INTRODUCTION
Down syndrome (DS) was first characterized in 1866 by John Langdon Down, who described
“individuals with peculiar clinical manifestations”. Furthermore, in 1958, Jérôme
Lejeune and Pat Jacobs stated that DS is a genetic syndrome related to a trisomy of
chromosome 21. The DS prevalence in USA is around 13.56 for every 10,000 live births[1]–[3].
Clinical manifestations vary widely from person to person, but cognitive impairment
is commonly noted in this syndrome[4],[5]. Also, there are some common phenotypic features in individuals with DS, such as
muscle hypotonia, macroglossia, brachycephaly, epicanthal folds, flat nasal bridge,
micrognathia, low-set ears, excessive skin on the nape, single transverse palmar crease,
clinodactyly of the fifth finger, and a larger gap between the first and second toes[6],[7].
Sleep plays a critical role in good health and well-being. For this reason, sleep
disorders in children and adolescents are associated with problems in physical, behavioral,
and physiological development and pose an additional risk for obesity, endocrine disorders,
depression, immunological, and heart diseases[8]–[10]. These disorders are commonly observed in children with DS and can lead to significant
behavioral and cognitive morbidities in individuals with DS[11]–[13].
The aim of this study was to provide a systematic review to evaluate sleep disorders
in people with Down syndrome, focusing on clinical presentation, pathophysiology,
and treatment strategies.
METHODS
A systematic review of the literature, based on the PRISMA statement and the recommendations
for systematic review and meta-analysis, was conducted to investigate the main sleep
disorders in patients with Down syndrome and their treatment[13]. Search strategies were based on combinations of keywords “Down syndrome”, “trisomy
21”, “sleep disorders”, “dyssomnias”, “sleep apnea”, “obstructive”, “sleeplessness”,
“insomnia”, “parasomnias”, and “excessive daytime sleepiness”, which were defined
based on previous research in the Medical Subject Headings (MeSH) system. PubMed and
Science Direct were used as databases, with a publication period of January 2011 to
March 2021.
Researchers 1 and 2 (R.A.S and L.H.C) considered the topics covered in each article
searched, in addition to the inclusion and exclusion criteria. Treatment-only studies
were excluded; the focus was on studies that addressed sleep disorders in patients
with DS.
Inclusion criteria were: original studies and retrospective chart reviews written
in in English and with no restriction on health, age, or gender of subjects. Exclusion
criteria were: papers not related to sleep disorders in DS patients after reading
the full text and editorials, letters to the editor, review articles, case reports,
and meeting abstracts. The collected data were compiled into a spreadsheet containing
all relevant information from the studies, including authors, year of publication,
journal name, sample characteristics (size, gender, age, and geographic area), data
collection methods, clinical diagnosis, and assessed sleep disorder.
RESULTS
An initial search identified 3559 studies from the past 10 years. Subsequently, editorials,
letters to the editor, review articles, case reports, meeting abstracts, and laboratory-based
studies, including animal studies, were excluded, remaining 163 articles. After reading
full-text articles, that met all predefined criteria, and excluding duplicates, 52
articles were included in this systematic review ([Figure 1]).
Figure 1Flowchart of the literature search based on the recommendations of the Preferred Reporting
Items for Systematic Reviews and Meta-Analysis.
Among the selected studies were papers from 14 countries, most of them from the USA
and Belgium. Regarding the population studied, most studies included children and
adolescents under 18 years of age, and only 9 included the adult population. The main
results are summarized in [Tables 1] to [4]. Almost all studies were case series, and about 50% of the manuscripts used PSG
to define OSA.
Table 1
Synthesis of articles selected for systematic review on prevalence, etiology, correlating
factors, screening methods, and biomarkers for obstructive sleep apnea in Down syndrome
patients (age>18 years).
|
Author/year
|
Study
|
N° of patients
|
Mean age (years/months)
|
Time of follow up
|
Outcome
|
Conclusion
|
|
Carvalho et al., 2020[49]
|
Case series-Questionnaires; blood county
|
60 (DS)
|
>18 years
|
-
|
Adults with DS have a very high prevalence of OSA. Hematocrit levels, STOP-Bang questionnaires
(SBQ) showed a strong correlation with OSA severity. The SBQ performed well in identifying
moderate to severe OSA in this population.
|
Considered together, these results point to the need to perform OSA screening in all
adults with DS, and STOP-Bang may play a role in this screening.
|
|
Capone et al., 2013[38]
|
Case Control-PSG; Reiss and ABC scales
|
37 (9C) (28 DS)
|
19.8 (C) 21 (SD) years
|
5 years
|
–86% of DS cases had OSA compared with 44% of controls;
–Moderate-severe OSA was present in 54% of DS compared to 11% of controls;
–Intermittent sleep-associated hypoxia and REM sleep deficits were also more frequent
in DS. Across all subjects, prior tonsillectomy was not related to the presence or
absence of OSA.
|
The results of the study suggest that OSA is a common comorbidity in adolescents and
young people with DS and depression.
|
OSA: obstructive sleep apnea; DS: Down syndrome.
