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Genetic and clinical variations of developmental epileptic encephalopathies
Gül Demet Kaya Özçora1, Elif Söbü2, Uğur Gümüş3
1Faculty of Medical Sciences Pediatric Neurology Dept, Gaziantep Hasan Kalyoncu University, Gaziantep, Turkey.
Insights
Developmental and Epileptic Encephalopathy (DEE) involves severe early-onset epilepsy with neurodevelopmental issues. Genetic analysis is crucial for diagnosis, as genotype-phenotype correlations are absent in DEE patients.
Area of Science:
- Genetics
- Neurology
- Developmental Pediatrics
Background:
- Developmental and Epileptic Encephalopathy (DEE) encompasses severe early-onset epilepsy where neurodevelopmental comorbidities arise from underlying causes and uncontrolled seizures.
- A direct genotype-phenotype correlation is not established for DEEs, necessitating comprehensive genetic and clinical evaluations.
Purpose of the Study:
- To investigate the genetic and phenotypic variations among patients diagnosed with DEE.
- To highlight the diagnostic utility of genetic analysis in complex neurodevelopmental disorders.
Main Methods:
- Genetic evaluations were performed on 20 children (aged 0-16 years) with DEE, considering epilepsy, developmental delay, motor deficits, autistic features, or cognitive impairment.
- Patients underwent assessment of demographics, medical/family history, psychomotor development, seizure control, EEG, and MRI.
Main Results:
- Specific DEE types (2, 4, 6B, 7, 11, 26, 30, 33, 35, 42, 58, 62, 67) were identified. Status epilepticus occurred only in DEE7.
- Multifocal epileptic discharges (35%) and burst-suppression patterns were common EEG findings. 80% had normal MRI scans. Refractory epilepsy was present in 33% of cases.
- De-novo mutations, microcephaly, and dysmorphic features correlated with resistant seizures and poor prognosis.
Conclusions:
- Genetic analysis, particularly next-generation sequencing, is the primary diagnostic tool for DEE and related neurodevelopmental disorders.
- Understanding genetic and phenotypic differences is vital for managing DEE, despite the lack of clear genotype-phenotype correlations.
Objective:
The concept of 'developmental and epileptic encephalopathy (DEE)' recognises that in infants presenting with severe early-onset epilepsy, neurodevelopmental comorbidity may be attributable to both the underlying cause and to adverse effects of uncontrolled epileptic activity. There is no direct genotype - phenotype correlation in DEEs. This study aimed to report the genetic and phenotypic differences in patients with DEE.
Methods:
Genetic evaluations of the patients were performed due to epilepsy combined with developmental delay, epileptic encephalopathy, motor deficits, autistic features, or cognitive impairment. Patients were assessed for demographic characteristics, medical history, family history, psychomotor development, seizure control interventions, electroencephalogram (EEG) and magnetic resonance imaging (MRI) findings.
Results:
This study included 20 children aged 0-16 years who were diagnosed as having DEE.The types of DEE detected in our study were DEE 2, 4, 6B, 7, 11, 26, 30, 33, 35, 42, 58, 62, and 67.Status epilepticus was recorded in only DEE7. The most common EEG abnormality was multifocal epileptic discharges (35%,) followed by burst-suppression patterns in patients with neonatal-onset seizures. Thirteen of the children were aged over 2 years, two (15%) were non-ambulatory and six (46%) were non-verbal. MRI scans were normal in 80% of the patients. Refractory epilepsy seen in 33% of cases.De-novo mutation, microcephaly and dysmorphic findings accompany resistant seizures and are associated with poor prognosis.
Discussion:
For patients with movement disorders, developmental delay, autism, and ID with or without epilepsy in any period of their life, next-generation sequencing is the only diagnostic technique available, with genetic analysis often being the only diagnostic method.
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