Sleep apnea: is this common sleep disorder hereditary?

There are many reasons you could feel tired during the day, but a common one is poor quality sleep caused by sleep apnea. This sleep disorder in which breathing repeatedly stops and restarts throughout sleep, affects around 1 billion adults worldwide, although there may be many more undiagnosed cases [1]. Children can also suffer from sleep apnea, although the prevalence is much lower at 2% [2].

While the main symptoms of snoring and excessive tiredness are unpleasant, the consequences of untreated sleep apnea can be serious. A logical question then, is what causes so many people to have this sleep disorder? A clear answer is difficult, as many factors are known to increase someone’s risk of developing sleep apnea; however, genetics and preexisting conditions play a large causal role. In this article, we take an in-depth look at sleep apnea and discuss not only symptoms, risk factors and genetic causes, but also diagnosis and treatment options.

What is sleep apnea?

Sleep apnea is a condition where breathing stops and starts repeatedly during sleep. This occurs many times per hour during sleep, reducing the quality of sleep and lowering blood oxygen levels. The result is a variety of symptoms, including extreme tiredness during the day.

Types of sleep apnea

There are three main types of sleep apnea [3]:

• Obstructive sleep apnea (OSA)
• Central sleep apnea (CSA)
• Treatment-emergent central sleep apnea

Although the symptoms are essentially the same for all types, the causes differ.

Obstructive sleep apnea

Obstructive sleep apnea (OSA) is the most common form of sleep apnea. It occurs when muscles in the neck and back of the throat relax causing the soft tissue to collapse and press on the windpipe when you breathe in. This temporarily reduces (hypopnea) or even stops (apnea) airflow in the upper airway for at least 10 seconds. When your brain realizes that you cannot breathe, you wake up, often with a gasp as the airway opens, allowing you to breathe normally [3, 4]. When you fall back to sleep the process repeats itself. The frequency of hypopneas and apneas varies between individuals, but typically ranges from 5-30 per hour; it is used to categorize the severity of OSA [3, 5].

Central sleep apnea

Central sleep apnea (CSA) is caused by problems with the signals sent by the brain to the muscles that control breathing [3, 4].

Treatment-emergent central sleep apnea/complex sleep apnea

Treatment-emergent central sleep apnea, or complex sleep apnea, occurs in people receiving treatment for OSA [3, 4].

Symptoms of sleep apnea

Common symptoms of OSA and central sleep apnea that occur during sleep include

• Snoring: although this is the main symptom of sleep apnea, it is sometimes absent and not everyone who snores has sleep apnea
• Episodes where breathing stops and starts: usually noticed by someone else
• Gasping for air during sleep, or making snorting or choking noises
• Waking up gasping for air
• Waking up a lot in the night (insomnia): may be associated with a need to urinate
• Night sweats
• Feeling restless at night
• A dry mouth when you wake up
• Feeling exhausted when you wake up
• Headache when you wake up

Common daytime symptoms include

• Extreme daytime tiredness or sleepiness (hypersomnia)
• Poor concentration and memory loss
• Irritability, depression and anxiety

Additionally, a characteristic breathing pattern of fast, deep then shallow breaths followed by a pause, called Cheyne-Stokes breathing, occurs with central sleep apnea, especially where there is an underlying heart condition [6, 7].

Children with sleep apnea may also wet the bed, move around a lot in their sleep and sleep in strange positions. During the day, they may be hyperactive and under-perform in school [4].

Causes of sleep apnea

There are many factors known to increase your risk of having OSA, including [3, 8, 9]

• Obesity: known to greatly increase risk
• Age and gender: men are more likely to develop OSA than pre-menopausal women, and the risk increases for both sexes with age
• Alcohol consumption
• Family history
• Having a large neck
• Having large tonsils, a narrowed airway or nasal congestion
• Lung diseases, such as chronic obstructive pulmonary disease (COPD) and asthma
• Medical conditions, such as cleft lip/palate, Down syndrome, high blood pressure, type 2 diabetes, heart failure, hormone disorders, and polycystic ovary syndrome
• Smoking
• Sleeping on your back

However, how these health and lifestyle factors interact with each other or with genetic factors to influence the development of OSA is unclear [10].