Table 2
Synthesis of articles selected for systematic review on prevalence, etiology, correlating
factors, screening methods, and biomarkers for obstructive sleep apnea in Down syndrome
patients (age<18 years).
|
Author/year
|
Study
|
N° of patients
|
Mean age (years/months)
|
Time of follow up
|
Outcome
|
Conclusion
|
|
Wijayaratne et al., 2021[48]
|
Case series-BMIZ score; sleep symptoms questionnaires
|
64 (DS)
|
3–19 years
|
-
|
Despite not being referred for clinical sleep assessment, 42% of children with DS
recruited from the community had moderate/severe OSA.
|
There were no differences in the quality-of-life behavior, daytime functioning, and
sleep symptom questionnaires although the clinical group had a higher body mass index
(BMI Z score) and overt signs of obesity. These results highlight the importance of
PSG screening in all children with DS.
|
|
Caloway et al., 2020[63]
|
Case series (Hypoglossal nerve stimulation-HGN)
|
20 (DS)
|
10-21 years
|
2 months
|
All 20 children were implanted with no long-term complications. We report two interval
adverse events, both of which were corrected with revision surgery. Twenty participants
completed the 2-month polysomnogram, with median percent reduction in titration AHI
of 85% (interquartile range=75–92%). The median nightly usage for these children was
9.21 hours/night. There was a median change in the OSA-18 score of 1.15, indicating
a moderate, yet significant, clinical change
|
HGN stimulation was safe and effective in the study population. Two minor surgical
complications were corrected surgically. Overall, these data suggest that pediatric
HGN stimulation appears to be a safe and effective therapy for children with DS and
refractory severe OSA.
|
|
Lee et al., 2020[18]
|
Case series-PSG and FSIQ
|
30 (DS)
|
11.3 years
|
-
|
The presence of OSA in children with DS was 80% in the 6 to 18 age group, with 62.5%
in the 6 to 12 age group; In individuals aged 6 and 12 years old, both OSA and% REM
were associated with lower scores on the WPPSI-R Vocabulary test;
|
OSA can be highly prevalent in children with DS in the community. Among children with
DS 6 and 12 years of age, OSA, and % REM were associated with their language function.
|
|
Waters et al., 2020[22]
|
Randomized Clinical TrialPSG
|
152 (DS)
|
5.0 (1st PSG) 8.2 (2nd PSG) years
|
3.5 years
|
In a tertiary sleep unit, a full spectrum of sleep-disordered breathing in Down syndrome
was seen from infancy onwards. Children having only 1 study were more likely to have
a normal or mild result than those having ≥2. Studies were more often severe in children
age <2 compared to those ≥2 years. After age 2 years, OSA severity increased with
age. Studies evaluating the effects of surgery (most often adenotonsillectomy) showed
resolution of disease to mild or normal in 53.3%.
|
Children having only one study were more likely to have normal results. Children with
multiple studies reflected disease surveillance, including follow-up after treatment
interventions.
|
|
Nerfeldt et al., 2020[21]
|
PSG before and after OSA surgical treatment
|
138 (DS)
|
6.1 years
|
-
|
The prevalence of OSA was 82.6 and 39.9% had severe OSA (AHI: 7.6); comorbidities
found were ear disease (60%), circulatory disease (51%) and endocrine disease (39%);
33 patients undergoing postoperative PSG had a residual prevalence of moderate or
severe OSA of 63.6%; Pre and postoperative PSG of patients with ATE and APP presented
median AHI changed from 21.1 to 12.4 and median OSA-18 from 54.0 to 35.0.
|
Uncertain surgical efficiency was indicated and no significant difference in results
for ATE and APP was demonstrated. The authors point out that the frequency of PSG
in the postoperative period was low and not systematic and that the groups were uneven
and small.
|
|
Anand et al., 2021[30]
|
PSG, Child Behavior Checklist (CBCL), developmental quotient (DQ)
|
53 (DS)
|
<18 years
|
-
|
Of 53 subjects (three to 11.8 years), 51 (96%) were found to have obstructive sleep
apnea (OSA). In both three to five year and six-to-12-year age groups, there was a
statistically significant positive correlation between the CBCL scores and the AHI
(rho=0.77 and 0.83, respectively). There was a statistically significant negative
correlation between the DQ and the AHI (rho=-0.62). In multiple linear regression,
AHI was the only independent variable that was associated with CBCL and DQ.
|
This study provides robust evidence that OSA can negatively influence the development
and behavior in children with Down syndrome as in typically developing children. Moreover,
with increasing severity of OSA, children with Down syndrome have more behavioral
abnormalities, especially attention deficit and hyperactivity, and also have poorer
development scores.
|
|
Chamseddin et al., 2019[45]
|
PSG
|
106 (DS)
|
2.0-18 years
|
6 years
|
90% of children had ≥1 medical comorbidities; 95 (90%) patients had OSA; and 46 (44%)
had severe OSA. Mean SaO2 nadir was lower among obese than in nonobese children (80 vs 85%). Obese versus nonobese
patients had a higher prevalence of severe OSA (56 vs 35%). The multivariable model
showed that severe OSA was associated only with weight.
|
Obese children with DS are at a high risk for severe OSA, with weight as the sole
risk factor. The results of this study show the importance of monitoring the weight
of children with DS and counseling parents of children with DS about weight loss
|
|
Howard et al., 2020[61]
|
PSG and oAHI
|
24 (DS)
|
<18 years
|
5 years
|
There was no significant change in oAHI, oxyhemoglobin saturation nadir, ETCO2, or percent TST in REM after treatment for any treatment group. There was no association
between reported symptoms and AHI severity or change in AHI.
|
In this cohort, the resolution of mild AOS was low for all treatment groups. These
findings are consistent with the current understanding that OSA in children with DS
is probably the result of multiple overlapping abnormalities contributing to the obstructive
pathology
|
|
|
|
|
|
OSA resolved in one patient treated with observation and two treated with medication,
but worsened in two each in the medication and observation groups. Resolution of OSA
occurred in 20% treated with medication, 7.7% with observation, and 0% with oxygen.
|
and suggests that a multimodal approach may be more appropriate in this population.
