Elsevier

Pediatric Neurology

Volume 50, Issue 2, February 2014, Pages 177-180
Pediatric Neurology

Clinical Observations
Folinic Acid Responsive Epilepsy in Ohtahara Syndrome Caused by STXBP1 Mutation

https://doi.org/10.1016/j.pediatrneurol.2013.10.006Get rights and content

Abstract

Background

Ohtahara syndrome is a severe condition with early onset of recurrent unprovoked seizures associated with abnormal electroencephalography and global developmental delay. Folinic acid–responsive seizures are treatable causes of Ohtahara syndrome, which is thought to be due to recessive mutations in the ALDH7A1 gene, resulting in deficiency of antiquitin.

Method

Here we report a girl with Ohtahara syndrome who exhibited transient folinic acid responsiveness but without evidence of antiquitin dysfunction.

Results

She was later found to have a known missense mutation (c.1439 C > T, p.P480 L) in exon 16 of the STXBP1 gene.

Conclusion

For infants presenting with Ohtahara syndrome with responsiveness to folinic acid and negative antiquitin deficiency analyses, genetic testing for other possible causative genes such as STXBP1 mutation is recommended.

Introduction

Ohtahara syndrome is a rare form of epilepsy characterized by intractable seizures within the first few weeks to months of life associated with poor developmental outcome. Infants acutely develop tonic spasms that can be either generalized or lateralized, can occur both singly or in clusters, and are independent of the sleep cycle.1 Causes of Ohtahara syndrome include structural brain anomalies, inborn errors of metabolism, genetic abnormalities, and unknown factors. Previous studies illustrated that genetic mutations play important pathogenic roles in developmental defects and monogenic mutations in genes involved in brain development or synaptic functions have been reported to be associated with Ohtahara syndrome.2

Prolonged or intractable seizures have detrimental effects on brain function; treatable vitamin-responsive causes of Ohtahara syndrome such as folinic acid responsive seizures should not be missed. It is widely believed that folinic acid–responsive seizures are identical to pyridoxine-dependent epilepsy because both conditions are caused by α-aminoadipic semialdealdehyde (α-AASA) deficiency with pathogenic mutations in the ALDH7A1 (antiquitin) gene. Here we report a case of Ohtahara syndrome with transient folinic acid responsiveness but without evidence of antiquitin dysfunction. The girl was later found to have a known STXBP1 mutation.

Section snippets

Case Report

We described a girl presenting with epileptic spasm soon after birth. The baby had nonconsanguineous parents and was born full term via normal vaginal delivery. At day 3 of life, she had a neonatal seizure, presenting as cluster of epileptic spasms that lasted for less than 2 minutes. Sepsis workup including blood culture, cerebrospinal fluid, viral studies, and C-reactive protein were all unremarkable. Ultrasound brain showed grade I intraventricular hemorrhage bilaterally with increased

Discussion

Ohtahara syndrome is a severe condition with early onset of recurrent unprovoked seizures associated with abnormal electroencephalography and global developmental delay.

Heterozygous mutations were first revealed in candidate gene encoding STXBP1 in four unrelated individuals with Ohtahara syndrome by Saitsu et al.4 after the discovery of a 2.0-Mb microdeletion at 9q33.3-q34.11 in a girl with Ohtahara syndrome by array-based comparative genomic hybridization. Further studies revealed association

References (12)

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