Risk factors for CSA are [6, 7, 9]

• Age and gender: CSA is more likely from middle-age and more common in men
• Brain stem injury or structural defect
• Heart failure
• Low blood oxygen levels (hypoxia), e.g., when at high altitude.
• Medical conditions, including nervous system damage or disorders, e.g., amyotrophic lateral sclerosis (ALS, sometimes called Lou Gehrig’s disease), or the autoimmune disorder myasthenia gravis
• Opioid use
• Premature birth: before 37 weeks, with the risk decreasing with age
• Stroke
• Use of CPAP to treat OSA: may lead to treatment-emergent central sleep apnea/complex sleep apnea

How is sleep apnea diagnosed?

Tests for sleep apnea include monitoring in a sleep clinic where nocturnal polysomnography will record your movements and noises along with heart, lung, muscle and brain activity, chest and abdominal movements, airflow through mouth and nose, blood oxygen levels and heart rate [5].

For OSA, physicians will determine your apnea-hypopnea index (AHI) score—the number of breathing pauses per hour—to indicate the severity of your sleep apnea [5, 8].

What is the AHI?

The AHI is the total number of apneas and hypopneas of more than 10 seconds, divided by the sleep duration in hours. An apnea is defined as a reduction in airflow of at least 90% for a minimum of 10 seconds, and a hypopnea is described as a partial airway collapse that decreases airflow by more than 30% for at least 10 seconds [11]. Physicians use the AHI to categorize sleep apnea as mild, moderate or severe.

For adults, the categories of severity are

Mild: AHI between five and 14 apnea-hypopnea events per hour

Moderate: AHI between 15 and 30 apnea-hypopnea events per hour

Severe: AHI over 30 apnea-hypopnea events per hour

To understand the impact that this has on a person, we can multiply the number of events per hour by the sleep duration. This shows that someone with moderate sleep apnea who sleeps for 8 hours will have up to 239 apnea-hypopnea events in a night [4]. Remembering that these are episodes when they stop breathing and may wake up, the impact on the quality of sleep is clear.

In children, an AHI above one is enough for a diagnosis of OSA and the categories of severity are

Mild: AHI between one and five apnea-hypopnea events per hour

Moderate: AHI between six and 10 apnea-hypopnea events per hour

Severe: AHI of more than 10 apnea-hypopnea events per hour

The AIH score has limitations, as it does not measure how long the apnea or hypopnea lasts or how each event changes blood oxygen levels. Furthermore, it does not give any information about how breathing changes in relation to sleeping position, throughout the night, or over the course of several days [11].

Is sleep apnea genetic?

There is an approximate 50% increase in the likelihood of developing OSA if you have a first-degree relative with OSA [10]. Furthermore, your genes determine the shape and size of your head, face, jaw, and airways, as well as weight and where you store body fat, factors that can influence the development of OSA [12]. Therefore, although the exact causes or interactions that cause OSA are not always clear, some cases of OSA do have a genetic cause.

Candidate genes investigated by researchers trying to find the genetic cause of OSA:

• TNF-α, tumor necrosis factor-α: the −308G/A polymorphism is associated with increased levels of serum TNF-α in individuals with OSA; however, the polymorphism was also seen in control groups, suggesting that TNF-α alone does not cause OSA [13].
• PTGER3, prostaglandin E2 receptor EP3 subtype: a single nucleotide polymorphism in this gene has been associated with OSA in Europeans [13].
• LPAR1, lysophosphatidic acid receptor 1: a single nucleotide polymorphism in this gene has been associated with OSA in African Americans [13].
• GPR83, G-protein receptor gene: a polymorphism in this gene has been associated with AIH [13].
• ARRB1, β-arrestin 1 gene: variants were found to be associated with duration of apnea and hypopnea in women [13].

Candidate genes chosen to investigate the suggested relationship between sleep bruxism (teeth grinding) and OSA, which may occur concomitantly:

• DRD1, dopamine receptor encoding gene: a polymorphism in this gene may increase the likelihood of sleep bruxism (teeth grinding) [14].
• Serotonin receptor encoding gene (HTR2A): a polymorphism in this gene might contribute to the interaction between sleep bruxism and OSA [14].

Obesity is a known risk factor, and as up to 70% of people with OSA have obesity [10], there have been studies investigating genes related to factors like appetite control [13]. Studies that look at obesity and OSA can find it difficult to separate cause (obesity) from effect (OSA) [15]; however, there have been reports of genetic loci being associated with body mass index and OSA that warrant further investigation [16].

