Infantile Epileptic Spasm Syndrome : New Horizons In Genomic Era?

Administrator: Adam Numis & Ingrid Scheffer

Genetic testing in infantile epilepsies with respect to IESS.
Adam Numis

The diagnostic yield of genetic testing is advancing. With the advances afforded by next-generation sequencing, there are now more genes associated with IESS, with a diverse array of genetic mechanisms implicated. Targeted NGS-based epilepsy panels and whole exome sequencing (WES) analysis offer a diagnostic yield ranging from 10-48% in DEEs (Yuskaitis CJ et al., 2018). Genetic causes are increasingly recognized as an etiology of IESS. It is postulated that a genetic etiology of up to 41% of IESS patients. The step-based diagnostic approach is suggested to define the precise etiology of IESS (Wirrell EC et al.,2015). A cost-effective genetic workup is recommended for patients without specific etiology after initial clinical evaluation and neuroimaging. The diagnostic yield also depends on the population tested. The genetic landscape of IESS has been largely shaped by the rise of high throughput sequencing. To date, dozens of genes convincingly linked to IESS have been identified via the whole exome and  genome sequencing techniques.

Precision therapies: current and future perspectives
Ingrid Scheffer

Infantile epileptic spasms syndrome has a wide range of etiologies such as genetic, metabolic, and structural brain abnormalities (Wilmshurst JM et al., 2016). The diagnostic yield of next-generation sequencing technologies and genomic mapping provided more gene-named developmental encephalopathies in IESS. As a result of advances in the genetics of IESS, precision medicine provides hope for patients with IESS. Despite early treatment with standard regimens of hormone therapy and /or vigabatrin,most of the patients in the genetic-specific etiology group do not become seizure-free and have acognitive disability.  Children with IESS frequently experience drug-resistant seizures as well as developmental disabilities linked to cerebral epileptiform activity, therefore, there is an additional reason to utilize the molecular diagnostic findings to help guide treatment. Approaches based on precision medicine have the potential to significantly enhance the quality of life for children with IESS and their families. Currently, many genetic causes of IESS can be targeted for treatment, including genes encoding sodium channel subunits, tuberous sclerosis, and congenital metabolic disorders. Precision medicine may refer to more sensible selections of standard anti-seizure medications, repurposed therapies previously used for other indications, new chemicals, enzyme replacement, or gene therapy techniques (Myers KA et al., 2022)