Utility of genetic testing in children with developmental and epileptic encephalopathy (DEE) at a tertiary hospital in South Africa: A prospective study

Essajee, Farida; Urban, Michael; Smit, Liezl; Wilmshurst, Jo M; Solomons, Regan; Toorn, Ronald van; Moosa, Shahida

doi:10.1016/j.seizure.2022.09.001

Cited by 13 publications

(7 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An increasing number of single-gene disorders are being recognized as being associated with an IESS phenotype [ 10 , 12 , 13 , 70 , 71 , 72 , 73 , 74 , 75 ]. Discussion of all attributable genes is beyond the scope of this review; we will focus on a sample of those which have been most commonly reported in the literature.…”

Section: Spectrum Of Genetic Aetiologies Of Iessmentioning

confidence: 99%

“…Discussion of all attributable genes is beyond the scope of this review; we will focus on a sample of those which have been most commonly reported in the literature. Overall, some of the genes most frequently associated with IESS include pathogenic variants in TSC1 , TSC2 , CDKL5 , ARX , KCNQ2 , STXBP1 , SCN2A and SCN8A , amongst others, although exact incidences of variants fluctuate between individual cohort studies [ 10 , 12 , 13 , 70 , 71 , 72 , 73 , 74 ]. Moreover, genes associated with IESS have various patterns of inheritance, including de novo or autosomal dominant, autosomal recessive and X-linked patterns [ 10 , 12 , 13 , 70 , 71 , 72 , 73 , 74 ].…”

Section: Spectrum Of Genetic Aetiologies Of Iessmentioning

confidence: 99%

See 1 more Smart Citation

Genetic Advancements in Infantile Epileptic Spasms Syndrome and Opportunities for Precision Medicine

Snyder,

Jain,

RamachandranNair

et al. 2024

Genes

View full text Add to dashboard Cite

Infantile epileptic spasms syndrome (IESS) is a devastating developmental epileptic encephalopathy (DEE) consisting of epileptic spasms, as well as one or both of developmental regression or stagnation and hypsarrhythmia on EEG. A myriad of aetiologies are associated with the development of IESS; broadly, 60% of cases are thought to be structural, metabolic or infectious in nature, with the remainder genetic or of unknown cause. Epilepsy genetics is a growing field, and over 28 copy number variants and 70 single gene pathogenic variants related to IESS have been discovered to date. While not exhaustive, some of the most commonly reported genetic aetiologies include trisomy 21 and pathogenic variants in genes such as TSC1, TSC2, CDKL5, ARX, KCNQ2, STXBP1 and SCN2A. Understanding the genetic mechanisms of IESS may provide the opportunity to better discern IESS pathophysiology and improve treatments for this condition. This narrative review presents an overview of our current understanding of IESS genetics, with an emphasis on animal models of IESS pathogenesis, the spectrum of genetic aetiologies of IESS (i.e., chromosomal disorders, single-gene disorders, trinucleotide repeat disorders and mitochondrial disorders), as well as available genetic testing methods and their respective diagnostic yields. Future opportunities as they relate to precision medicine and epilepsy genetics in the treatment of IESS are also explored.

show abstract

Section: Spectrum Of Genetic Aetiologies Of Iessmentioning

confidence: 99%

Section: Spectrum Of Genetic Aetiologies Of Iessmentioning

confidence: 99%

Genetic Advancements in Infantile Epileptic Spasms Syndrome and Opportunities for Precision Medicine

Snyder,

Jain,

RamachandranNair

et al. 2024

Genes

View full text Add to dashboard Cite

show abstract

“…Certain genetic mutations can provide therapeutic options that may be more effective for a particular patient. Based on current clinical evidence, some precision medicine strategies for epilepsy have been proposed [ 66 , 67 ]. However, early genetic testing is only the first step in the precise approach; functional testing is also required to determine pathogenicity and explore the fundamental functional impact, such as in the case of the SCN1A variant [ 68 , 69 , 70 ].…”

Section: Discovery and Clinical Application Of Genetic Testing For Deesmentioning

confidence: 99%

Genetic Testing in Children with Developmental and Epileptic Encephalopathies: A Review of Advances in Epilepsy Genomics

et al. 2023

View full text Add to dashboard Cite

Advances in disease-related gene discovery have led to tremendous innovations in the field of epilepsy genetics. Identification of genetic mutations that cause epileptic encephalopathies has opened new avenues for the development of targeted therapies. Clinical testing using extensive gene panels, exomes, and genomes is currently accessible and has resulted in higher rates of diagnosis and better comprehension of the disease mechanisms underlying the condition. Children with developmental disabilities have a higher risk of developing epilepsy. As our understanding of the mechanisms underlying encephalopathies and epilepsies improves, there may be greater potential to develop innovative therapies tailored to an individual’s genotype. This article provides an overview of the significant progress in epilepsy genomics in recent years, with a focus on developmental and epileptic encephalopathies in children. The aim of this review is to enhance comprehension of the clinical utilization of genetic testing in this particular patient population. The development of effective and precise therapeutic strategies for epileptic encephalopathies may be facilitated by a comprehensive understanding of their molecular pathogenesis.

show abstract

“…Due to the pleiotropic nature of STXBP1, it has become one of the most identified variants of concern, with a recent study of 150 children with EIEE identifying STXBP1 variants in 6% of infantile onset epilepsy patients, and 10% of neonatal onset epileptic encephalopathy [3]. It has often been identified as one of the top five causative genes in a variety of genetic screening studies including infantile spasms [4][5][6][7], DEE [8][9][10], EIEE [11], and a combination of ID, GDD, and autism spectrum disorder [12]. Due to its importance within the cell and its role in clinical disease, STXBP1 has become an area of research interest.…”

Section: Introductionmentioning

confidence: 99%

STXBP1-Related Disorders: Clinical Presentation, Molecular Function, Treatment, and Future Directions

Freibauer,

Wohlleben,

Boelman

2023

Genes

View full text Add to dashboard Cite

In recent years, the affordability and availability of genetic testing have led to its increased use in clinical care. The increased frequency of testing has led to STXBP1 variants being identified as one of the more common variants associated with neurological disorders. In this review, we aim to summarize the common clinical phenotypes associated with STXBP1 pathogenic variants, provide an overview of their known natural history, and discuss current research into the genotype to phenotype correlation. We will also provide an overview of the suspected normal function of the STXBP1-encoded Munc18-1 protein, animal models, and experimental techniques that have been developed to study its function and use this information to try to explain the diverse phenotypes associated with STXBP1-related disorders. Finally, we will explore current therapies for STXBP1 disorders, including an overview of treatment goals for STXBP1-related disorders, a discussion of the current evidence for therapies, and future directions of personalized medications for STXBP1-related disorders.

show abstract

Utility of genetic testing in children with developmental and epileptic encephalopathy (DEE) at a tertiary hospital in South Africa: A prospective study

Cited by 13 publications

References 50 publications

Genetic Advancements in Infantile Epileptic Spasms Syndrome and Opportunities for Precision Medicine

Genetic Advancements in Infantile Epileptic Spasms Syndrome and Opportunities for Precision Medicine

Genetic Testing in Children with Developmental and Epileptic Encephalopathies: A Review of Advances in Epilepsy Genomics

STXBP1-Related Disorders: Clinical Presentation, Molecular Function, Treatment, and Future Directions

Contact Info

Product

Resources

About