Narcolepsy and genetics
Narcolepsy is a neurological disorder that disrupts the sleep-wake cycle, leading to involuntary daytime sleep attacks, which can occur at inopportune moments. Genetic factors play a significant role in narcolepsy, particularly among individuals with close relatives affected by the condition, as they have a higher risk compared to the general population. While the inheritance pattern is not clearly defined, some researchers propose an autosomal dominant pattern with incomplete penetrance, suggesting that a single mutant gene may increase susceptibility without guaranteeing the disorder's development.
A strong association exists between narcolepsy, particularly type 1, and the human leukocyte antigen (HLA) allele DQB1*06:02, thought to be involved in an autoimmune response that damages brain cells responsible for wakefulness. Additionally, other genetic mutations, such as those in TNF and T-cell receptor alpha (TCRA), may contribute to susceptibility, though they are not definitive causes. Symptoms typically arise in adolescence and can include excessive daytime sleepiness, cataplexy, temporary sleep paralysis, and hallucinations. Diagnosis often involves clinical evaluation and specific sleep tests. While treatment options include medications and lifestyle adjustments to manage symptoms, there are currently no established guidelines for preventing narcolepsy itself.
Narcolepsy and genetics
DEFINITION Narcolepsy is a disorder of the nervous system that affects the sleep-wake cycle. It results in frequent, involuntary episodes of sleep during the day. Sleep attacks can occur while patients drive, talk, or work.
Risk Factors
Individuals who have first-degree relatives—such as parents, siblings, and children—with narcolepsy are at a much greater risk of developing the disorder than the general population; however, narcolepsy does not have a clear pattern of inheritance. Most cases of narcolepsy are sporadic and can occur in individuals with no family history of the disorder.
Etiology and Genetics
Most cases of narcolepsy probably result from a combination of genetic and environmental factors. Individuals who have close relatives with narcolepsy have an approximately 1 to 2 percent probability of developing the disorder, a rate that is roughly ten to forty times higher than the general population. Some researchers have suggested an autosomal dominant pattern of inheritance with incomplete penetrance in these familial cases. This means that a single copy of the mutant gene is sufficient to predispose the disease, but not all people with the mutant gene will develop narcolepsy. Twin studies also suggest a significant environmental component. In only 25 percent of cases where one identical twin has narcolepsy does the other twin develop the condition.
Molecular genetic evidence suggests that narcolepsy is strongly associated with the human leukocyte antigen (HLA) allele DQB1*06:02, which can be found as part of the major histocompatability locus found on chromosome 6. The majority of people who have narcolepsy with cataplexy have the HLA gene variant DQB1*0602. There is speculation that HLA variants can predispose some people to an autoimmune reaction that destroys cells in the brain that produce hypocretins (small proteins known to induce wakefulness). Mutations in two other genes, TNF and the T-cell receptor alpha (TCRA), have been reported to cause susceptibility to narcolepsy. However, not all people with narcolepsy have these variant genes, and many people who do have these variant genes never experience symptoms of narcolepsy.
Experts have identified two types of narcolepsy: narcolepsy type 1 and narcolepsy type 2. Those with type 1 have a variation of the HLA gene. They have found a strong genetic link in those with type 1 narcolepsy. Type 2 narcolepsy, on the other hand, may have some genetic variants. However, researchers do not yet have a solid understanding of this type of narcolepsy, which is rare.
Symptoms
Symptoms of narcolepsy usually start during adolescence. The onset of the disorder may occur in individuals from five to fifty years old. Symptoms include excessive daytime sleepiness, involuntary sleep attacks, unrefreshing sleep, a sudden loss of muscle tone without loss of consciousness (cataplexy), temporary sleep paralysis while awakening, and hallucinations as one falls asleep or wakes. Symptoms may be triggered by a monotonous environment, a warm environment, eating a large meal, and strong emotions.
Screening and Diagnosis
The doctor will ask about a patient’s symptoms and medical history, and a physical exam will be done. If narcolepsy is suspected, a patient may be referred to a specialist in sleep disorders.
Tests may include a multiple sleep latency test (MSLT) to measure the onset of rapid eye movement (REM) sleep, which occurs earlier than normal in narcolepsy. A general sleep lab study is often performed the night before an MSLT. This test helps to rule out other causes of daytime sleepiness by monitoring brain waves, eye movements, muscle activity, respiration, heartbeat, blood oxygen levels, total nighttime sleep, the amount of nighttime REM sleep, the time of onset of REM sleep, and the degree of daytime sleepiness.
Treatment and Therapy
Treatment may include stimulant medications that increase levels of daytime alertness. Antidepressants such as selective serotonin reuptake inhibitors (SSRIs) can help treat many symptoms of narcolepsy, including cataplexy, hallucinations, and sleep paralysis. Sodium oxybate has been found to be effective in the treatment of cataplexy.
Other treatment options include taking planned short naps throughout the day and wearing a medical alert bracelet or pendant.
Prevention and Outcomes
There are no guidelines for preventing narcolepsy itself. However, patients can try to prevent symptoms by avoiding activities that carry a risk of injury from a sudden sleep attack, such as driving, climbing ladders, and using dangerous machinery. Other preventive measures include exercising on a regular basis, avoiding nicotine and alcohol, and maintaining a consistent sleep schedule.
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