Epilepsy comprehensive panel

The clinical presentation of epilepsy is highly variable and depends on the region of the brain involved and the underlying cause. Seizures may begin in a single area of the brain (focal seizures), involve both hemispheres from onset (generalised seizures), or include both focal and generalised seizure types. Symptoms may include brief episodes of impaired awareness, involuntary movements, sensory disturbances, behavioural arrest, muscle stiffening, rhythmic jerking, sudden loss of muscle tone or convulsive events. Some epilepsy syndromes are associated with additional neurological features such as developmental delay, intellectual disability, autism spectrum disorder, movement disorders or cognitive regression.

Many epilepsy syndromes have characteristic ages of onset, EEG findings, neuroimaging features and natural histories, allowing clinicians to establish a syndrome diagnosis that guides management and prognosis.

The recommends a structured approach to diagnosis, classifying patients according to seizure type, epilepsy type and, where possible, a specific epilepsy syndrome. In parallel, identifying the underlying cause is an essential part of the diagnostic process, as it may influence treatment selection, prognosis, recurrence risk and eligibility for precision therapies.

Epilepsy is one of the most common serious neurological disorders, affecting approximately 0.5–1% of the global population. The lifetime risk of developing epilepsy is estimated to be approximately 3%.

The incidence is highest during the first year of life and after 60 years of age. While epilepsy can occur at any age, many genetic epilepsies and developmental and epileptic encephalopathies present during infancy or childhood.

Pathogenic variants have been identified in hundreds of genes involved in neuronal development, synaptic transmission, ion channel function, neurotransmitter signalling and brain metabolism.

Some genetic epilepsies occur as isolated disorders, whereas others form part of broader neurodevelopmental syndromes. Common genes associated with epilepsy include SCN1A, SCN2A, SCN8A, KCNQ2, STXBP1, PCDH19, DEPDC5, PRRT2, KCNT1, SLC2A1, and many others.

The genetic conditions associated with epilepsy follow heterogeneous inheritance patterns. Across the spectrum, autosomal dominant, autosomal recessive, X-linked, and mitochondrial inheritance are all represented; de novo variants account for a notable share of cases within the developmental and epileptic encephalopathies.

• Where epilepsy is suspected to have a genetic cause, molecular genetic testing can identify the underlying condition and confirm a clinical suspicion.
• The identified entity guides further clinical management and is a prerequisite for targeted medical care; therapeutic options are evaluated individually by the treating physicians.
• Identification of the underlying pathogenic germline variant enables predictive testing of at-risk family members and provides information relevant to family planning.

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