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Contemporary Reviews in Sleep Medicine |

Sleep-Disordered Breathing in Down SyndromeSleep Apnea and Down Syndrome FREE TO VIEW

Chitra Lal, MD, FCCP; David R. White, MD; Jane E. Joseph, PhD; Karen van Bakergem, LMSW; Angela LaRosa, MD
Author and Funding Information

From the Department of Pulmonary, Critical Care, Allergy, and Sleep Medicine (Dr Lal), the Department of Pediatric Otolaryngology (Dr White), the Department of Neurosciences (Dr Joseph), and the Department of Pediatrics, Division of Developmental-Behavioral Pediatrics (Ms van Bakergem and Dr LaRosa), Medical University of South Carolina, Charleston, SC.

CORRESPONDENCE TO: Chitra Lal, MD, FCCP, Department of Pulmonary, Critical Care, Allergy, and Sleep Medicine, Medical University of South Carolina, 96 Jonathan Lucas St, CSB Ste 812, MSC 630, Charleston, SC 29425; e-mail: lalch@musc.edu


Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2015;147(2):570-579. doi:10.1378/chest.14-0266
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OSA is associated with significant adverse outcomes with far-reaching health-care implications. OSA is much more common and severe in patients with Down syndrome (DS) than in the general population, yet there is a striking lack of literature in this area. In this review article, we have summarized the current state of knowledge and presented the available data on OSA in DS. The higher prevalence and severity of OSA in patients with DS may be related to unique upper airway anatomic features as well as increased risk for obesity, hypothyroidism, gastroesophageal reflux disease, and generalized hypotonia. Although many of the manifestations of OSA in patients with DS are similar to those seen in the general population, the relative morbidity is significantly higher. For individuals with DS who already face cognitive challenges, the added impact of OSA on cognitive function may hinder their ability to function independently and reach their full potential. Screening and evaluation for OSA should be done in children and adults with DS. Treatment of OSA in DS involves the use of CPAP, upper airway surgery, and dental appliances, along with weight-reduction strategies, nasal steroids, and oral leukotriene modifiers as adjunctive treatments. The treatment plan should be individualized for each patient with DS, taking into account age, comorbid conditions, and barriers to treatment adherence. Future research should aim to better characterize OSA, further evaluate neurocognitive outcomes, and evaluate the efficacy of treatments in patients with DS.

Figures in this Article

Sleep-disordered breathing (SDB) refers to a group of disorders characterized by abnormalities of respiration and/or ventilation during sleep. It encompasses central sleep apnea (CSA) syndromes, OSA disorders, sleep-related hypoventilation disorders, and sleep-related hypoxemia disorder.1 OSA is the commonest of these disorders and has been associated with significant adverse impacts on health, such as stroke, coronary artery disease, hypertension, arrhythmias, and excessive daytime sleepiness resulting in an increased risk of motor vehicle accidents.2-5 It is increasingly being recognized that OSA is associated with memory impairment and deterioration in other aspects of cognitive functioning.6

Down syndrome (DS), defined by an extra copy of chromosome 21, is the commonest genetic disorder, occurring in one out of 691 births.7 Individuals with DS are at an increased risk of heart defects, gastroesophageal reflux, celiac disease, hypothyroidism, hearing and vision problems, leukemia, and Alzheimer disease (AD), as well as intellectual disability of varying degrees.

The prevalence of OSA in children with DS is 30% to 50% and increases to > 90% in adults with DS, as compared with the 2% to 4% prevalence seen in the general population.8-10 In addition, OSA is usually more severe in patients with DS, with significant hypoxemia as compared with individuals without DS.10 Several manifestations of OSA, such as cognitive impairment and cardiovascular disease, are common in individuals with DS, which may obscure the diagnosis of OSA in patients with DS. Thus, clinicians should maintain a high index of suspicion for OSA in patients with DS.

Adults with DS also have a very high risk of developing AD.11 The added insult of OSA in this highly vulnerable population may exacerbate cognitive difficulties and lead to a greater predisposition to neurodegeneration.

Patients with DS now lead longer and more productive lives. Early recognition and aggressive treatment of OSA in patients with DS can further help to improve quality of life. Despite the significant resources that have been allocated to the study of OSA in the general population, few studies have evaluated the impact of OSA on patients with DS, and available studies are limited by small sample size.

Although not a systematic review, the purpose of this article is to provide a comprehensive review of this topic with a focus on recent developments in the field. Keywords such as “Down syndrome sleep disordered breathing” and “obstructive sleep apnea,” and specifıc topics such as “cognitive functioning,” “Alzheimer disease,” and “executive functioning,” and databases including PubMed, CINAHL, PsycINFO, and MEDLINE were used in searches, which were limited to English language. In addition to computer searches, the ancestry approach was used. An important goal of this article is to identify published information specific to OSA in individuals with DS; however, given the limited amount of research on OSA in those with DS, evidence regarding OSA in the general population is discussed to make recommendations for further research. Salient studies specifically addressing OSA in patients with DS are listed in Table 1.8,10,12-28

Table Graphic Jump Location
TABLE 1 ]  Salient Studies on OSA in Patients With DS

AT = adenotonsillectomy; DS = Down syndrome; EF = executive functioning; ENT = ear, nose, throat; HTN = hypertension; PSG = polysomnogram; RME = rapid maxillary expansion; RPM = Raven Progressive Matrices; SDB = sleep-disordered breathing; UA = upper airway.

a 

Twenty-two patients with DS, 22 matched control subjects.

b 

Eleven patients with DS, 9 children without DS.

c 

Eighty-seven children with DS; 64 matched for age, sex, year of surgery.