Prospective studies will be useful in the future to establish a better understanding
of treatment outcomes in children with DS and AOS lightweight.
|
|
Joyce et al., 2020[28]
|
Questionnaire Behavior rating inventory of executive functionpreschool version (BRIEF-P)
|
202 (DS)
|
36–71 months
|
-
|
OSA was associated with poorer working memory, emotional control and shifting.
|
Findings suggest that known executive function (EF) difficulties in DS are already
evident at this young age. Children with DS already have limited cognitive reserve
and cannot afford additional EF deficits associated with OSA. OSA is amenable to treatment
and should be actively treated in these children to promote optimal cognitive development.
|
|
von Lukowicz et al., 2019[58]
|
Polygraphy
|
18 (DS)
|
6.3 years
|
1.5 year
|
Eighteen recordings had ≥3 hours of artefact free recording in both the pretreatment
and posttreatment sleep study and were therefore included in the analysis. Mean age
was 6.3 years; 83% had OSA prior to intervention. Mean OAHI was 6.4 before and 6.4
after the intervention; the DI3 and SpO2nadir also did not change. Only the DI90 decreased
significantly from 2.7 to 2.1.
|
The 1-week intense myofunctional training camp evaluated here in children with DS
had only a marginal effect on OSA. Whether a longer follow-up period or duration of
intervention would yield stronger effects remains to be determined
|
|
Hill et al., 2018[50]
|
Case series-HPO
|
161 (DS)
|
0.5–6.0 years
|
-
|
In this training sample, the best HPO parameter predictors of OSA were the delta 12
s index >0.555 (sensitivity 92%, specificity 65%) and 3% oxyhemoglobin (SpO2) desaturation
index (3% ODI)>6.15 dips/hour (sensitivity 92%, specificity 63%). Combining variables
(delta 12 s index, 3% ODI, mean and minimum SpO2) achieved a sensitivity of 96% but reduced specificity to 52%.
|
HPO screening could halve the number of children with DS who require multichannel
sleep studies and reduce the burden on children, families, and health services alike.
This approach offers a practical universal screening approach for OSA in DS that is
accessible to non-specialist pediatricians.
|
|
Beppler et al., 2018[52]
|
Case series-pediBand (prototype)
|
-
|
5 years
|
-
|
The potential of pediBand in measuring physiological signals that can be used in the
diagnosis of OSA has been demonstrated.
|
It was demonstrated the potential of pediBand to successfully measure physiological
signals that can be used in the diagnosis of OSA.
|
|
Best et al., 2018[60]
|
Retrospective case series
|
65 (DS)
|
4.8
|
8.5 years
|
The mean AHI was 10.7 events/hour after AT. Twenty-three patients (35.4%) underwent
at least one additional surgical procedure after AT; 5 (7.7%) patients had ≥two additional
procedures. The most common additional surgical procedures were revision adenoidectomies
(n=8) and LT (n=13). Fifteen (23.1%) patients underwent at least one DISE to help
direct selection of surgical site/s.
|
This retrospective case series provided the foundation for an algorithm for management
of persistent OSA following primary AT in children with DS
|
|
Akkina et al., 2018[59]
|
PSG
|
24 (DS)
|
<18 years
|
3.5 years
|
The primary outcome was change in PSG parameters including AHI, OAHI, oxygen nadir,
oxygen desaturation index, and mean carbon dioxide level. While improvement was seen
in all PSG parameters, only improvement in oxygen nadir in children who had undergone
prior AT was statistically significant (88.5 to 90.9%, p=04).
|
This study confirms a high proportion of multisite airway obstruction in DS patients
with OSA. Although we observed an improvement across PSG measures, this study lacked
power to detect statistically significant changes. DISE directed surgery holds promise
as a beneficial tool for children with DS but a larger prospective study is needed
before specific recommendations may be made on incorporating DISE into the OSA diagnostic
and treatment algorithm for children with DS.
|
|
Slaats et al., 2018[65]
|
CT before the surgical procedure and PSG in the postoperative period
|
33 (DS)
|
4.3 years
|
3 years
|
Nineteen children underwent a second PSG after AT. Seventy-nine percent had persistent
OSA (OAHI> 2 events/h). A greater than 50% decrease in OAHI was observed in 79% and
these children had a significantly higher volume of the regions below the tonsils.
|
Children with severe OSA had a reduced air passage in the upper airway. Therefore,
this study suggests that an image of the upper airway may have an influence on the
choice of the text. This study is a pioneer in terms of analyzing the therapeutic
response with CT analysis of upper airway.
|
|
Nehme et al., 2017[43]
|
Case series-PSG and sleep questionnaires
|
119 (DS)
|
6.6 years
|
10 years
|
Sleep-disordered breathing (SDB) was present in 42.9% of children, with its highest
prevalence at age 8 years. Gastroesophageal reflux disease (GERD) was associated with
lower odds of OAHI>5 events/hour; Presence of difficulty breathing at night, reported
in the questionnaires of parents/caregivers, was significantly associated with apnea.
