Possible role of SCN4A skeletal muscle mutation in apnoea during seizure

SCN4A gene mutations cause a number of neuromuscular phenotypes including myotonia. A subset of infants with myotonia‐causing mutations experience severe life‐threatening episodic laryngospasm with apnea. We have recently identified similar SCN4A mutations in association with sudden infant death syndrome. Laryngospasm has also been proposed as a contributory mechanism to some cases of sudden unexpected death in epilepsy (SUDEP). We report an infant with EEG‐confirmed seizures and recurrent apneas. Whole‐exome sequencing identified a known pathogenic mutation in the SCN4A gene that has been reported in several unrelated families with myotonic disorder. We propose that the SCN4A mutation contributed to the apneas in our case, irrespective of the underlying cause of the epilepsy. We suggest this supports the notion that laryngospasm may contribute to some cases of SUDEP, and implicates a possible shared mechanism between a proportion of sudden infant deaths and sudden unexpected deaths in epilepsy

A Novel splice-site mutation on the MLC1 gene leading to exon 9 skipping and megalencephalic leukoencephalopathy with subcortical cysts in a Turkish patient

Megalencephalic leukoencephalopathy (MLC) with subcortical cysts, also known as Van der Knaap disease (MIM #604004) is an autosomal recessive neurological disorder characterized by early onset macrocephaly, epilepsy, neurological deterioration with cerebellar ataxia and spasticity. An 8-month-old boy was admitted to our pediatric neurology clinic with macrocephaly. His brain magnetic resonance imaging (MRI) revealed bilateral, diffuse, symmetric structural white matter abnormalities, relatively sparing the cerebellum and bilateral subcortical temporal cysts. The diagnosis of Van der Knaap disease was suspected based on the clinical features and imaging findings and the genetic analysis revealed a novel homozygous c.768+2T>C mutation of the MLC1 gene. For determination of the novel splice-site mutation’s effect, cDNA amplification was performed. cDNA analysis showed that the splice-site c.768+2T>C mutation gave rise to exon 9 skipping

Glial fibrillary acidic protein (GFAP)-antibody in children with focal seizures of undetermined cause

Anti-neuronal antibodies that are related with autoimmune encephalitis syndromes may also be found in children with new onset seizures or chronic epilepsy. To unravel the significance of autoimmune astrocytopathy in epilepsy, we investigated serum antibody to glial fibrillary acidic protein (GFAP), another autoantigen described in autoimmune encephalitis with seizures, in 38 children with focal seizures of undetermined cause. GFAP antibody was screened with cell based assay and indirect immunohistochemistry and was found in two boys with normal brain MRI and unrevealing medical history prior to seizures. The 2-year-old boy had chronic treatment-resistant frontal lobe epilepsy. The 2.5-year-old boy had a single episode of focal seizures and remained seizure free thereafter in a follow-up period of 4 years. Nevertheless, he showed severe cognitive and language impairment. These results suggest that autoimmune astrocytopathy may be present in some epilepsy patients. Whether this immune response is a bystander effect generated by seizure-induced astrocytosis or directly involved in epileptogenesis needs to be further studied. © 2020, Belgian Neurological Society