Patients with DS are predisposed to upper airway obstruction due to multiple factors (Fig 1). Midface and maxillary hypoplasia have been demonstrated radiologically, resulting in smaller bony dimensions of the airway.12,29 Although absolute tongue size is normal, relative macroglossia results because of the smaller bony framework of the small maxilla and mandible. Donnelly et al13 demonstrated on cine MRI that this relative macroglossia and hypotonia resulted in airway obstruction caused by glossoptosis and hypopharyngeal collapse (also referred to as pharyngomalacia) in nearly two-thirds of children with DS and persistent OSA after adenotonsillectomy (AT). A follow-up study revealed that lingual tonsillar hypertrophy is > 10 times more common in children with DS compared with other children with OSA, further contributing to obstruction at the oropharyngeal level.30 Hypotonia may also cause obstruction at the supraglottic level, with laryngomalacia being demonstrated in nearly 50% of children with DS and upper airway obstructive symptoms.14 Subglottic and tracheal stenosis are more common in patients with DS than other populations.15,31

Figure Jump LinkFigure 1 –  Upper airway anatomic features predisposing to OSA in patients with Down syndrome.Grahic Jump Location

The association between obesity and OSA in individuals with DS has been demonstrated in several studies.10,16,17 In a Dutch sample, children with DS were almost twice as likely to be overweight and obese as compared with a control group (25% of boys and 32% of girls with DS were overweight, and 4% of boys and 5% of girls were obese).32 Women and men with DS were more likely to be overweight, with women more likely to be obese when compared with matched control subjects.33 It is postulated that fat deposits in the lateral wall of the pharynx reduce the caliber of the upper airway and increase airway collapsibility. Central obesity, defined as increased intraabdominal and subcutaneous fat as measured by waist circumference, has been associated with OSA.34,35 Individuals with DS have a higher incidence of central adiposity; however, the actual prevalence relative to the typical population needs further study. In another study, the apnea-hypopnea index (AHI) was found to be highly correlated with the degree of obesity in adults with DS.10 Obesity is a risk factor for OSA and is more prevalent in patients with DS; thus, it has been suggested that OSA severity in those with DS may be correlated with obesity.10,36 Therefore, obesity as a risk factor for OSA should be discussed with all patients with DS.

Higher rates of gastroesophageal reflux disease are seen in patients with DS, which can lead to inflammation and obstruction of the upper airway, thus increasing risk of developing OSA.37,38 An increased OSA prevalence of 25% to 35% has been reported in the general population in patients with hypothyroidism.39,40 This association may be mediated through narrowing of the pharynx due to soft tissue infiltration by mucopolysaccharides and proteins.41 Altered regulatory control of pharyngeal dilator muscles due to neuropathy may also be involved.41 Appropriate treatment of hypothyroidism can improve and occasionally cure OSA in studies in the general population.39 Thyroid disease occurs more often in patients with DS (4%-18%), with the risk increasing with age.42 Thus, in all patients with DS, thyroid studies are recommended every 6 months until 1 year of age and then annually thereafter. Normal thyroid function or appropriate thyroid management should be verified in individuals with DS presenting with OSA.

Infants with DS have been shown to have a higher prevalence of pulmonary hypertension.43 Alveolar capillary dysplasia and increased pulmonary vascular resistance have been reported in infants with DS.44-46 Pulmonary hypertension and cor pulmonale have also been associated with OSA in patients with DS.47,48 It has further been shown that relief of the upper airway obstruction could reverse the pulmonary hypertension in children with DS.48 Thus, cardiovascular consequences of OSA are likely to be even more dangerous in patients with DS as compared with patients without DS.

Common Symptoms of OSA in Children and Adults With DS

The manifestations and long-term sequelae of OSA in patients with DS are listed in Tables 2 and 3. Although many of the cardinal symptoms of OSA, such as snoring, fatigue, and restless sleep, are common to both children and adults with DS and OSA, children may also present with failure to thrive, hyperactivity, behavioral disruptions, and poor school performance, whereas adults may present with mood dysregulation and depression.49-52

Table Graphic Jump Location
TABLE 2 ]  Common Symptoms and Sequelae of OSA in Adults With DS

See Table 1 legend for expansion of abbreviation.

Table Graphic Jump Location
TABLE 3 ]  Common Symptoms and Sequelae of OSA in Children with DS

See Table 1 legend for expansion of abbreviation.

Cognitive Impairment, DS, and OSA: A Triple Threat

Studies have found that decreased slow-wave sleep is seen in children and adolescents with DS who have OSA and that OSA might explain some of the variability associated with verbal IQ, memory, and executive function (EF) in a DS community cohort.18,53,54 Another study found that among children with DS, those with comorbid OSA performed worse on verbal IQ and cognitive flexibility tasks than those without OSA.19 EF, which is regulated in the prefrontal cortex, helps to integrate, plan, and organize information to complete a goal-directed task. The prefrontal cortex also regulates working memory, attention, processing speed, arousal, and inhibition. It is hypothesized that the intermittent episodic hypoxemia of OSA and decreased slow-wave sleep can disrupt prefrontal cortical function and thus impact EF. A study of 29 adolescents and young adults with DS found that parents’ rating of OSA and sleep disruption was an independent predictor of executive dysfunction in these subjects.18 However, this study was limited by the fact that OSA was not confirmed by polysomnogram (PSG).

Patients with DS are particularly predisposed to developing early-onset AD after the age of 35 years.55 The prevalence of AD in DS increases to 75% by the age of 65 years.11 Oxidative stress has been implicated in the pathogenesis of premature AD in patients with DS.56 Oxidative stress is also a major player in OSA, given the intermittent, episodic hypoxemia and hypoxia-reperfusion injury associated with it.57 One could speculate that the added insult of OSA may accelerate the cognitive decline in patients with DS.18 This is an area that needs to be explored further in research studies.