|
SDB is highly prevalent at all ages in children with Down syndrome. Symptoms did not
predict SDB in this population, although GERD may mimic SDB.
|
|
Skotko et al., 2017[51]
|
Case series-PSG, Questionnaire, image exam
|
102 (DS)
|
3.0–24.0 years
|
6 months
|
The main outcome measure was the AHI. Using a Logic Learning Machine (with a questionnaire,
imaging exam, and PSG) the best model had a cross-validated negative predictive value
of 73% for mild OSA and 90% for moderate or severe OSA; positive predictive values
were 55 and 25%, respectively.
|
In areas of the country where PSG is less available or affordable or when patients
with DS are unable or unwilling to tolerate a sleep study, the model might offer,
after validation, a viable alternative for providers looking to exclude moderate or
severe OSA with a questionnaire.
|
|
Dudoignon et al., 2017[55]
|
Retrospective cohort
|
57 (DS)
|
5.9–6.2 years
|
5.5 years
|
33% patients required noninvasive respiratory support. Mean age at noninvasive respiratory
support initiation was 7±7 years. On 11 patients with objective adherence data available,
mean compliance at 2±1 years of treatment was excellent with an average use per night
of 8hr46±3hr59 and 9 patient suing then on invasive respiratory support >4 hr/night.
Non-invasive respiratory support was associated with an improvement of nocturnal gas
exchange.
|
The study confirms the high prevalence and increased severity of OSA in children with
DS. Upper airway surgery represents a first line treatment but has a limited efficacy.
CPAP or NIV represent a very effective therapeutic option in case of persistent OSA
after upper airway surgery. The major problem of CPAP/NIV is compliance but good results
may be achieved by an experienced pediatric CPAP/NIV team.
|
|
Elsharkawi et al., 2017[53]
|
Urinary biomarkers
|
57 (DS)
|
4.0–9.1 years
|
-
|
Most night-sampled urinary biomarkers were elevated among individuals with DS relative
to matched HC. No urinary biomarker levels differed between individuals with DS with
vs. without OSA.
|
DS is associated with a different urinary biomarker profile when compared to HC. While
urinary biomarkers may be predictive of OSA in the general pediatric population, a
different approach is needed in interpreting urinary biomarker assays in individuals
with DS.
|
|
Prosser et al., 2017[57]
|
PSG
|
21 (DS)
|
4.3–9.3 years
|
10 years
|
The median improvement in overall AHI and the OAHI were 5.1 events/hour and 5.3 events/hour
(range, 22.9 to 41), respectively. The mean oxygen saturation nadir improved from
84 to 89%. The mean time with CO2>50 mmHg, central index, and percentage of rapid eye movement sleep were not significantly
different. After surgery, the OAHI was <5 events/hour in 61.9% and ≤1 in 19% of patients.
|
In children with DS, persistent OSA after AT and lingual tonsil hypertrophy, LT significantly
improved AHI, OAHI, and O2 saturation nadir. We recommend that children with DS should be evaluated for lingual
tonsil hypertrophy if found to have persistent OSA following T&A.
|
|
Jayaratne et al., 2017[54]
|
Stereophotography 3dMDface
|
63 (DS)
|
4.86–7.49 years
|
-
|
Participants with DS had maxillomandibular hypoplasia with smaller
|
Anthropometric analysis of different craniofacial landmarks
|
|
|
|
|
|
ear, nose, and eye measurements compared to neurotypically developing peers. We found
no statistically significant differences in 3D photogrammetric measurements between
participants with DS with or without OSA.
|
and measurements demonstrated that OSA cannot be correlated with the presence, absence,
or degree of any of these structural alterations within this population
|
|
Hill et al., 2016[17]
|
Case series-Polygraphy
|
188 (DS)
|
0.6–6 years
|
-
|
Moderate or severe OSA, defined by an OAHI>5/hour, was found in 14%; and mild-moderate
OSA (OAHI>1<5/h) in 59% of children. Male gender and habitual snoring predicted OSA
but did not have independent predictive power in the presence of the other factors.
Age in months, BMI, and tonsillar size did not predict OSA.
|
Moderate to severe OSA is common in very young children with DS. Examination of tonsillar
size did not predict OSA severity. Population-based screening for OSA is recommended
in these children and domiciliary cardiorespiratory polygraphy offers an acceptable
screening approach. Further research is needed to understand the natural history,
associated morbidity, optimal screening methodology, and treatment modality for OSA
in these children.
|
|
Maris et al., 2016[46]
|
Case series-PSG and questionnaire to parents/caregivers
|
122 (DS)
|
4–18 years
|
5 years
|
The overall prevalence of OSA was 66.4%.
|
A significant inverse correlation was found between age and AHI
|
|
Maris et al., 2016[37]
|
DISE e PSG
|
41 (DS)
|
4.2 years
|
5.5 years
|
Adeno-/tonsillar obstruction was found in 75.6% of the patients, and these patients
subsequently underwent UA surgery; A multilevel collapse was present in 85.4%. Tongue
base obstruction was present in ten patients (24.4%) and epiglottic collapse in 48.8%;
A significant improvement in oAHI from 11.4/h to 5.5/h was found, but persistent OSA
was present in 52% of the children.
|
Most patients with DS and OSA present with multilevel collapse on DISE. Adenotonsillectomy
results in a significant improvement of the oAHI; however more than half of the patients
had persistent OSA, probably due to multilevel collapse.
