Epilepsy and genetics
Epilepsy, also known as seizure disorder, is a chronic neurological condition characterized by abnormal bursts of electrical activity in the brain, leading to seizures that can affect consciousness and sensory perception. This disorder affects millions globally and can impact individuals across all age groups. The etiology of epilepsy is complex and can be idiopathic (unknown cause) or symptomatic (with identifiable causes), such as head injuries, infections, or tumors. Genetic factors play a significant role, as some forms of epilepsy have been linked to hereditary patterns.
Research indicates that children of parents with epilepsy have an increased risk of developing the condition, particularly in cases of generalized seizures, which are more likely to have a genetic basis. Numerous genetic syndromes, including Dravet syndrome and juvenile myoclonic epilepsy, have been associated with specific genetic mutations. While genetic testing can confirm some monogenetic forms of epilepsy, many syndromes present complex inheritance patterns that may not benefit from such tests. Treatment options primarily include antiepileptic drugs, with varying effectiveness, and alternatives like vagus nerve stimulation or surgery for intractable cases. Ongoing research into molecular genetics and new therapeutic approaches continues to evolve, offering hope for improved management of epilepsy.
Epilepsy and genetics
ALSO KNOWN AS: Seizure disorder
DEFINITION Epilepsy is a chronic brain disorder of the cerebrum whereby the brain produces sudden bursts of electrical energy abnormally interfering with consciousness and all types of sensations. It disrupts the nervous system, which can cause mental and physical disorders. Epilepsy with a known cause is called either secondary or symptomatic epilepsy. The most common type is the idiopathic or unknown type, which accounts for six out of ten cases.
Risk Factors
Primary factors are head injuries, infections in the central nervous system, and tumors. Another factor is cerebrovascular disease, a condition characterized by its effects on the brain and its blood supply. A family history seems to influence the tendency toward epilepsy. According to the Centers for Disease Control and Prevention (CDC) in 2022, epilepsy actively affects more than three million Americans; the World Health Organization (WHO) estimated in 2022 that around fifty million people worldwide had epilepsy. It affects all age groups.
Etiology and Genetics
Symptomatic idiopathic (unknown) epilepsy has been discovered to start between the ages of two and fourteen. Seizures before the age of two usually indicate developmental defects.
Epilepsy is divided into two categories, partial and generalized, because of specific biological mechanisms at work. Partial, also called focal or localized, seizures occur more often than do generalized seizures. They can occur in one or more locations in the brain. Partial seizures can spread more widely in the brain, depending on the severity of the seizure.
Epilepsy is not a single disorder: It contains multiple gene factors that are influenced by the environment. Some types of epilepsy run in families, and children of parents who have epilepsy have a risk range from 4 to 8 percent, some studies show. People with generalized seizures, in which both sides of the brain are involved, tend to have other family members affected by epilepsy more often than those with localized seizures.
Generalized seizures are more likely to be genetically based. Some types of epilepsy can be inherited. Epilepsies such as West syndrome or infantile spasms can cause delays in development of children between four and eight months of age. Juvenile myoclonic epilepsy has another name, impulsive petit mal epilepsy, which is characterized as general seizures with spasmodic movements called myoclonic jerks.
Several epilepsy syndromes start in the baby’s first year of life. Studies in molecular genetics have identified problematic genes for some of them. A condition known as hypoxic-ischemic encephalopathy is the major cause of epilepsy in the first year of life. Other etiologies during infancy are chromosomal disorders and brain disorders.
Sometimes there is an absence of seizures in individuals between ages eight to twenty. Adult myoclonic epilepsy is a distinct syndrome that involves the development of generalized epilepsy at a later age.
Lennox-Gastaut syndrome is a very serious form of epilepsy in children, which causes multiple seizures and developmental disability. There are partial seizures and an absence of muscle control. A person with this condition has difficulty standing and sitting.
Progressive myoclonic epilepsy is an inherited disorder that affects children from the age of six to fifteen but can also occur as an adult. It is characterized by light sensitivity, and the seizures are tonic-clonic. Early studies suggested that the disorder would continue to worsen throughout their life, but better treatment has improved this outlook.
Autosomal dominant nocturnal frontal lobe epilepsy is an inherited syndrome that is rare, and typically occurs during childhood. The onset varies among families, with twisting contractions or thrashing. These seizures are dystonic and occur at night for a short period of time. Landau-Kleffner syndrome is an epileptic condition that leads a person to have difficulty in writing and speaking (aphasia). Benign familial neonatal convulsions (BFNC) are very rare. This form of generalized seizure has a hereditary factor to it.