Another study found that a higher number of apneas in patients with DS was associated with greater deficiencies in visuoperceptual skills, including orientation, of the right brain hemisphere.20 The presence of snoring in children with DS has been associated with a higher prevalence of disruptive school behavior as compared with nonsnoring children with DS.50 OSA is a common comorbid condition in adolescents and young adults with DS and depression and may cause further functional decline in patients with DS.52 Attention deficit hyperactivity disorder, which is more common in the DS population than in the general population (9% vs 3% to 7%), has been associated with OSA.58,59 The presence of OSA in individuals with DS can result in poorer school performance, limited social interactions, and impairment in activities of daily living, thus significantly decreasing quality of life.

Diagnosis of OSA in DS

Clinical history is helpful in the diagnosis of OSA in patients with DS. However, absence of symptoms does not obviate the need for a PSG, which is the diagnostic test of choice. Screening oximetry has poor sensitivity for diagnosing OSA in subjects with DS and should not be used as a stand-alone test for diagnosing OSA.21 Unattended portable monitoring for the diagnosis of OSA has not been evaluated specifically in patients with DS. Thus, we would not recommend using this as a diagnostic modality in patients with DS.

One study found that 97% of children with DS who snored had OSA.60 This study included 33 children with a mean age of 4.9 years, and none had previously undergone AT. On the other hand, not all children with DS who have OSA are habitual snorers.22 Given the unique medical and developmental needs of children with DS, specific health supervision guidelines for this patient population have been published.42 These recommend that at least once during the first 6 months of life, providers should discuss OSA symptoms with parents, including heavy breathing, snoring, uncommon sleep positions, frequent nighttime awakenings, daytime sleepiness, apneic pauses, and behavior problems. If any of these symptoms is endorsed, referral to a physician with expertise in pediatric sleep disorders is recommended. This history should be reviewed at every well-child visit. Parental reports of OSA symptoms and results of PSG do not always correlate; hence, it is recommended that all children with DS should have a sleep study by 4 years of age regardless of symptoms.61,23 It is our practice at the Medical University of South Carolina’s Down Syndrome Center to repeat a PSG at 8 years of age in children with DS given the high risk, lack of symptom correlation, and potential long-term sequelae of untreated OSA; however, published guidelines for OSA screening in older children are not available. A recently published article looking specifically at OSA in 8-year-old children with DS found a significantly higher prevalence of moderate to severe OSA when compared with the general population.24 Additional PSG testing is recommended outside of this age range if symptoms of OSA are present.

Treatment of OSA in DS
Nonsurgical Treatments:

Habitual snoring has been shown to be associated with smoking, environmental pollution, atopy, and viral infections.62 Thus, simple measures like avoidance of noxious fumes and treatment of nasal allergies with antihistamines and intranasal steroids such as budesonide can decrease the severity of snoring.63 Oral leukotriene modifiers such as montelukast can improve milder forms of SDB.64 In a case series, oral care and treatment of xerostomia in three children with OSA and DS caused resolution of the snoring and apneas.65 The exact mechanism of the association between xerostomia and OSA is unknown.

Weight loss by exercise and dietary programs may help decrease OSA severity in individuals with DS. In patients with DS and OSA, thyroid function should be checked and hypothyroidism should be treated.

Positive airway pressure (PAP) remains the cornerstone of treatment of OSA in adults, and this is also true for adults with DS. PAP can be applied as CPAP or bilevel PAP(BPAP). Patients with DS represent a unique and challenging group, however, as far as PAP compliance is concerned. At least one study has shown that of the nine adults with DS who were prescribed CPAP, five had excellent compliance.10 Improvements in daytime functioning and excessive daytime sleepiness were seen in CPAP-compliant patients in this study. Cognitive behavioral therapy may be used to improve PAP compliance in patients with DS, although large studies in this regard are lacking. Other measures that can be taken to improve PAP adherence include more “hands-on” education for patients and caregivers, and clinic and telephone follow-up.66,67

Dental appliances are useful in treating mild to moderate OSA in the general population. However, they have not been studied specifically in patients with DS. Dental appliances can be tongue-retaining devices, which retain the tongue in a forward position using a suction cup or mandibular advancing devices. Although tongue-retaining devices may be somewhat difficult for patients with DS to tolerate, mandibular advancing devices may be a viable treatment option for mild to moderate OSA in patients with DS.68 The efficacy of dental appliances for treatment of OSA is considerably less than that of CPAP, with only a 50% to 60% reduction in the respiratory disturbance index, but patient compliance is better than with CPAP.69 Given the upper airway obstruction at multiple levels in patients with DS, it is possible that dental appliances maybe less efficacious in these patients than in the general population. Dental appliances should be custom made for each individual patient and may not be appropriate in young children with immature dentition or ongoing facial growth.

Surgical Treatments:

The first-line surgical treatment of OSA in children is AT. In children with DS, AT is effective in reducing obstructive AHI but usually does not normalize it.25 Sleep-related hypoxia and hypercapnia resolve even less frequently.25,70 In fact, no postoperative change in arterial oxygen saturation nadir was noted by Shete et al25 in 11 children with DS who underwent AT. Goldstein et al26 noted a respiratory complication rate five times higher than control subjects in children with DS undergoing AT, along with a prolonged recovery of adequate oral intake. Mortality after AT is reported at between one in 10,000 and one in 30,000 in the general population, with most episodes related to respiratory events.71 Mortality figures specific to patients with DS undergoing tonsillectomy have not been reported. DS as a separate risk factor is difficult to separate from other risk factors, such as obesity and severe sleep apnea, which have been shown to increase posttonsillectomy complication rates. In any case, a thorough airway evaluation and a sleep study should be performed before AT in patients with DS.72 Since comorbidities, craniofacial abnormalities, and moderate to severe OSA are all considered indications for postoperative hospital observation in children undergoing AT, children with DS should be observed in the hospital (intensive care unit if obesity and/or severe OSA are present) after AT in contrast to their peers who are generally managed as outpatients.73 Because of the high rate of persistent OSA in children with DS, a postoperative sleep study is indicated 2 to 3 months after AT.

