Genetic and Metabolic Etiologies of Epilepsy in Children
Abstract number :
1.112
Submission category :
12. Genetics / 12A. Human Studies
Year :
2024
Submission ID :
1282
Source :
www.aesnet.org
Presentation date :
12/7/2024 12:00:00 AM
Published date :
Authors :
Presenting Author: Muhammed Bayraktutan, MD – Boston Children's Hospital
Pelin Kiper, MD, PhD – Hacettepe University, Ihsan Dogramaci Children's Hospital
Ali Dursun, MD, PhD – Hacettepe University, Ihsan Dogramaci Children's Hospital
Ceren Günbey, MD – Hacettepe University, Ihsan Dogramaci Children's Hospital
Eda Ütine, MD, PhD – Hacettepe University, Ihsan Dogramaci Children's Hospital
Göknur Haliloğlu, MD – Hacettepe University, Ihsan Dogramaci Children's Hospital
Dilek Yalnızoğlu, MD – Hacettepe University, Ihsan Dogramaci Children's Hospital
Rationale: The concept of classifications in pediatric epilepsy is moving forward rapidly, parallel to access to molecular diagnostic tools. We aimed to retrospectively analyze the cross-sectional distribution of epilepsy etiologies at a tertiary referral center between January 2020 and December 2021, focusing on genetic and inherited metabolic disorders.
Methods: We reviewed demographic features, age at seizure onset, seizure type and frequency, comorbidities, family history, EEG and MRI abnormalities, and treatment in patients classified under genetic and inherited metabolic epilepsy.
Results: Within a cohort of 895 patients diagnosed with epilepsy, the etiologies were as follows: Structural (n=340; 38%), genetic (n=99; 11%), inherited metabolic (n=61; 7%), infectious (n=21; 2%), immune-related (n=15; 2%), and unknown (n=359; 40%). Genetic epilepsies constitute monogenic disorders (n=66; 67%), copy number variants (n=25; 25%), and chromosomal disorders (n=8, 8%). Out of 66 patients with monogenic disorders, 41 different genetic diagnoses were recorded. Pathogenic variants of SCN1A were the most common, with 15 patients affected. Inherited metabolic epilepsies were further subclassified into small molecule disorders (n=31; 50%), complex molecule disorders (n=15; 25%), and energy metabolism disorders (n=15; 25%). Variants affecting 51 different genes were identified in the group of metabolic epilepsies. The median age at seizure onset was 22 months and 9 months for genetic and metabolic epilepsies, respectively. Seizure onset within the first two years of life was ~70% within the genetic (n=70) and metabolic (n=44) groups. Early onset seizures, refractory epilepsy, abnormal neurologic examination findings, and developmental, cognitive/neuropsychiatric, and medical comorbidities were common features among both genetic and metabolic epilepsies. The prevalence of gastrointestinal (~35%) and respiratory (~20%) comorbidities was particularly notable in genetic and metabolic epilepsies. The consanguinity rate in genetic epilepsies was close to the consanguinity rate in our country (20%), whereas the metabolic group had a higher consanguinity rate (60%). The mortality rate was highest in the energy metabolism disorders subgroup of metabolic epilepsies. Among patients with available imaging data, abnormalities were found in 75% (64/85) of genetic epilepsies and 74% (39/53) of metabolic epilepsies.
Conclusions: Genetic and metabolic epilepsies present with a highly heterogeneous clinical picture with early onset of seizures and a broad spectrum of genetic diagnoses. Although these disorders are classified under the genetic and metabolic etiologies of epilepsy, each disorder is a distinct entity with a unique clinical course and characteristic comorbidities. The abundance of autosomal recessive inheritance patterns of inherited metabolic disorders could explain the metabolic group's higher consanguinity rate. Abnormal imaging findings should not rule out genetic causes in childhood epilepsy. Molecular genetic tests should be utilized early when genetic and metabolic etiologies are suspected.
Funding: We declare no external funding for this study.
Genetics