|
|
Maris et al., 2017[44]
|
PSG
|
34 (DS)
|
2.7–5.8 years
|
5.5 years
|
The majority presented with severe OSA (58.9%). AT was performed in 22 children, tonsillectomy
in 10 and adenoidectomy in two. Postoperatively, a significant improvement of the
OAHI was measured from 11.4/hour to 3.6/hour, with a parallel increase of the minimum
oxygen saturation. Children with initially more severe OSA had
|
AT results in a significant improvement of OSA in children with DS without a change
in sleep efficiency or sleep stage distribution. Severe OSA was associated with a
larger reduction of OSA severity.
|
|
|
|
|
|
significantly more improvement after UA surgery. Persistent OSA was found in 47.1%
of the children.
|
|
|
Brockmann et al.; 2016[14]
|
Case Control-HPSG
|
44 (DS)
|
3.6 years
|
-
|
83% of individuals obtained HPSG results comparable to PSG; 61% of the study subjects
had OSA, 18% of which were mild to moderate cases.
|
A portable polysomnographic home device may be helpful for diagnosing OSA in children
with DS.
|
|
Diercks et al., 2016[62]
|
Hypoglossal nerve stimulator (HGN) Case report
|
1 (DS)
|
14 years
|
6 months
|
Hypoglossal nerve stimulator therapy was well tolerated and effective, resulting in
significant improvement in the patient's OSA (overall AHI: 3.4 events/hour; AHI: 2.5–9.7
events/hour at optimal voltage settings depending on sleep stage and body position).
Five months after implantation, the patient's tracheotomy was successfully removed
and he continues to do well with nightly therapy.
|
The study demonstrated that the therapeutic measure obtained a well-tolerated and
effective result, significantly reducing the patient's respiratory impairment.
|
|
Ono et al., 2015[33]
|
Case series-Questionnaire
|
90 (DS)
|
16.6 years
|
-
|
71% of the sample suffered from snoring, 59% had excitation, 25% apnea, and 22% nocturia;
24% had an unusual sleep posture, with the majority being from 6 to 15 years old (52%);
Nocturia was the strongest predictor of unusual sleep positions for all OSA symptoms.
|
Symptoms related to OSA such as snoring and arousal are frequently observed in Japanese
people with DS. Anatomical factors might contribute to the pathogenesis of OSA in
people with DS, especially in the younger age groups. The high prevalence of unusual
sleep postures may indicate a need to protect or compensate for OSA in people with
DS who were less likely to be obese.
|
|
Brooks et al., 2015[26]
|
PSG, MSLT and neuropsychological tests
|
25 (DS)
|
7.2–18.7 years
|
1 year
|
The study demonstrated that the clinical findings were not predictive of the presence
of OSA (PSG identified OSA in 10 out of 25). The author presented that there was no
divergence in neuropsychological tests between children who had and did not have OSA.
|
Although SDB is common in children with DS, it is not a major contributor to their
cognitive deficits. Cognitive function is related to the amount of sleep and particularly
slow wave sleep. Successful treatment of SDB may improve their attention.
|
|
Thottam et al., 2015[39]
|
PSG in the pre and postoperative period of AT
|
36 (DS)
|
9.0 years
|
5.5 years
|
Children with DS who underwent surgery showed significant reductions in PSG obstructive
and central AHI; 86.7% of children with DS presented a significant reduction in AHI
for moderate or mild disease and 66.7% had resolution of central sleep apnea in the
postoperative period.
|
Children with DS who underwent AT demonstrated significant reductions in both obstructive
and central apneic indices on PSG. A significant number of patients with central sleep
apnea demonstrated resolution postoperatively.
|
|
Coverstone et al.; 2014[15]
|
PSG and McGill oximetry score
|
119 (DS)
|
7.0 years
|
3.5 years
|
OAHI was ≥2.5 for 50% of all individuals; 36.1% had McGill equal to 2 and 14.3% equal
to 3 or 4; McGill oximetry scores 3 and 4 are related to OSA and indicate clinical
follow-up.
|
McGill oximetry scores of 3 or 4 reliably identified patients with marked OSDB. The
possibility of central apneas causing hypoxemia must be considered in those with McGill
Score 2.
|
|
Lin et al., 2014[19]
|
Case series-PSG and McGill oximetry scale
|
49 (C) 49 (DS)
|
6.3 (C) 6.2 (DS) years
|
-
|
34.69% of children with DS presented OSA; OSA in children with DS was more severe
than in children in normal development; Children with DS had a higher mean of pCO2 during sleep and worse scores on McGill oximetry.
|
Children with DS have more complicated OSA and more impaired gas exchange compared
to children in the control group, with similar symptoms.
|
|
Breslin et al., 2014[27]
|
Case series-PSG and cognitive assessment
|
38 (DS)
|
9.7 years
|
3 months
|
Among children with DS, mean verbal IQ score was 9 points lower in those with comorbid
OSA (AHI>1.5) than in those without OSA, and performance on measures of cognitive
flexibility was poorer. Children with OSA showed increased light-stage sleep at the
expense of slow-wave sleep.
|
The results suggest that more work is needed to understand the influence of poor sleep
on learning in DS and other neurodevelopmental syndromes, many of which demonstrate
disordered sleep to some extent.