Children who have persistent OSA after AT should undergo additional airway evaluation, since airway abnormalities in this population are complex and may include multiple levels of obstruction. Surgical management is typically driven by outcomes from studies such as sleep endoscopy and cine MRI, both of which may be used to evaluate the entire airway during a state of induced sleep, to identify sites of dynamic airway collapse.

Lateral pharyngoplasty (tonsillar pillar plication) has been shown to be no better than AT alone.70 Uvulopalatopharyngoplasty was shown to reduce AHI from 27 to 9 in five children with DS, but it is not clear whether any patients had resolution of OSA.74 Combined genioglossus advancement and radiofrequency ablation of the tongue base was demonstrated to reduce AHI below 5 in 12 of 19 patients, with concomitant improvement of hypoxia and hypercapnia.75 Lingual tonsillar hypertrophy is more common in children with DS who have persistent OSA after AT than control subjects with the same history, but to date there is no study comparing preoperative sleep studies to postoperative results after lingual tonsillectomy.30,76

In patients with nasal obstruction, inferior turbinate reduction and revision adenoidectomy may be indicated. In adults and older children, septoplasty may be indicated as well. Maxillary (palatal) expansion may be indicated, especially in patients with severe maxillary hypoplasia.27 Supraglottoplasty, a procedure whereby redundant collapsing tissue is removed endoscopically from the supraglottis, may be indicated to address severe laryngomalacia. Subglottic and tracheal stenosis may be amenable to reconstructive procedures. Mandibular distraction osteogenesis is a procedure used to lengthen the mandible, which may be useful in patients with micrognathia. The resultant forward movement of the tongue base widens the oropharyngeal airway. There is, however, no substantial literature examining the outcomes of these procedures specifically in patients with DS and OSA. In instances of persistent severe OSA not amenable to other treatment, tracheostomy may be necessary. A treatment algorithm for children and adults with DS is outlined in Figure 2.

Figure Jump LinkFigure 2 –  Treatments for sleep-disordered breathing in children and adults with Down syndrome.Grahic Jump Location

Congenital central hypoventilation syndrome, characterized by the presence of PHOX2B gene, has been associated with DS and Hirschsprung disease.77 This rare disorder mandates lifelong mechanical ventilation, as patients do not breathe during sleep, despite progressive hypoxia and hypercapnia. Less catastrophic CSA can also be seen in patients with DS. CSA has been reported to constitute 10.8% (in patients with no upper airway abnormalities) to 89.4% of all respiratory events during sleep in patients with DS. CSA is treated with PAP, such as CPAP, BPAP, BPAP with a backup rate (BPAP ST mode), and adaptive servoventilation.28,78 As patients with DS age, the preponderance of respiratory events may become obstructive in nature because of increasing narrowing of the upper airway.28

The literature to date suggests that OSA prevalence and long-term sequelae are greater in those with DS than in the general population; however, further research is needed to better define specific risk factors, outcomes, and evidence-based treatment approaches for this potentially modifiable condition.

The full impact of OSA on cognitive functioning in patients with DS needs to be further explored via standardized measures of cognition. Improved identification and treatment of OSA in patients with DS may have long-term effects that could decrease the risk of developing AD. Given the unique pathophysiology seen in those with DS, large studies evaluating the efficacy of current treatment modalities for OSA and new treatment modalities should be undertaken. Prompt diagnosis and treatment of OSA may help to improve the overall quality of life and longevity in patients with DS.

Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Lal has received grant funding from Invado Pharmaceuticals. Dr White has received grant funding from Otonomy Inc. Drs Joseph and LaRosa and Ms van Bakergem have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Other contributions: We thank Emma Vought, MS; Michelle DiBartolo, BS; and Xun Zhu, PhD, for their contributions in the preparation of this manuscript.

AD

Alzheimer disease

AHI

apnea-hypopnea index

AT

adenotonsillectomy

BPAP

bilevel positive airway pressure

CSA

central sleep apnea

DS

Down syndrome

EF

executive function

PAP

positive airway pressure

PSG

polysomnogram

SDB

sleep-disordered breathing

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Rubin SS, Rimmer JH, Chicoine B, Braddock D, McGuire DE. Overweight prevalence in persons with Down syndrome. Ment Retard. 1998;36(3):175-181. [CrossRef] [PubMed]
 
Macchini F, Leva E, Torricelli M, Valadè A. Treating acid reflux disease in patients with Down syndrome: pharmacological and physiological approaches. Clin Exp Gastroenterol. 2011;4:19-22. [CrossRef] [PubMed]
 
May JG, Shah P, Lemonnier L, Bhatti G, Koscica J, Coticchia JM. Systematic review of endoscopic airway findings in children with gastroesophageal reflux disease. Ann Otol Rhinol Laryngol. 2011;120(2):116-122. [CrossRef] [PubMed]
 
Attal P, Chanson P. Endocrine aspects of obstructive sleep apnea. J Clin Endocrinol Metab. 2010;95(2):483-495. [CrossRef] [PubMed]
 
Lin CC, Tsan KW, Chen PJ. The relationship between sleep apnea syndrome and hypothyroidism. Chest. 1992;102(6):1663-1667. [CrossRef] [PubMed]
 
