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A comparison of genomic diagnostics in adults and children with epilepsy and comorbid intellectual disability

A comparison of genomic diagnostics in adults and children with epilepsy and comorbid intellectual disability

Dr. Katie Benson writes about her latest paper, which has just been published in the European Journal of Human Genetics.

FutureNeuro clinicians and geneticists joined forces with industry collaborators Congenica to compare genomic diagnostic rates in the adult and paediatric epilepsy clinic. The work was published in the European Journal of Human Genetics. Epilepsy is a common neurological disorder affecting 50-60 million people worldwide. A considerable portion of these patients are thought to have an underlying genetic cause or predisposition driving their epilepsy. In some of these cases, a change or mutation in a single gene can be identified which is the specific underlying cause of the person’s epilepsy. Such genetic changes can now be detected using genetic sequencing technology.

This article describes the utility of these genomic diagnostics in the form of array-comparative genomic hybridisation (array-CGH) and whole exome sequencing (WES) in adult and paediatric epilepsy patients with intellectual disability. While these genetic tests are widely used in the paediatric clinic, the diagnostic yield in adult epilepsy patients is less well understood. This study was conducted to inform the clinical utility of genomic testing in adult epilepsy patients compared with a similar cohort of children.

A cohort of 101 adult and paediatric patients underwent genomic testing and a genetic diagnosis was made in 33 cases overall (33%). In the paediatric group 41% of patients received a genetic diagnosis while in the adult group 30% of patients received a genetic diagnosis. Three patients were also referred for follow-up clinical testing as a result of incidental genetic findings unrelated to their epilepsy detected during genetic testing.

The authors have demonstrated that genetic diagnostics are important in the adult epilepsy setting. These adult patients may not have had a previous genetic diagnosis due to an absence of genetic knowledge when they were children themselves, and also due to an under-appreciation and poor availability of appropriate genetic testing as these individuals grew into adulthood. While it is clear that interventions in childhood may improve prognosis and outcomes, interventions in adulthood may also positively affect seizure control and have a considerable impact on quality of life.

By identifying a genetic diagnosis, it may be possible to adapt a patient’s treatment to improve their seizure control. Of 33 patients who received a genetic diagnosis in this study, four had potential to change their treatment on the basis of their new diagnosis. For the three patients with mutations in SCN1A, sodium channel blockers will be avoided, as these class of anti-epileptic drugs may exacerbate seizures in this setting. Another patient with a variant in TSC1 may be eligible for treatment with the drug everolimus. Other patients who received a genetic diagnosis may now be able to engage with a specific gene-related support group and in the future may be considered for treatment with new emerging gene-specific therapies. A genetic diagnosis can be hugely important to the families of people with severe epilepsy syndromes for family planning and may remove any perceived sense of blame within families.

This study has illustrated that genetic testing in the form of WES and array-CGH has immense value for diagnostics and prognostics in both adult and paediatric patients. It is important that as diagnostic testing becomes embedded into the clinical care pathway for patients with complex epilepsy, health care professionals are educated in these new technologies. It is also imperative that state and private funders are made aware of the clinical and cost benefits of the integration of appropriate diagnostic genetic testing into clinical practice.