|
|
Stores et al., 2014[47]
|
Case series-Questionnaire, Oximetry
|
31 (DS)
|
2.3–16.7 years
|
-
|
No significant association was found between objective measures of restlessness during
sleep and ‘snoring’, nor were objective measures of restlessness related to reductions
in overnight blood oxygen levels. –The objective measure of snoring was significantly
associated with reductions in overnight blood oxygen levels.
|
The overnight measures used in the present study proved feasible and largely acceptable
to the children and their families. More time spent familiarizing children with the
procedure and the use of more recently developed recording systems would be likely
to improve the success rate with this particular procedure.
|
|
Austeng et al., 2014[40]
|
Case series-PSG
|
29 (DS)
|
8.0 years
|
-
|
AHI>1.5 in 28 of 29 children and an OAI>1 in 24 of 29 children. 19 children (66%)
had an AHI>5 and 17 children (59%) had an OAI>5 which indicated moderate to severe
OSA. No correlation was found between OSA and obesity or gender.
|
The high prevalence of disease found in these previously undiagnosed 8-year-old children
underlines the importance of performing OSA diagnostics in children with DS throughout
childhood. These findings suggest that the prevalence of OSA remains high up to early
school years.
|
OSA: obstructive sleep apnea; DS: Down syndrome.
Table 3
Synthesis of articles selected for systematic review about other sleep-related problems
in Down syndrome (other than obstructive sleep apnea); (age>18 years).
|
Author/year
|
Study
|
N° of patients
|
Mean of age (years/months)
|
Time of follow up
|
Outcome
|
Conclusion
|
|
Gomes et al., 2020[25]
|
Case series-maximum mouth opening-MMO; maximum bite force-MBF; maximum voluntary clench-MVC
|
35 (C) 35 (DS)
|
19–40 years
|
-
|
Electrical activities of the masseter and temporal muscles (at rest and in maximum
voluntary clench-MVC), maximum bite force-MBF, and maximum mouth opening-MMO were
investigated.
|
Masseter and temporal muscle hypotonia were found in all atypical subjects with DS.
This muscle dysfunction strongly was related to overweight/obesity, risks for development
of cardiovascular/metabolic diseases, OSA severity, successive snoring episodes, and
salivary flow reduction in DS.
|
OSA: obstructive sleep apnea; DS: Down syndrome.
Table 4
Synthesis of articles selected for systematic review about other sleep-related problems
in Down syndrome (other than obstructive sleep apnea); (age<18 years).
|
Author/Year
|
Study
|
N° of patients
|
Mean age (years/months)
|
Time of follow up
|
Outcome
|
Conclusion
|
|
Chawla et al., 2021[24]
|
Case series-CSHQ and sleep clinic
|
76 (DS)
|
-
|
-
|
The first study to report the prevalence of sleep problems in Australian children
with DS and to compare a community and referred group of children with DS directly.
|
This study reports a high prevalence of sleep problems in both a community and referred
group of Australian children with DS, and suggests that there are many children with
DS and sleep problems, particularly non-respiratory difficulties, who are potentially
not receiving adequate treatment.
|
|
Santoro et al., 2021[34]
|
PSG
|
82 (DS)
|
<18 years
|
-
|
Reported sleep positions were skewed towards lateral/decubitus (82.9%) compared to
prone (11.0%) and supine (6.1%). This was consistent with hypnogram data where 71%
of total sleep time in lateral/decubitus positions compared to prone (13%) and supine
(6%). Tonsillectomy was associated with lower obstructive AHI (OAHI) Sleep position
was not associated with age, gender, race, ethnicity, nor history of tonsillectomy.
Preferred sleep position was not correlated with OAHI or OSA severity.
|
This study highlights the possibility that children with DS may have preferential
sleep positions that cater to optimized airflow in the context of OSA, although further
prospective study is needed.
|
|
Shaw et al., 2021[29]
|
DSM 5 criteria and individual medical record numbers (MRN's) Chi-square test and Fisher's
exact AND Student's t-test
|
370 (DS)
|
2–17 years
|
1.5 year
|
Compared to typically developing children, children with DS may have more challenges
with adaptive functioning in the school setting (examples include complying with directions
and task persistence). Parents and teachers report higher rates of
|
Developmental/behavioral assessment is integral for detection of co-morbid conditions
among a pediatric DS population and prevention of diagnostic overshadowing.
|
|
|
|
|
|
non-compliance in children with DS compared to those without DS secondary to their
executive functioning and adaptive deficits
|
|
|
Bassam et al., 2021[31]
|
Heart rate (HR) and pulse transit time (PTT) (a surrogate inverse measure of BP change)
|
19 (DS) 19 (C)
|
3–18 years
|
-
|
Children with DS exhibited reduced nocturnal dipping of HR during total sleep. Fewer
children with DS exhibited a greater than 10% fall in HR between wake and REM sleep
compared to TD+children.
|
Findings demonstrate significantly reduced nocturnal dipping of HR in children with
DS compared to TD children matched for SDB severity, suggesting SDB has a greater
cardiovascular effect in these children. Further studies are required to fully understand
the mechanisms involved and to assess if treatment of SDB improves nocturnal dipping.
|
|
Siriwardhana et al., 2021[32]
|
PSG, nasal pressure, and transcutaneous carbon dioxide (TcCO2)
|
14 (DS) 14 (C)
|
3–19 years
|
2.5 years
|
Children with Down syndrome also had significantly lower average oxygen saturation
associated within each analysis window compared to typically developing children
|
Higher loop gain in children with Down syndrome and sleep disordered breathing indicates
that these children have more unstable ventilatory control, compared to age, gender
and sleep disordered breathing severity matched typically developing children. This
may be due to an inherent impairment in ventilatory control in children with Down
syndrome contributing to their increased risk of sleep disordered breathing, which
may inform alternative treatment options for this population.