Devdhar M, Ousman YH, Burman KD. Hypothyroidism. Endocrinol Metab Clin North Am. 2007;36(3):595-615. [CrossRef] [PubMed]
 
Bull MJ; Committee on Genetics. Health supervision for children with Down syndrome. Pediatrics. 2011;128(2):393-406. [CrossRef] [PubMed]
 
Cua CL, Blankenship A, North AL, Hayes J, Nelin LD. Increased incidence of idiopathic persistent pulmonary hypertension in Down syndrome neonates. Pediatr Cardiol. 2007;28(4):250-254. [CrossRef] [PubMed]
 
Galambos C. Alveolar capillary dysplasia in a patient with Down’s syndrome. Pediatr Dev Pathol. 2006;9(3):254-255. [CrossRef] [PubMed]
 
Shehata BM, Abramowsky CR. Alveolar capillary dysplasia in an infant with trisomy 21. Pediatr Dev Pathol. 2005;8(6):696-700. [CrossRef] [PubMed]
 
Chi TL, Krovetz LJ. The pulmonary vascular bed in children with Down syndrome. J Pediatr. 1975;86(4):533-538. [CrossRef] [PubMed]
 
Loughlin GM, Wynne JW, Victorica BE. Sleep apnea as a possible cause of pulmonary hypertension in Down syndrome. J Pediatr. 1981;98(3):435-437. [CrossRef] [PubMed]
 
Levine OR, Simpser M. Alveolar hypoventilation and cor pulmonale associated with chronic airway obstruction in infants with Down syndrome. Clin Pediatr (Phila). 1982;21(1):25-29. [CrossRef] [PubMed]
 
Freezer NJ, Bucens IK, Robertson CF. Obstructive sleep apnoea presenting as failure to thrive in infancy. J Paediatr Child Health. 1995;31(3):172-175. [CrossRef] [PubMed]
 
Carskadon MA, Pueschel SM, Millman RP. Sleep-disordered breathing and behavior in three risk groups: preliminary findings from parental reports. Childs Nerv Syst. 1993;9(8):452-457. [CrossRef] [PubMed]
 
Rosen D. Management of obstructive sleep apnea associated with Down syndrome and other craniofacial dysmorphologies. Curr Opin Pulm Med. 2011;17(6):431-436. [PubMed]
 
Capone GT, Aidikoff JM, Taylor K, Rykiel N. Adolescents and young adults with Down syndrome presenting to a medical clinic with depression: co-morbid obstructive sleep apnea. Am J Med Genet A. 2013;161A(9):2188-2196. [CrossRef] [PubMed]
 
Edgin JO, Pennington BF, Mervis CB. Neuropsychological components of intellectual disability: the contributions of immediate, working, and associative memory. J Intellect Disabil Res. 2010;54(5):406-417. [CrossRef] [PubMed]
 
Fernandez F, Edgin JO. Poor sleep as a precursor to cognitive decline in Down syndrome: a hypothesis. J Alzheimers Dis Parkinsonism. 2013;3(2):124. [PubMed]
 
Rossor MN, Fox NC, Mummery CJ, Schott JM, Warren JD. The diagnosis of young-onset dementia. Lancet Neurol. 2010;9(8):793-806. [CrossRef] [PubMed]
 
Muchová J, Zitňanová I, Duračková Z. Oxidative stress and Down syndrome. Do antioxidants play a role in therapy? Physiol Res. 2014;63(5):535-542. [PubMed]
 
Lavie L. Obstructive sleep apnoea syndrome—an oxidative stress disorder. Sleep Med Rev. 2003;7(1):35-51. [CrossRef] [PubMed]
 
Gath A, Gumley D. Behaviour problems in retarded children with special reference to Down’s syndrome. Br J Psychiatry. 1986;149:156-161. [CrossRef] [PubMed]
 
Sedky K, Bennett DS, Carvalho KS. Attention deficit hyperactivity disorder and sleep disordered breathing in pediatric populations: a meta-analysis. Sleep Med Rev. 2014;18(4):349-356. [CrossRef] [PubMed]
 
Fitzgerald DA, Paul A, Richmond C. Severity of obstructive apnoea in children with Down syndrome who snore. Arch Dis Child. 2007;92(5):423-425. [CrossRef] [PubMed]
 
Ng DK, Chan CH, Cheung JM. Children with Down syndrome and OSA do not necessarily snore. Arch Dis Child. 2007;92(11):1047-1048. [PubMed]
 
Kuehni CE, Strippoli MP, Chauliac ES, Silverman M. Snoring in preschool children: prevalence, severity and risk factors. Eur Respir J. 2008;31(2):326-333. [CrossRef] [PubMed]
 
Kheirandish-Gozal L, Gozal D. Intranasal budesonide treatment for children with mild obstructive sleep apnea syndrome. Pediatrics. 2008;122(1):e149-e155. [CrossRef] [PubMed]
 
Goldbart AD, Goldman JL, Veling MC, Gozal D. Leukotriene modifier therapy for mild sleep-disordered breathing in children. Am J Respir Crit Care Med. 2005;172(3):364-370. [CrossRef] [PubMed]
 
Sato K, Shirakawa T, Niikuni N, Sakata H, Asanuma S. Effects of oral care in Down syndrome children with obstructive sleep apnea. J Oral Sci. 2010;52(1):145-147. [CrossRef] [PubMed]
 
Likar LL, Panciera TM, Erickson AD, Rounds S. Group education sessions and compliance with nasal CPAP therapy. Chest. 1997;111(5):1273-1277. [CrossRef] [PubMed]
 
Smith CE, Dauz ER, Clements F, et al. Telehealth services to improve nonadherence: a placebo-controlled study. Telemed J E Health. 2006;12(3):289-296. [CrossRef] [PubMed]
 
Waldman HB, Hasan FM, Perlman S. Down syndrome and sleep-disordered breathing: the dentist’s role. J Am Dent Assoc. 2009;140(3):307-312. [CrossRef] [PubMed]
 
Lim J, Lasserson TJ, Fleetham J, Wright J. Oral appliances for obstructive sleep apnoea. Cochrane Database Syst Rev. 2003;; (4):CD004435.
 
