• Most cases of narcolepsy are sporadic, occurring at random in the general population.
• There is a small, but increased chance of developing narcolepsy if a family member has it too.
• Certain genes have been associated with narcolepsy.
• Many people have these genes and do not develop narcolepsy; there is also an environmental trigger involved.

According to the National Institute of Neurological Disorders and Stroke, 135,000 to 200,000 people in the United States are believed to have narcolepsy. It usually begins in adolescence and can continue for a person’s whole life. The exact cause of narcolepsy in most cases is unknown. While it’s not fully understood what causes narcolepsy and why some people get the condition and some don’t, there can be a familial component. If you have a family member with narcolepsy, you are 20 to 40 times more likely to later develop narcolepsy than someone in the general population.

This statistic may frighten people with narcolepsy, as it seems like a grim indicator that either your children will inherit it or another family member will later develop the sleep condition. But because narcolepsy is brought on by a unique combination of genetic and environmental factors, the actual risk of inheritance is low. Here’s the breakdown of the development of narcolepsy, whether narcolepsy is inherited, and whether it can be passed down to others.

Types of Narcolepsy

Narcolepsy is usually divided into two categories, type 1 and type 2. Low levels of hypocretin (also called orexin) are the main cause of type 1 narcolepsy. Hypocretin is responsible for regulating the sleep cycle, including rapid eye movement or REM sleep — when dreams occur — and the deeper, non-REM sleep that helps you wake up refreshed. Type 1 narcolepsy is diagnosed when a person has low levels of hypocretin, as well as the sleep disturbances and daytime drowsiness most people think of as being part of narcolepsy (excessive daytime sleepiness, sleep paralysis, sudden sleep attacks). Cataplexy — sudden attacks of muscle weakness while awake — is also part of the diagnosis of type 1 narcolepsy. Type 2 narcolepsy has the sleep disturbances of type 1, but not the low hypocretin levels or the cataplexy.

Nearly all studies on the genetic inheritance of narcolepsy involve type 1. Specific markers for type 2 have not been found yet. The rest of this article will discuss type 1 narcolepsy.

The Basis of Inheritance

Inherited conditions are usually thought of as genetic, but the process of inheritance is not clear to most people. You may remember Punnett squares from biology class and assume all conditions are inherited based on a dominant or recessive gene pattern. In reality, inherited conditions happen in a variety of ways. They can be caused by mutations in a single gene, when a gene from one parent or another mutates before conception (in either the sperm or egg) or after conception and the trait appears in the child. Other inherited conditions have a basis in genes, but are dependent on environmental experiences before or after birth that cause the genes to express themselves.

The simplest way to see how a trait is inherited is to conduct a survey of monozygotic (identical) twins and compare them to dizygotic (fraternal) twins. Identical twins share a genetic code, while fraternal twins are no more alike genetically than any other set of siblings. So if a condition is as common in identical twins as fraternal ones, it indicates that the environment — more than genetics — plays a factor in its development.

How Is Narcolepsy Inherited?

There is no clear pattern for the inheritance of narcolepsy. Available research suggests narcolepsy may have a genetic basis, but also requires certain environmental conditions to develop in a person. One twin study found that just 20 percent to 30 percent of identical twins, who have the same genes, shared a diagnosis of narcolepsy.

Specific genetic markers have been found to correlate with a risk of narcolepsy. The most studied of these is the HLA-DQB1 gene, located on chromosome 6 and part of a genetic family called the human leukocyte antigen (HLA) complex. While there are many variations in this gene, the particular variant HLA-DQB1*06:02 is associated with narcolepsy and is also important for immune function. Researchers currently suspect narcolepsy is an autoimmune disorder in which the immune system attacks the neurons that produce hypocretin, the substance that regulates sleep patterns.

A variant in T-cell receptor genes has also been associated with narcolepsy. For people with narcolepsy, these T-cell receptors are believed to combine with HLA in the nervous system and destroy cells in the brain that produce hypocretin.

Will I Pass on Narcolepsy?

It’s important to remember these genetic markers are only associated with narcolepsy. Having one does not mean a person will develop narcolepsy, and people who do not have any of these genetic variants can still develop narcolepsy. Most cases of narcolepsy are sporadic, meaning they occur without a definitive inherited pattern.

A quarter of the world’s population has the HLA-DQB1*06:02 gene variant, and narcolepsy only occurs in 1 in 2,000 people. So even if a person with narcolepsy passes on the HLA-DQB1*06:02 gene variant, it is unlikely their child would have the sleep disorder. There is only a 1 percent chance that a parent with narcolepsy will have a child with narcolepsy.

Environmental and Genetic Causes of Narcolepsy

One study found that while virtually all people with type 1 narcolepsy had the HLA-DQB1*06:02 gene variant, this was not the only factor in developing the condition. There seems to be a need for a specific environmental trigger that affects the immune system to make the gene variant express narcolepsy.

All of the genes associated with narcolepsy to date are also associated with the immune system. Research has shown that shortly after the first symptom of narcolepsy develops, a person also tends to have high levels of antibodies towards the bacteria streptococcus. Also, many cases of narcolepsy begin in the early summer and late spring, suggesting a winter viral or bacterial infection could be a trigger. These immune system assaults seem to inspire an autoimmune attack on hypocretin-producing neurons, even before the symptoms of narcolepsy are visible.

The statistic that someone with a family member with narcolepsy is 20 to 40 times more likely to develop narcolepsy as well sounds ominous. However, in reality, the chance of inheritance is quite low. Current research suggests that only 1 percent to 2 percent of those with narcolepsy have a first-degree family member with the condition.

While it is possible to pass on genetic markers that make a person more predisposed to developing narcolepsy, researchers believe that both a genetic and an environmental component are required for the condition to develop. The vast majority of narcolepsy cases occur randomly and do not have a familial basis.

Do you have a family member with narcolepsy? Do you have questions about the inheritance of narcolepsy? Comment below or start a conversation on MyNarcolepsyTeam.