|
|
Richard et al., 2020[42]
|
Case series-PSG and clinical files
|
28 (DS) 28 (C)
|
<18 years
|
5 years
|
Mean transcutaneous partial pressure of carbon dioxide (PtcCO2) during sleep was significantly
higher in patients with DS compared to controls.
|
This was the first study to compare nocturnal gas exchange in children with DS to
a control group of children with similar OSA, but not DS. Data demonstrated that children
with DS have increased transcutaneous partial pressure of carbon dioxide (PtcCO2) regardless of the presence of OSA and its severity. This may be due to respiratory
muscle hypotonia and/or ventilatory control alteration in patients with DS.
|
|
Giménez et al., 2018[16]
|
Case series-PSG, self-reports and, actigraphy.
|
35 (C) 47 (DS)
|
39.2 (C) 39.6(DS) years
|
-
|
Adults with DS had lower sleep efficiency, lower %REM, higher prevalence of OSA (78
versus 14%) and a higher AHI than patients in the control group. The DS group questionnaires
(PSQI and ESS) did not reflect the sleep disorders detected in the PSG.
|
Adults with DS have more sleep disorders, especially OSA. Sleep disorders were not
detected by self-reported sleep measures. Actigraphy, PSG and simplified devices validated
for OSA screening are important tools for diagnosis.
|
|
Maris et al., 2016[20]
|
Case series-CSHQ and PSG
|
54 (DS)
|
8.9 (C) 7.5 (DS) years
|
-
|
According to the CSHQ, 74.1% of children with DS had sleep problems.
|
Children with DS have a significantly higher prevalence of sleep problems, compared
to.
|
|
|
|
|
|
The general sleep problems were not related to age or gender, however, boys suffer
more from daytime sleepiness. Symptoms of respiratory sleep disorders are related
to parasomnias, longer sleep duration, and more daytime sleepiness.
|
normal developing healthy school-aged children. No correlations were found between
the relative reports on sleep problems and the underlying OSA or severity of OSA.
|
|
Ong et al., 2018[56]
|
Case series-Retrospective cohort database analysis
|
51292 (DS)
|
0–20
|
15 years
|
Tonsillectomy with adenoidectomy was the most common procedure in both groups, but
the proportion of tonsillectomy with adenoidectomy decreased over time. –The proportion
of palatal surgery and tracheostomy also decreased significantly, whereas there was
an increase in the proportion of lingual tonsillectomies, tongue-base reduction procedures,
and supraglossoplasty performed in both groups over time. The relative rates of change
in these procedures were higher in the DS population.
|
Tonsillectomy with adenoidectomy remains the most commonly performed procedure, although
there was a significant increase in other sleep surgeries performed (LT, tongue-base
reduction, and supraglossoplasty) between the two study periods, especially in children
with DS.
|
|
Mylavarapu et al., 2016[64]
|
Computational fluid dynamics, virtual surgery, CT and MRI
|
10 (DS)
|
5 years
|
-
|
There was a reduction, in 8 out of 10 patients, of AHI and the resistance of upper
airway, when compared to baseline values.
|
This study highlights the need for future studies, before using this technique in
surgical plans.
|
|
Hoffmire et al., 2014[23]
|
Case series-CSHQ and PSQ
|
107 (DS)
|
7–17 years
|
2 years
|
65% of children with DS had sleep problems in the CSHQ, but these problems were not
reported by their parents; In PSQ, 46% of children had sleep-related breathing problems
and 21% sleep-related movement disorders; Children with asthma, autism and a history
of enlarged adenoids and tonsils had more frequent sleep problems than children without
these comorbidities.
|
Sleep disorders are important but also under-recognized problems in children with
DS. It appears to be correlated with some prevalent comorbidities, which may provide
guidance to augment current practice guidelines to evaluate sleep problems in this
population.
|
|
Nisbet et al., 2014[36]
|
Case series-PSG and body posture record during sleep
|
76 (C) 76 (DS)
|
5.1 (C) 4.6 (DS) years
|
4.5 years
|
Sensor-recorded position (supine, prone, lateral) was expressed as the percentage
of total sleep time. The apnea-hypopnea index (AHI) was calculated in each sleep state
(NREM, REM), position, and position-sleep state combination. AHI was higher in REM
than NREM; nonetheless, the NREM AHI was higher in DS than NREM AHI that controls.
|
In DS and non-DS children alike, respiratory events are predominantly REM-related.
However, when matched for OSA severity, children with DS have a higher NREM AHI, which
is worse in the supine position, perhaps indicating a positional effect compounded
by underlying hypotonia inherent to DS.
|
|
|
|
|
|
The percentage of prone sleep was greater in DS than controls, but of supine or non-supine
sleep was not different between them.
|
|
|
Konstantinopoulou et al., 2016[41]
|
Case series-PSG, ECG and BPN
|
23 (DS)
|
2.7 months
|
-
|
At four months, there were no changes in cardiovascular outcomes or sleepiness between
those on actual versus sham CPAP. Hours of actual CPAP use were associated with improved
left ventricle function.
|
In children with DS, left ventricle diastolic function correlated with OSA severity,
which improved with the use of CPAP. There was a tendency towards increased sleepiness
in those with OSA, which correlated with the rate of awakening.
|
|
Senthilvel and Krishna, 2011[35]
|
PSG
|
17 (C) 17 (DS)
|
6 years
|
1.5 year
|
History of previous tonsillectomy (41%), congenital heart disease (of any type) (82%)
and hypothyroidism (41%) of SD compared to 24%, 12 and 0%, respectively of C. SD assumed
a unique body position sitting cross-legged flopped-forward with head resting on bed
while asleep.
|
Some DS children assume a peculiar body position, sitting cross-legged flopped-forward
with head resting on bed while asleep. This is absent in age and gender-matched controls
showing otherwise similar PSG characteristics. The reason for this posture is unclear
from this study.
|
OSA: obstructive sleep apnea; DS: Down syndrome.