Merrell JA, Shott SR Sr. OSAS in Down syndrome: T&A versus T&A plus lateral pharyngoplasty. Int J Pediatr Otorhinolaryngol. 2007;71(8):1197-1203. [CrossRef] [PubMed]
 
Goldman JL, Baugh RF, Davies L, et al. Mortality and major morbidity after tonsillectomy: etiologic factors and strategies for prevention. Laryngoscope. 2013;123(10):2544-2553. [PubMed]
 
Roland PS, Rosenfeld RM, Brooks LJ, et al; American Academy of Otolaryngology—Head and Neck Surgery Foundation. Clinical practice guideline: polysomnography for sleep-disordered breathing prior to tonsillectomy in children. Otolaryngol Head Neck Surg. 2011;145(suppl 1):S1-S15. [CrossRef] [PubMed]
 
Baugh RF, Archer SM, Mitchell RB, et al; American Academy of Otolaryngology-Head and Neck Surgery Foundation. Clinical practice guideline: tonsillectomy in children. Otolaryngol Head Neck Surg. 2011;144(suppl 1):S1-S30. [CrossRef] [PubMed]
 
Wiet GJ, Bower C, Seibert R, Griebel M. Surgical correction of obstructive sleep apnea in the complicated pediatric patient documented by polysomnography. Int J Pediatr Otorhinolaryngol. 1997;41(2):133-143. [CrossRef] [PubMed]
 
Wootten CT, Shott SR. Evolving therapies to treat retroglossal and base-of-tongue obstruction in pediatric obstructive sleep apnea. Arch Otolaryngol Head Neck Surg. 2010;136(10):983-987. [CrossRef] [PubMed]
 
Sedaghat AR, Flax-Goldenberg RB, Gayler BW, Capone GT, Ishman SL. A case-control comparison of lingual tonsillar size in children with and without Down syndrome. Laryngoscope. 2012;122(5):1165-1169. [CrossRef] [PubMed]
 
Jones KL, Pivnick EK, Hines-Dowell S, et al. A triple threat: Down syndrome, congenital central hypoventilation syndrome, and Hirschsprung disease. Pediatrics. 2012;130(5):e1382-e1384. [CrossRef] [PubMed]
 
Ferri R, Curzi-Dascalova L, Del Gracco S, Elia M, Musumeci SA, Stefanini MC. Respiratory patterns during sleep in Down’s syndrome: importance of central apnoeas. J Sleep Res. 1997;6(2):134-141. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1 –  Upper airway anatomic features predisposing to OSA in patients with Down syndrome.Grahic Jump Location
Figure Jump LinkFigure 2 –  Treatments for sleep-disordered breathing in children and adults with Down syndrome.Grahic Jump Location

Tables

Table Graphic Jump Location
TABLE 1 ]  Salient Studies on OSA in Patients With DS

AT = adenotonsillectomy; DS = Down syndrome; EF = executive functioning; ENT = ear, nose, throat; HTN = hypertension; PSG = polysomnogram; RME = rapid maxillary expansion; RPM = Raven Progressive Matrices; SDB = sleep-disordered breathing; UA = upper airway.

a 

Twenty-two patients with DS, 22 matched control subjects.

b 

Eleven patients with DS, 9 children without DS.

c 

Eighty-seven children with DS; 64 matched for age, sex, year of surgery.

Table Graphic Jump Location
TABLE 2 ]  Common Symptoms and Sequelae of OSA in Adults With DS

See Table 1 legend for expansion of abbreviation.

Table Graphic Jump Location
TABLE 3 ]  Common Symptoms and Sequelae of OSA in Children with DS

See Table 1 legend for expansion of abbreviation.

References

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Shires CB, Anold SL, Schoumacher RA, Dehoff GW, Donepudi SK, Stocks RM. Body mass index as an indicator of obstructive sleep apnea in pediatric Down syndrome. Int J Pediatr Otorhinolaryngol. 2010;74(7):768-772. [CrossRef] [PubMed]
 
Chen CC, Spanò G, Edgin JO. The impact of sleep disruption on executive function in Down syndrome. Res Dev Disabil. 2013;34(6):2033-2039. [CrossRef] [PubMed]
 
Breslin J, Spanò G, Bootzin R, Anand P, Nadel L, Edgin J. Obstructive sleep apnea syndrome and cognition in Down syndrome. Dev Med Child Neurol. 2014;56(7):657-664. [CrossRef] [PubMed]
 
Andreou G, Galanopoulou C, Gourgoulianis K, Karapetsas A, Molyvdas P. Cognitive status in Down syndrome individuals with sleep disordered breathing deficits (SDB). Brain Cogn. 2002;50(1):145-149. [CrossRef] [PubMed]
 
Jheeta S, McGowan M, Hadjikoumi I. Is oximetry an effective screening tool for obstructive sleep apnoea in children with Down syndrome? Arch Dis Child. 2013;98(2):164. [CrossRef] [PubMed]
 
Ng DK, Hui HN, Chan CH, et al. Obstructive sleep apnoea in children with Down syndrome. Singapore Med J. 2006;47(9):774-779. [PubMed]
 
