Does Sleep Apnea Run in Families?

By Axelle Lavigne and Jordan Stern, MD. Axelle Lavigne is a medical student graduating from Imperial College London.

Summary

Children with snoring or sleep apnea are at risk of persistent sleep apnea as adults. If you are an adult who experienced breathing difficulties during childhood, it is important to reach out to your doctor to assess any lingering risk factors for obstructive sleep apnea (OSA). 

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Obstructive Sleep Apnea (OSA) occurs when your airway narrows or closes during sleep. This can happen in both children and adults and for a variety of different reasons. The subsequent drop in oxygen levels in your blood can have consequences on your health. In this article we will examine how sleep apnea can start from a young age and consequently continue to impact your life throughout adulthood, as well as looking at the effects OSA can have on other members of your family through genetic links.

Sleep apnea in children

Approximately 2 to 4% of children are affected by sleep apnea, usually beginning the ages of 2 and 8 years old [1]. The main symptoms can be separated into those experienced during the night and those experienced during the day. Nighttime symptoms include snoring (most common), parental reports of episodic pauses in breathing with movement of the chest and abdomen, or gasping, sweating and parasomnias. Daytime symptoms include morning headaches, excessive daytime sleepiness and a decline in the child’s cognitive abilities, which can be reflected on their performance at school. [2]

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In children, the risk of developing sleep apnea is higher when they exhibit specific characteristics that contribute to the condition. In the following section, we will discuss and elaborate on these features providing a comprehensive understanding of their impact on sleep apnea in children [3]:

1. Adenotonsillar hypertrophy

Most commonly, children with sleep apnea have adenotonsillar hypertrophy, which means that the soft tissues surrounding the airway - behind the tongue, at the back of the throat (tonsils) and behind the nose (adenoids) - are enlarged [4,5]. This results in a mechanical obstruction of the airway, which when combined with the relaxation of throat muscles during sleep, leads to sleep apnea [2]. The frequency of episodic apnea determines the severity of OSA. Typically, surgery is recommended where the tonsils and adenoids are removed, which works in 80% of cases. [1]

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Nevertheless, in cases where additional factors contribute to the narrowing of the airway during sleep, traditional surgical interventions may prove ineffective or only partially curative. These factors can hinder the success of standard surgery. Such factors include lingual lymphoid hypertrophy, which are soft tissues at the base of the tongue that are not removed during adenotonsillectomy. It has been shown recently that the pathogenesis of pediatric OSA could be linked to enlarged lingual tonsils, just like it is in adults. [3,6]

2. Obesity

When adenotonsillectomy for sleep apnea is performed on obese children, the success rate of surgery has been reported in some studies as low as 50% [7].

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OSA affects a significant proportion of obese children, with up to 60% being affected [2]. It is important to note that OSA and obesity are distinct conditions that often coexist, amplifying their respective adverse effects. The prevalence of obesity among children is rising globally, and it is occurring at earlier ages [8]. Each incremental increase in body mass index (BMI) above the 50th percentile is associated with approximately a 10% higher risk for developing OSAS [3].

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Both obesity and OSA have major impacts on children’s lives. A few of the most salient  features are listed below:

• Excessive daytime sleepiness [9]
• Decreased Quality Of Life [10]
• Neurocognitive function - resolution of OSA is associated with improved cognitive function including academic performance [11]
• Increased blood pressure - OSA is a trigger for hypertension in obese children [12,24]
• Increased cardiovascular and metabolic risk [1]

3. Craniofacial abnormalities

During sleep, the shape and position of the jaw play a significant role in determining one's ability to breathe properly. Inherited characteristics can predispose certain children to sleep apnea by reducing the available airway space. Notable features associated with this predisposition include mandibular retrognathia (displacement of the lower jaw towards the back), a longer facial profile, and a narrower jaw [13]. 

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There are also some rare clinical syndromes that are associated with sleep apnea, such as Down Syndrome, Prader-Willi and Beckwith-Wiedemann, Ehler-Danlos, Pierre Robin sequence and Noonan. Conditions affecting the respiratory centers in the brain may also cause sleep apnea. This happens in myelomeningoceles, Arnold Chiari malformations, brain injuries, tumours and surgery. [3] In these cases, surgery is performed to enlarge the airway by advancing the soft palate and tongue, a procedure called maxillo-mandibular advancement (MMA).

4. Allergic rhinitis

Allergic rhinitis leads to congestion, increased resistance in the upper airways and decreased airflow in the nasal cavities. It is important to rule out allergies as this is easily treatable and a relatively benign condition that can trigger sleep apnea. [3]

5. Inflammatory factors and biomarkers

Inflammation and oxidative stress has been linked in multiple studies to both adult and pediatric sleep apnea. The intermittent drop in oxygen blood levels triggers both local and systemic inflammation.