Genetic disorders that can cause obstructive sleep apnea

Certain disorders with a possible genetic component, such as polycystic ovary syndrome, myasthenia gravis, and mucopolysaccharidosis type I, may increase the likelihood of sleep apnea [3, 9, 10]. Cleft lip/palate is another example, and children with cleft lip/palate are more likely to have sleep apnea [9, 17].

Several genetic disorders increase the risk of OSA in children, including cerebral palsy, Prader-Willi syndrome, muscular dystrophy, and Down syndrome [12]. Down syndrome is a genetic disorder caused by an additional chromosome 21; it is also called trisomy 21. Due to the characteristic facial features of those with Down syndrome, and structural differences accompanied by low muscle tone, children with Down syndrome are more likely to have sleep apnea compared to children without Down syndrome. An estimated half to three quarters of all children with Down syndrome have sleep apnea. They are also more likely to have obesity, which is another risk factor for OSA [18].

There are also some neuromuscular disorders with genetic causes that have OSA and sleep-related hypoventilation as symptoms: Charcot-Marie-Tooth disease type 1, myotonic dystrophy type 1; facio-scapulo-humeral muscular dystrophy, Duchenne muscular dystrophy, and spinal and bulbar muscular atrophy [19].

Genetic disorders that can cause central sleep apnea

Central sleep apnea can occur if a person has a medical condition or injury involving the central nervous system, and in particular, that affects how the brain controls muscles in the chest and neck. This can also include genetic disorders. An example is ALS, a progressive neuromuscular disorder characterized by increasing muscle weakness and atrophy that can lead to breathing difficulties, which include central sleep apnea. As the disease progresses, the brain eventually loses its ability to control muscle movements and people with ALS are unable to breathe on their own. About 5-10% of cases of ALS are genetic [9, 20]. CSA has also been reported with myotonic dystrophy type 1 and mitochondrial disease [19]. However, CSA is considered less likely to be influenced by genetic factors than OSA [12].

In children, CSA has been reported due to the genetic disorders, Prader-Willi syndrome and Down syndrome, as well as the brain condition, Chiari malformation (also called Arnold-Chiari malformation) [12].

Is sleep apnea hereditary?

In most cases, it is unclear how the genetic changes that cause OSA are inherited [10]. By contrast, some of the genetic disorders that are known to cause OSA or CSA do have clear inheritance patterns that allow physicians to predict how likely it is that the disorder can be passed on to offspring.

Treatments for sleep apnea

Treatments for sleep apnea range from lifestyle changes to surgical interventions [3, 4]:

• Lose weight if necessary
• Take regular exercise
• Limit alcohol consumption
• Do not smoke
• Practice good sleep hygiene, which includes going to bed and waking up at the same time every day and not using electronic devices in bed
• Sleep on one side rather than on the back
• Use a continuous positive airway pressure (CPAP) machine, which pumps pressurized air into a mask worn over the nose or mouth during sleep and keeps airways open, prevents apnea, reduces snoring, and significantly decreases AHI: CPAP is the main treatment option for those with moderate or severe sleep apnea [3, 11]
• Wear a mandibular advancement device, which is like gum shield that keeps airways open during sleep
• Surgery to remove large tonsils or excess soft tissue, correct structural jaw problems, or help with weight loss

Consequences of untreated sleep apnea

Unfortunately, untreated sleep apnea can have a variety of consequences, including [8, 21]

• Complications with general anesthesia and surgery
• Depression and altered mood
• Extreme fatigue and tiredness
• High blood pressure
• Increased risk of stroke and heart disease
• Memory loss
• Metabolic syndrome
• Nonalcoholic fatty liver disease
• Type 2 diabetes

There is also an increased likelihood of accidents caused by extreme tiredness and performance at school or work may suffer.

Conclusion

Sleep apnea is a common, treatable sleep disorder. In mild cases, treatment involves lifestyle changes; while in moderate to severe cases, a CPAP machine is the treatment of choice. Untreated sleep apnea can have a range of consequences and treatment greatly improves quality of life.

The genetics of OSA are clearly complicated and although OSA has been the subject of a lot of genetic research, further work is necessary to define the genetic cause or gene interactions involved in the development of this common and often debilitating disorder. In particular, due to increasing cases of obesity and the clear association between it and OSA, genes involved in obesity are key targets for continued investigation.

The content of this article is for informational purposes only and is not intended to replace medical advice. Please visit your healthcare provider if you have concerns about your health and well-being.

References

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