Shott SR, Amin R, Chini B, Heubi C, Hotze S, Akers R. Obstructive sleep apnea: should all children with Down syndrome be tested? Arch Otolaryngol Head Neck Surg. 2006;132(4):432-436. [CrossRef] [PubMed]
 
Austeng ME, Øverland B, Kværner KJ, et al. Obstructive sleep apnea in younger school children with Down syndrome. Int J Pediatr Otorhinolaryngol. 2014;78(7):1026-1029. [CrossRef] [PubMed]
 
Shete MM, Stocks RMS, Sebelik ME, Schoumacher RA. Effects of adeno-tonsillectomy on polysomnography patterns in Down syndrome children with obstructive sleep apnea: a comparative study with children without Down syndrome. Int J Pediatr Otorhinolaryngol. 2010;74(3):241-244. [CrossRef] [PubMed]
 
Goldstein NA, Armfield DR, Kingsley LA, Borland LM, Allen GC, Post JC. Postoperative complications after tonsillectomy and adenoidectomy in children with Down syndrome. Arch Otolaryngol Head Neck Surg. 1998;124(2):171-176. [CrossRef] [PubMed]
 
de Moura CP, Andrade D, Cunha LM, et al. Down syndrome: otolaryngological effects of rapid maxillary expansion. J Laryngol Otol. 2008;122(12):1318-1324. [CrossRef] [PubMed]
 
Resta O, Barbaro MP, Giliberti T, et al. Sleep related breathing disorders in adults with Down syndrome. Downs Syndr Res Pract. 2003;8(3):115-119. [CrossRef] [PubMed]
 
Guimaraes CV, Donnelly LF, Shott SR, Amin RS, Kalra M. Relative rather than absolute macroglossia in patients with Down syndrome: implications for treatment of obstructive sleep apnea. Pediatr Radiol. 2008;38(10):1062-1067. [CrossRef] [PubMed]
 
Fricke BL, Donnelly LF, Shott SR, et al. Comparison of lingual tonsil size as depicted on MR imaging between children with obstructive sleep apnea despite previous tonsillectomy and adenoidectomy and normal controls. Pediatr Radiol. 2006;36(6):518-523. [CrossRef] [PubMed]
 
Bravo MNC, Kaul A, Rutter MJ, Elluru RG. Down syndrome and complete tracheal rings. J Pediatr. 2006;148(3):392-395. [CrossRef] [PubMed]
 
van Gameren-Oosterom HB, van Dommelen P, Schönbeck Y, Oudesluys AM, van Wouwe JP, Buitendijk SE. Prevalence of overweight in Dutch children with Down syndrome. Pediatrics. 2012;130(6):e1520-e1526. [CrossRef] [PubMed]
 
Melville CA, Cooper SA, McGrother CW, Thorp CF, Collacott R. Obesity in adults with Down syndrome: a case-control study. J Intellect Disabil Res. 2005;49(pt 2):125-133. [CrossRef] [PubMed]
 
Schwandt P. Defining central adiposity in terms of clinical practice in children and adolescents. Int J Prev Med. 2011;2(1):1-2. [PubMed]
 
Grunstein R, Wilcox I, Yang T-S, Gould Y, Hedner J. Snoring and sleep apnoea in men: association with central obesity and hypertension. Int J Obes Relat Metab Disord. 1993;17(9):533-540. [PubMed]
 
Rubin SS, Rimmer JH, Chicoine B, Braddock D, McGuire DE. Overweight prevalence in persons with Down syndrome. Ment Retard. 1998;36(3):175-181. [CrossRef] [PubMed]
 
Macchini F, Leva E, Torricelli M, Valadè A. Treating acid reflux disease in patients with Down syndrome: pharmacological and physiological approaches. Clin Exp Gastroenterol. 2011;4:19-22. [CrossRef] [PubMed]
 
May JG, Shah P, Lemonnier L, Bhatti G, Koscica J, Coticchia JM. Systematic review of endoscopic airway findings in children with gastroesophageal reflux disease. Ann Otol Rhinol Laryngol. 2011;120(2):116-122. [CrossRef] [PubMed]
 
Attal P, Chanson P. Endocrine aspects of obstructive sleep apnea. J Clin Endocrinol Metab. 2010;95(2):483-495. [CrossRef] [PubMed]
 
Lin CC, Tsan KW, Chen PJ. The relationship between sleep apnea syndrome and hypothyroidism. Chest. 1992;102(6):1663-1667. [CrossRef] [PubMed]
 
Devdhar M, Ousman YH, Burman KD. Hypothyroidism. Endocrinol Metab Clin North Am. 2007;36(3):595-615. [CrossRef] [PubMed]
 
Bull MJ; Committee on Genetics. Health supervision for children with Down syndrome. Pediatrics. 2011;128(2):393-406. [CrossRef] [PubMed]
 
Cua CL, Blankenship A, North AL, Hayes J, Nelin LD. Increased incidence of idiopathic persistent pulmonary hypertension in Down syndrome neonates. Pediatr Cardiol. 2007;28(4):250-254. [CrossRef] [PubMed]
 
Galambos C. Alveolar capillary dysplasia in a patient with Down’s syndrome. Pediatr Dev Pathol. 2006;9(3):254-255. [CrossRef] [PubMed]
 
Shehata BM, Abramowsky CR. Alveolar capillary dysplasia in an infant with trisomy 21. Pediatr Dev Pathol. 2005;8(6):696-700. [CrossRef] [PubMed]
 
Chi TL, Krovetz LJ. The pulmonary vascular bed in children with Down syndrome. J Pediatr. 1975;86(4):533-538. [CrossRef] [PubMed]
 
Loughlin GM, Wynne JW, Victorica BE. Sleep apnea as a possible cause of pulmonary hypertension in Down syndrome. J Pediatr. 1981;98(3):435-437. [CrossRef] [PubMed]
 
