Importance of targeted next-generation sequencing in pediatric patients with developmental epileptic encephalopathy
Savaş Bariş1, Serkan Kırık2, Özgür Balasar3
1Aydın Obstetrics and Gynecology Hospital, Genetic Diseases Diagnosis Center - Aydın, Turkiye.
Insights
Genetic testing identified various mutations in children with refractory epilepsy and global developmental delay. Understanding the genetic cause is crucial for diagnosis, counseling, and potential future treatments.
Area of Science:
- Pediatric Neurology
- Clinical Genetics
- Molecular Diagnostics
Background:
- Childhood epilepsy affects 300-600 per 100,000 children.
- Associated with refractory epilepsies, global developmental delay, and epileptic encephalopathies.
- These conditions cause significant cognitive and behavioral disorders.
Purpose of the Study:
- To investigate the genetic underpinnings of refractory epilepsy with global developmental delay.
- To identify specific gene mutations in pediatric patients diagnosed with epileptic encephalopathy.
Main Methods:
- Retrospective cohort study.
- Inclusion of patients from July 2018 to July 2021 at Aydın 7 Maternity and Children's Hospital.
- Targeted next-generation sequencing for molecular genetics analysis.
Main Results:
- Multiple mutations were detected in genes including SCN1A (4), TBC1D24 (4), ALDH7A1 (3), CACNA1A (3), KCNQ2 (3).
- Other identified mutations were in AARS, CTNNB1, DCX, DBH, DOCK7, FOLR1, GABRB3, GCH1, VGRIN2B, GUF1, KCNT1, NECAP1, PCDH19, PNPO, SCN8A, SCN9A, SLC25A22, SLC2A1, SPTAN1, SZT2, TH.
- Mutations were identified in three patients via next-generation sequencing.
Conclusions:
- Gene panels improve diagnostic capabilities for childhood epilepsy.
- Significant genetic and phenotypic variability exists, with some disorders remaining unidentified.
- Elucidating genetic etiology is essential for genetic counseling and therapeutic development.
Objective:
Childhood epilepsy is a common neurological disorder with a prevalence of 300-600 cases per 100,000 people. It is associated with refractory epilepsies, global developmental delay, and epileptic encephalopathies, causing epileptic syndromes characterized by cognitive and behavioral disorders.
Methods:
In this retrospective cohort study, patients with refractory epilepsy and global developmental delay, defined as epileptic encephalopathy, who applied to the Aydın 7Maternity and Children's Hospital Genetic Diagnosis Center and were followed in the pediatric neurology clinic of our hospital, between July 2018 and July 2021, were included.
Results:
Targeted next-generation sequencing molecular genetics results were reviewed, and 3 ALDH7A1, 1 AARS, 3 CACNA1A, 1 CTNNB1, 1 DCX, 2 DBH, 2 DOCK7, 1 FOLR1, 2 GABRB3, 2 GCH1, 1 VGRIN2B, 1 GUF1, 3 KCNQ2, 2 KCNT1, 1 NECAP1, 1 PCDH19, 1 PNPO, 1 SCN8A, 1 SCN9A, 4 SCN1A, 2 SLC25A22, 1 SLC2A1, 2 SPTAN1, 2 SZT2, 4 TBC1D24, 2 TH, and 1 PCDH19 (X chromosome) mutations were detected in three of the patients using the next-generation sequencing method.
Conclusion:
Although the development of gene panels aids in diagnosis, there are still unidentified disorders in this illness category, which is highly variable in genotype and phenotype. Understanding the genetic etiology is vital for genetic counseling and, maybe, the future development of remedies for the etiology.
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