Researchers from Japan presented the case of a patient with neonatal developmental and epileptic encephalopathy with movement disorders and arthrogryposis (NDEEMA) who had a novel missense variant of the SCN1A gene.
The team led by Kazuhiro Haginoya, MD, PhD, from the department of pediatric neurology, Miyagi Children’s Hospital, Sendai, Japan, also discussed the efficacy of sodium channel blockers to treat the disease.
The case is that of a girl aged 3 years who had various clinical features including arthrogryposis multiplex congenita, thoracic hypoplasia, thoracic scoliosis, and hyperekplexia.
Phenobarbital, levetiracetam, and carbamazepine treatment partially controlled her epileptic apnea. The most effective was carbamazepine in controlling epileptic apneic attacks and hyperekplexia.
The patient had a de novo SCN1A missense variant, c.5340G > A (p. Met1780Ile), and was diagnosed with neonatal onset SCN1A epileptic encephalopathy.
“Our findings indicate that some missense variants of SCN1A cause more deleterious phenotypes,” the researchers wrote, in a report that they published in the journal Brain and Development. “Further exploration of the phenotype–genotype relationship of SCN1A variants may lead to better pharmacological treatments and family guidance.”
Variants of SCN1A represent the archetypal channelopathy associated with several epilepsy syndromes including Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS).
Read more about Dravet syndrome
New epilepsy phenotypes have expanded recently from DS and genetic epilepsy with febrile seizures plus, to include familial hemiplegic migraine, epilepsy of infancy with migrating focal seizure, and early infantile SCN1A epileptic encephalopathy. The most severe phenotype caused by a gain-of-function variant of the SCN1A gene is NDEEMA.
The SCN1A gene found on chromosome 2 encodes the alpha subunit of the neuronal voltage-gated sodium channels, Nav1.1, which are predominantly found in the brain where they control the flow of sodium ions into cells. These channels are crucial for the transmission of nerve signals from one neuron to the other.
Reference
Okubo Y, Shibuya M, Nakamura H, et al. Neonatal developmental and epileptic encephalopathy with movement disorders and arthrogryposis: A case report with a novel missense variant of SCN1A. Brain Dev. 2023;11:S0387-7604(23)00110-9. doi:10.1016/j.braindev.2023.06.009
