that cryptic splicing-induced aberrant messenger-RNA carrying an internal frameshift deletion results from an intronic mutation in the ABCD1 gene. Furthermore, a polymorphism in intron 9 (c.1992-32c/t; refSNP: rs4898368) of the ABCD1 gene was commonly observed in both Taiwanese and Malaysian populations.

X-linked adrenoleukodystrophy is a neurodegenerative disorder with highly variable clinical presentation, including the childhood cerebral form, adult form adrenomyeloneuropathy, and Addison disease. The biochemical hallmark of the disorder is the accumulation of saturated very long chain fatty acids in all tissues and body fluids. This accumulation results from mutations in the ABCD1 gene localized to Xq28. Using polymerase chain reaction and direct sequencing of deoxyribonucleic acid, we identified five novel mutations, including a microdeletion (1624 del ATC), a splicing site mutation (intervening sequence 1 [IVS1] -2a>c), and three missense mutations (1172 T>C, 1520 G>A, and 1754 T>C), from Taiwanese kindred with X-linked adrenoleukodystrophy. A polymorphism involving a single nucleotide deletion in the intervening sequence 5 (IVS5 -6 del c) of the ABCD1 gene, previously misattributed as a mutation in the Chinese population, was also identified. The dinucleotide deletion (1415 del AG) mutation common in Japan and Western countries was not found as frequently in the Chinese and Taiwanese populations. Instead, a higher mutation frequency was observed in exon 6 of the ABCD1 gene among Japanese, Chinese, and Taiwanese kindred with X-linked adrenoleukodystrophy, representing a potential mutational hotspot for future mutational screening among these Asian populations.

Agyria-pachygyria complex is a disorder of neuronal migration and organization. Patients suffer either motor or intellectual retardation. We report our experiences of 10 patients with agyria-pachygyria complex and evaluate their clinical features, electroencephalography, and evoked potentials. Of nine electroencephalography examinations, five patients demonstrated characteristically high-amplitude fast activity. One of nine patients had an abnormal brainstem auditory-evoked potential. Three of seven patients had abnormal goggled visual-evoked potential. Six patients received somatosensory-evoked potential examinations, and five of these were abnormal, including four with prolonged central conduction times. Of the 10 patients, eight survived with variable intellectual and motor retardation; two died of sepsis. Patients with grades 1-4 agyria-pachygyria had high incidences of somatosensory-evoked potential abnormalities and also suffered worse neurologic outcomes. Normal brainstem auditory-evoked potential but abnormal cortical somatosensory-evoked potential components and prolonged central conduction time in these patients indicate that agyria-pachygyria is a supratentorial disease. We conclude that somatosensory-evoked potential examination is supplemental to neuroimaging in predicting the neurologic prognosis of patients with agyria-pachygyria.

An 8-year-old female was diagnosed with Miller-Dieker syndrome with typical facial presentation. Brain magnetic resonance imaging disclosed lissencephaly, and chromosome study revealed 17p13.3 deletion. She developed infantile spasms at an early age, and her seizures were poorly controlled by multiple antiepileptics. Recurrent urinary tract infections were diagnosed during routine out-patient department follow-up. Urodynamic study disclosed a neurogenic bladder. Spinal magnetic resonance imaging revealed a tethered cord resulting from tight filum terminale, and untethering surgery was performed. Four months after the surgery, repeated urine cultures indicated that she was free from the urinary tract infection. Urodynamic study after untethering surgery demonstrated improved compliance of the urinary bladder.