Levine OR, Simpser M. Alveolar hypoventilation and cor pulmonale associated with chronic airway obstruction in infants with Down syndrome. Clin Pediatr (Phila). 1982;21(1):25-29. [CrossRef] [PubMed]
 
Freezer NJ, Bucens IK, Robertson CF. Obstructive sleep apnoea presenting as failure to thrive in infancy. J Paediatr Child Health. 1995;31(3):172-175. [CrossRef] [PubMed]
 
Carskadon MA, Pueschel SM, Millman RP. Sleep-disordered breathing and behavior in three risk groups: preliminary findings from parental reports. Childs Nerv Syst. 1993;9(8):452-457. [CrossRef] [PubMed]
 
Rosen D. Management of obstructive sleep apnea associated with Down syndrome and other craniofacial dysmorphologies. Curr Opin Pulm Med. 2011;17(6):431-436. [PubMed]
 
Capone GT, Aidikoff JM, Taylor K, Rykiel N. Adolescents and young adults with Down syndrome presenting to a medical clinic with depression: co-morbid obstructive sleep apnea. Am J Med Genet A. 2013;161A(9):2188-2196. [CrossRef] [PubMed]
 
Edgin JO, Pennington BF, Mervis CB. Neuropsychological components of intellectual disability: the contributions of immediate, working, and associative memory. J Intellect Disabil Res. 2010;54(5):406-417. [CrossRef] [PubMed]
 
Fernandez F, Edgin JO. Poor sleep as a precursor to cognitive decline in Down syndrome: a hypothesis. J Alzheimers Dis Parkinsonism. 2013;3(2):124. [PubMed]
 
Rossor MN, Fox NC, Mummery CJ, Schott JM, Warren JD. The diagnosis of young-onset dementia. Lancet Neurol. 2010;9(8):793-806. [CrossRef] [PubMed]
 
Muchová J, Zitňanová I, Duračková Z. Oxidative stress and Down syndrome. Do antioxidants play a role in therapy? Physiol Res. 2014;63(5):535-542. [PubMed]
 
Lavie L. Obstructive sleep apnoea syndrome—an oxidative stress disorder. Sleep Med Rev. 2003;7(1):35-51. [CrossRef] [PubMed]
 
Gath A, Gumley D. Behaviour problems in retarded children with special reference to Down’s syndrome. Br J Psychiatry. 1986;149:156-161. [CrossRef] [PubMed]
 
Sedky K, Bennett DS, Carvalho KS. Attention deficit hyperactivity disorder and sleep disordered breathing in pediatric populations: a meta-analysis. Sleep Med Rev. 2014;18(4):349-356. [CrossRef] [PubMed]
 
Fitzgerald DA, Paul A, Richmond C. Severity of obstructive apnoea in children with Down syndrome who snore. Arch Dis Child. 2007;92(5):423-425. [CrossRef] [PubMed]
 
Ng DK, Chan CH, Cheung JM. Children with Down syndrome and OSA do not necessarily snore. Arch Dis Child. 2007;92(11):1047-1048. [PubMed]
 
Kuehni CE, Strippoli MP, Chauliac ES, Silverman M. Snoring in preschool children: prevalence, severity and risk factors. Eur Respir J. 2008;31(2):326-333. [CrossRef] [PubMed]
 
Kheirandish-Gozal L, Gozal D. Intranasal budesonide treatment for children with mild obstructive sleep apnea syndrome. Pediatrics. 2008;122(1):e149-e155. [CrossRef] [PubMed]
 
Goldbart AD, Goldman JL, Veling MC, Gozal D. Leukotriene modifier therapy for mild sleep-disordered breathing in children. Am J Respir Crit Care Med. 2005;172(3):364-370. [CrossRef] [PubMed]
 
Sato K, Shirakawa T, Niikuni N, Sakata H, Asanuma S. Effects of oral care in Down syndrome children with obstructive sleep apnea. J Oral Sci. 2010;52(1):145-147. [CrossRef] [PubMed]
 
Likar LL, Panciera TM, Erickson AD, Rounds S. Group education sessions and compliance with nasal CPAP therapy. Chest. 1997;111(5):1273-1277. [CrossRef] [PubMed]
 
Smith CE, Dauz ER, Clements F, et al. Telehealth services to improve nonadherence: a placebo-controlled study. Telemed J E Health. 2006;12(3):289-296. [CrossRef] [PubMed]
 
Waldman HB, Hasan FM, Perlman S. Down syndrome and sleep-disordered breathing: the dentist’s role. J Am Dent Assoc. 2009;140(3):307-312. [CrossRef] [PubMed]
 
Lim J, Lasserson TJ, Fleetham J, Wright J. Oral appliances for obstructive sleep apnoea. Cochrane Database Syst Rev. 2003;; (4):CD004435.
 
Merrell JA, Shott SR Sr. OSAS in Down syndrome: T&A versus T&A plus lateral pharyngoplasty. Int J Pediatr Otorhinolaryngol. 2007;71(8):1197-1203. [CrossRef] [PubMed]
 
Goldman JL, Baugh RF, Davies L, et al. Mortality and major morbidity after tonsillectomy: etiologic factors and strategies for prevention. Laryngoscope. 2013;123(10):2544-2553. [PubMed]
 
Roland PS, Rosenfeld RM, Brooks LJ, et al; American Academy of Otolaryngology—Head and Neck Surgery Foundation. Clinical practice guideline: polysomnography for sleep-disordered breathing prior to tonsillectomy in children. Otolaryngol Head Neck Surg. 2011;145(suppl 1):S1-S15. [CrossRef] [PubMed]
 
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