A quest to find the genes responsible for childhood epilepsies

Epilepsy is the most common serious neurological illness of children and young people. An estimated 38,000 New Zealanders live with this condition, with 80 per cent having their onset in childhood. Although these individuals may live relatively normal lives, one third have seizures with major social, psychological, physical and cognitive consequences. 

Many of these seizures cannot be controlled by antiepileptic medication. Severe epilepsies starting in childhood have a mortality rate of 25% by 20 years of age; and most of these have a direct genetic cause.

Over 450 children develop epilepsy each year. Constant seizures can lead to profound physical, psychological and social consequences for kids; also increasing anxiety and socially avoidant behaviour. Coupled with this, children often receive inadequate schooling, and later in life are overrepresented in unemployment statistics, adding to the reduction in quality of life. 

Overcoming knowledge gaps in epilepsy research is fundamental to reducing adverse effects associated with epilepsy and giving these kids the quality of life they deserve.

Professor Lynette Sadleir is a paediatric neurologist specialising in epilepsy at the University of Otago Wellington campus. Her work, and that of her supporting team, focuses on studying families where several individuals have epilepsy or where a certain child has an especially severe form.

New Zealand families, ascertained through established New Zealand referral networks, will be studied. Each family member will be interviewed using a validated seizure questionnaire. Eyewitness accounts of seizures will be sought and an extensive family pedigree constructed. 

Previous medical records and investigations will be obtained including EEG, MRI and neuropsychological assessments. Each individual’s epilepsy will be characterised. Inspection and analysis of the family history will be performed to determine the mode of inheritance of the epilepsy. DNA will be extracted from blood or saliva. Molecular genetic studies including whole exome and whole genome sequencing will be performed to identify novel causative genes.

Dr Sadleir’s work was last year expanded into studying Auckland-based families, which, with such a large population, is a great source of data. She and her team have already had successes in discovering genes in the Auckland arm.

With the increasing importance of learning about the genome, this work will become more and more critical for informing targeted treatments which will improve the quality of life of those living with epilepsy and hopefully save the lives of the several children who die each year as a result of their epilepsy.