Clinical ObservationsFolinic Acid Responsive Epilepsy in Ohtahara Syndrome Caused by STXBP1 Mutation
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)
- et al.
Early-onset epileptic encephalopathies: Ohtahara syndrome and early myoclonic encephalopathy
Pediatr Neurol
(2012) - et al.
Genes of early-onset epileptic encephalopathies: from genotype to phenotype
Pediatr Neurol
(2012) - et al.
Selective activation of cognate SNAREpins by Sec1/Munc18 proteins
Cell
(2007) - et al.
Epileptic and nonepileptic features in patients with early onset epileptic encephalopathy and STXBP1 mutations
Epilepsia
(2011) - et al.
De novo mutations in the gene encoding STXBP1 (MUNC18-1) cause early infantile epileptic encephalopathy
Nat Genet
(2008) - et al.
Clinical spectrum of early-onset epileptic encephalopathies associated with STXBP1 mutations
Neurology
(2010)
Cited by (19)
In vivo calcium imaging reveals disordered interictal network dynamics in epileptic stxbp1b zebrafish
2021, iScienceCitation Excerpt :Many are associated with single gene mutations (Howard and Baraban, 2017). For example, childhood STXBP1 (syntaxin-binding protein 1, also known as MUNC18-1) disorder is a haploinsufficiency associated with heterogeneous epilepsy phenotypes (Stamberger et al., 2016): early infantile epileptic encephalopathy (EIEE; also known as Ohtahara syndrome) (Saitsu et al., 2010; Tso et al., 2014), infantile spasms (also known as West syndrome) (Barcia et al., 2014; Otsuka et al., 2010), Lennox-Gastaut syndrome (Epi4K Consortium et al., 2013), and Dravet syndrome (Carvill et al., 2014). Additionally, STXBP1 mutation can be associated with neurodevelopmental disorders without epilepsy (Hamdan et al., 2011; Stamberger et al., 2016).
Neonatal epilepsy genetics
2018, Seminars in Fetal and Neonatal MedicineCitation Excerpt :Clues to diagnosis include normal head size at birth and normal head growth, variable muscle tone at times with asymmetries, and movement disorders (chorea, dystonic posturing, tremors, or dyskinesia) starting as early as the neonatal period. Whereas there is not an established targeted therapy, there has been some suggestion of response to vigabatrin and at least two reports of response to leukovorin (one with low and one with normal CSF folate) [3,44]. In-frame deletions and duplications in the non-erythrocytic α-spectrin-1 (SPTAN1), coding for a protein involved in regulating stability of axonal structure, may cause early-onset West syndrome with spastic quadriplegia and progressive microcephaly with severe hypomyelination and developmental delays [45].
Loss-of-function mutations of STXBP1 in patients with epileptic encephalopathy
2016, Brain and DevelopmentCitation Excerpt :Subsequently, we identified novel STXBP1 mutations associated with Ohtahara syndrome and West syndrome in two unrelated patients [6]. Thereafter, many STXBP1 mutations have been reported [7–19]. Here, we report on the new results of our ongoing study of STXBP1 in patients with epileptic encephalopathy.
Benefits of folinic acid as coadjuvant therapy
2022, Medicina Interna de MexicoChildhood Epilepsy Syndromes
2022, Handbook of Pediatric Epilepsy