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Recent literature has established a connection between sleep apnea and the NF-κB pathway, which is a prominent inflammatory pathway in our bodies. Activation of this pathway leads to heightened expression of pro-inflammatory cytokines, including TNF-α, IL-6, and CRP. In adults, these cytokines contribute to the advancement of atherosclerosis and coronary heart disease. However, it is important to note that the confirmation of this association in children is still pending. [3]

Treatment of OSA in children

In cases where adenotonsillectomy proves unsuccessful or is contraindicated as a treatment for pediatric OSA; Positive Airway Pressure (PAP) therapy, similar to its application in adults, becomes a recommended alternative. Additionally, weight loss interventions are also considered as part of the treatment approach. This improves symptoms but simultaneously has positive effects on comorbid conditions, such as blood pressure which has been shown to decrease significantly post treatment. Reducing blood pressure is strongly associated with a marked reduction in cardiovascular events later in life. [2, 24] However, just like in adults, children may find it difficult to comply with such therapy due to complicated issues such as low self esteem, diverging from social norms and lack of confidence in PAP benefits. 

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Alternative treatment options for pediatric OSA include the use of oral appliances that help advance the position of the jaw and enhance the upper airway space. While certain studies provide support for the effectiveness of oral appliances in children, others do not reach the same conclusion [1]. As a result, the current evidence remains inconclusive regarding the efficacy of oral appliances specifically for children [14].

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In contrast, these treatments have been proven to be effective in adults and show similar and sometimes superior compliance when compared with CPAP therapy.

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Positional therapy, which involves keeping someone on their side during sleep, improves the AHI (a number which indicates the average number of reduced breathing events per hour and correlates with sleep apnea severity) in adults; however there is lack of concurrent evidence in children [15]. Hypoglossal nerve stimulation, a novel therapy, also lacks the necessary long term and short term evidence in children to make definitive conclusions about its use. [1]

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To date, a randomized controlled trial, which represents the highest level of evidence in assessing treatment efficacy, has not been conducted in children to determine the superiority of different treatment options. This highlights the need for further research and comprehensive studies in pediatric populations.

What this means for adult populations

75% of obese children become obese adults [16]. This means that people carry the increased risk of OSA into adulthood.

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The following groups of children are at an elevated risk of persisting with OSA as they advance in age [17]:

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• Higher baseline BMI correlated with lower cure rates
• Male sex alone was a risk factor for incident OSA, whereas being female showed a higher complete remission rate in adulthood
• Children diagnosed at a later age (more than 10 years old) were more likely to have persistent OSA into adulthood
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It has been shown that young adults with severe OSA in childhood had on average a significantly higher BMI, fewer academic degrees and snored more compared to young adults with no sleep apnea. [18]

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If you are an adult who experienced breathing difficulties during childhood, it is important to reach out to your doctor to assess any lingering risk factors for obstructive sleep apnea (OSA). Similarly, if your child has been diagnosed with OSA, it implies a potential predisposition to the condition within your family, and you should consider undergoing a sleep test for evaluation. By proactively addressing these concerns and seeking appropriate medical guidance, you can better understand and manage the risk of OSA for both yourself and your child.

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In addition, there is both a direct and indirect link between OSA and genetics. Direct genetic links involve the presence of multiple genes that have been scientifically proven to contribute directly to an increased incidence of sleep apnea. These specific genes play a role in predisposing individuals to the development of sleep apnea when they possess them. Indirect links include features which are heritable and predisposed to sleep apnea. These include the shape of your face, mouth and throat, how your brain controls your throat and jaw muscles while you sleep, as well as your circadian rhythm, which controls how much and when you sleep or wake up. [19] The response your body has to decreased oxygen levels during an apnea episode are also under genetic influence. 30-70% of phenotypic variance can be explained by shared familial factors [13, 20, 21, 22, 23]

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In the context of OSA, there is no straightforward inheritance pattern or single gene that can accurately predict an increased risk of developing the condition. Inheritable factors for OSA involve multiple sets of genes inherited from both parents. Therefore, it is the collective influence of various genetic components rather than a single gene that contributes to the risk of OSA.

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Research has indicated that approximately 40% of the variance in AHI can be attributed to genetic factors. [15] These findings suggest that genetic factors play a significant role in OSA disease severity. [20] Moreover if your parent or sibling has sleep apnea, your own risk of developing the condition is increased by 50%. Several genes have been specifically identified to cause sleep apnea, including the ApoE4 allele, TNFa 308G gene polymorphism, NADPH polymorphism. [3]

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