Epileptic Encephalopathies of Childhood: The New Paradigm of Genetic Diagnosis

Rita Martins, Oana Moldovan, Ana Berta Sousa, António Levy, Sofia Quintas


Introduction: Epileptic encephalopathies of childhood are characterized by early seizure-onset and adverse neurological outcomes. The development of new genetic techniques has allowed an exponential identification of the genes that are involved. Over the last years, we have observed a revolution in the diagnostic paradigm. However, there are no international guidelines regarding the diagnosis of genetic epileptic encephalopathies. We aim to discuss the current knowledge about the genetic architecture of epileptic encephalopathies of childhood.
Material and Methods: review of the literature about infantile epileptic encephalopathies and the genetic tests currently available. A systematic approach and a diagnostic algorithm to use in clinical practice were proposed.
Results: Initially the patient’s phenotype should be determined based on the seizure type, electroencephalogram pattern and neuroimaging. Patients with unclear etiology after brain magnetic resonance imaging should undergo an appropriate metabolic investigation to promptly exclude treatable conditions. Further studies should also include other genetic causes, mainly if associated with particular phenotypic features. Chromosomal microarray analysis should be firstly considered, particularly if dysmorphic or polymalformative abnormalities are present. If this is negative and/or there are no physical features, the next step should be next-generation sequencing multigene panels or whole-exome sequencing. Single gene study should only be considered when the patient’s phenotype is highly suggestive of a specific syndrome.
Conclusion: The revolution of the genetic knowledge about epileptic encephalopathies of childhood has led to a complex diagnostic approach. This new paradigm poses significant implications in genetic counselling, treatment and prognosis.


Brain Diseases/complications; Child; Epilepsy/diagnosis; Genetic Testing

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