Status epilepticus (SE) is a potentially life-threatening condition which can lead to chronic epilepsy. It can cause death or permanent brain damage if not treated correctly and quickly. This condition is associated with any seizure that lasts for more than five minutes, or when multiple seizures occur within five minutes and are interrupted only briefly for partial relief. Generalized or tonic-clonic type is the most serious form of SE. The trigger is unknown.
Dozens of genetic syndromes covering a variety of seizure patterns may cause different types of epilepsy. Some genetic causes have been identified for a few cases of juvenile myoclonic epilepsy, which most sources say is present in about 5 to 10 percent of all persons with epilepsy. Some research has suggested that the GABA signaling system is an important element in many cases of epilepsy.
Some epilepsy syndromes have a genetic inclination, which has created the possibility of genetic testing. Genetic testing has drawbacks, however, as only monogenetic (single-gene) epilepsies can be confirmed. Dravet syndrome (severe myoclonic epilepsy in infancy) and benign familial neonatal seizures (BFNS) are easy to recognize, and early genetic testing may benefit these syndromes. Other epileptic syndromes have complex patterns that would not be aided by genetic testing.
Symptoms
The hallmark of epilepsy is seizures. Some temporary symptoms can be loss of awareness and movement, which includes vision, hearing, taste, mood, and mental function. Seizure problems often create physical problems (such as bruising easily or breaking bones) as well as psychosocial or mental problems.
Screening and Diagnosis
A diagnosis of epilepsy comes in multiple steps. A blood workup and neurological exams are needed. A complete medical history is important, and a family history to gather as much information as possible. The health care provider should find out when the seizure began and what it looked like. The next step is to identify the type of seizure and whether it falls under a recognizable syndrome. A clinical evaluation is important to determine the source of the epilepsy.
Doctors will use an electroencephalograph (EEG), which measures brain waves, to determine any abnormal patterns in the brain. A computed tomography (CT) scan uses more sensitive imaging equipment than a single X-ray. It provides clear images of organs such as the brain and heart and is another tool to help identify seizure activity.
Treatment and Therapy
Antiepilepsy drugs (AEDs) that suppress seizures are the main treatment regimen for epilepsy. These include lamotrigine, gabapentin, and topiramate. About 30 percent of patients do not find these medications effective. Moreover, the drugs often cause side effects such as weight gain or loss, blurry vision, dizziness, and other problems and may cause problems with the liver or other organs, so blood tests and other forms of monitoring are common. The WHO reports that about 75 percent of people with epilepsy in low-income countries do not receive treatment. Stimulation of the vagus nerve (a large nerve in the back of the neck) was approved late in the twentieth century for adults and children; this procedure is still being used in the twenty-first century when medications to control seizures fail. It is designed to send light electrical pulses regularly to the back of the brain via the vagus nerve to prevent further seizures. One of the complications with vagus nerve stimulation is that it does not eliminate seizures in all patients. In fact, it can cause shortness of breath, sore throat, vomiting, nausea, and ear and throat problems. Epilepsy surgery is used when the area of the brain in which the seizures originally started can be isolated or removed. About 20 percent of patients have intractable seizures, or those that do not respond to any treatment.
In 2024, it was announced that researchers at the Francis Crick Institute had identified a new potential treatment for a common form of genetic epilepsy called CDKL5 deficiency disorder, or CDD. This deficiency and the disorder are caused by a lack of CDKL, an enzyme that alters the function of certain proteins. Researchers expressed optimism that this discovery could lead to a way to restore the enzyme and reduce or eliminate the resulting epilepsy.
Prevention and Outcomes
For the most part, what causes epilepsy is still unknown. Idiopathic epilepsy cannot be prevented. However, it is known that head injuries, a common cause of epilepsy, can often be prevented, such as by wearing a helmet when riding a bicycle, motorcycle, or horse or taking part in any activity for which head protection would be beneficial. Scientists from all over the world constantly seek out the best antiepilepsy drugs and study the way in which neurotransmitters react to brain cells to control nerve firing. Scientists are continuing to improve MRI and other diagnostic tools. Some studies suggest that children can have fewer seizures if they maintain a ketogenic diet, which consists of a high intake of fats and a low one of carbohydrates. Scientists are also working with stem cells to further improve the treatment of epilepsy.
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