Genetic aetiologies and phenotypic variations of childhood-onset epileptic encephalopathies and movement disorders

Thesis event information

Date and time of the thesis defence

Topic of the dissertation

Genetic aetiologies and phenotypic variations of childhood-onset epileptic encephalopathies and movement disorders

Doctoral candidate

Licentiate of Medicine Jonna Komulainen-Ebrahim

Faculty and unit

University of Oulu Graduate School, Faculty of Medicine, PEDEGO

Subject of study

Paediatric neurology


Adjunct Professor Tarja Linnankivi, HYKS


Professor Johanna Uusimaa, University of Oulu

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Whole-exome-sequencing is a useful tool in diagnostics of childhood-onset epileptic encephalopathies and movement disorders

Epilepsy is one of the most common neurological conditions. Approximately half percent of children have epilepsy. In epileptic encephalopathy, the epileptic activity itself may contribute to severe cognitive and behavioral impairments above and beyond to what might be expected from the underlying pathology alone. Movement disorders comprise a heterogenous group of disorders that lead to impairment of voluntary movement, abnormal postures, or inserted involuntary movements.

It is estimated that more than half of the epilepsy cases have a genetic basis for their condition. Next-generation sequencing (NGS) methods have increased the knowledge on genes causing childhood-onset epileptic encephalopathy and movement disorder. The symptoms, phenotype, caused by the same gene can vary significantly and the same phenotype can be caused by many different genes. Drug-resistant epilepsy due to inborn error of metabolism should be diagnosed early in order to prevent permanent neurological damage.

The aim of this study was to discover novel genetic causes and phenotypes of childhood-onset drug-resistant epilepsy, epileptic encephalopathies and movement disorders. Furthermore, the use of whole-exome sequencing, NGS method, as a diagnostic tool in clinical practice was evaluated.

Altogether, 12 children who had been followed-up in the Oulu University Hospital due to drug-resistant epilepsy and/or movement disorder with undefined aetiology, were included in the study. Novel phenotypes and gene variants were found related to epileptic encephalopathies and movement disorders in GABRG2, NACC1, SAMD9L and MTR genes. Patients with pathogenic SAMD9L and MTR variants had both neurologic and haematologic symptoms.

Since publishing the results, pathogenic SAMD9L gene variants have been identified as one the most common genetic findings in inherited bone marrow failure. Whole-exome sequencing for 10 patients with drug-resistant epilepsy or epileptic encephalopathy provided a genetic diagnosis for two patients (20%). Even the next-generation sequencing methods have made the diagnostics of epileptic encephalopathies and movement disorders easier, the majority remain unsolved. New phenotypes are found caused by variants in known genes. Exome-sequencing and gene panels have become part of diagnostics of early-onset neurological diseases with wide genotypic-phenotypic variation and possibly requiring targeted treatment. NGS methods also findings with uncertain significance and risk factors for other diseases. Therefore physicians using NGS methods should know the benefits and limitations of these methods and have active collaboration with clinical geneticists.
Last updated: 1.3.2023