DISCUSSION
Prevalence, etiology, and correlating factors for sleep disorders in individuals with
Down syndrome
The main sleep disorder associated with DS in the selected articles was obstructive
sleep apnea (OSA), with a prevalence ranging from 60 to 95%, depending on the criteria
used for diagnosis and the age of the patients. However, the heterogeneity between
the studies in terms of the method used for the diagnosis of the respiratory disorder
is noteworthy: polysomnography (PSG), home polysomnography (HPSG), home night sleep
records, cardiorespiratory polygraphy, housekeeping, McGill oximetry score, and actigraphy.
In some cases, only questionnaires or scales were used, such as: Pittsburgh Sleep
Quality Index (PSQI); Epworth Sleepiness Scale (ESS); Berlin Questionnaire (BQ); Child
Sleep Habits Questionnaire (CSHQ), which may have compromised the assessment of prevalence
[14]–[22].
We found few studies of parasomnia, insomnia, and daytime sleepiness in individuals
with DS. Two studies found that some sleep problems were significantly more common
in the population with DS, such as: resistance to bedtime, sleep duration, sleep anxiety,
night watch, parasomnias, and daytime sleepiness[20],[23],[24]. However, none of the studies addressed the presence of parasomnias and their most
frequent types isolated.
Maris et al. studied the occurrence of parasomnias, insomnia, and daytime sleepiness
by comparing two groups of DS patients, the first with younger individuals (4 to 6.9
years) and the second with older children (over 11 years). Parasomnia was reported
significantly less frequently with increasing age, which is also seen in normally
developed children. In children with DS, in contrast to children with normal development,
a decrease in the prevalence of sleep anxiety with increasing age was observed. Delay
in falling asleep occurred more frequently in children with DS than children with
normal development. Sleep onset delay in DS was significantly more common with increasing
age and in children with sleep anxiety. Daytime sleepiness occurred more frequently
among boys, regardless of age[20].
Gomes et al. examined the electrical activities of the masseter and temporal muscles
in patients with DS. These activities are atypical in these patients, indicating that
DS patients are at greater risk for overweight/obesity, cardiovascular/metabolic diseases,
OSA severity, and a salivary flow reduction [25].
Sleep disordered breathing in patients with Down syndrome and its negatives effects
on cognitive function
Several studies have been done associating sleep parameters and cognitive functions.
In one interesting study, neurophysiological parameters obtained in the PSG and multiple
sleep latency test (MSLT) were correlated with the answers in cognitive tests, and
found that shorter total sleep duration and greater sleepiness were associated with
poorer cognitive function in patients with DS. Furthermore, the lowest percentage
of slow-wave sleep was found to be a predictor of better adaptive behavior and academic
performance in individuals with DS. Another important finding was that appropriate
treatment of sleep-disordered breathing in DS patients resulted in better cognitive
performance, especially in the area of attention[26].
Lee et al. compared the results of PSG studies and cognitive scales assessing language,
behavior, and intellectual performance in patients with DS. They found that reduction
in the percentage of REM sleep and the presence of OSA were associated with impaired
language function in patients with DS[18]. Other studies with similar designs have correlated a reduction in slow-wave sleep
with poorer performance in verbal learning and executive functions in patients with
DS[26]–[30].
In addition, children with DS are at higher risk for sleep disordered breathing (SDB),
which can negatively affect the cardiovascular system. Besides, the risk of future
cardiovascular events is increased in these patients due to decreased nocturnal reduction
in heart rate (HR) and blood pressure (BP)[31].
Another study discussed the unstable ventilatory control that is more common in children
with DS. This finding indicates that these children are at greater risk for sleep
disordered breathing than patients without DS[32].
Sleep related movement disorders and unusual sleep postures in Down syndrome patients
Sleep problems in children with DS go beyond OSA and other sleep-disordered breathing.
Sleep-related movement disorders are also more common in individuals with DS[20],[23]. Hoffmire et al. observed that 21% of children with DS were positive for sleep-related
movement disorders measured with the CSHQ. Also, this risk was associated with asthma,
autism, and a history of enlarged adenoids and tonsils[23].
Other previous studies applied questionnaires and found that atypical positions such
as leaning forward with legs back, leaning forward with legs forward, leaning forward
with legs crossed, and sitting were common and were often related to the presence
of OSA diagnosis[33]. Additionally, patients with DS commonly present the unique position of sitting
with a flopped-forward body in which the head rests on the bed while asleep, which
contributes to optimized airflow[34]. The reason for this position is unclear, but authors conjectured that this may
be a protective mechanism for airway patency[35].
Another study used PSG and recording of body positions during sleep using sensors.
Subjects with DS spent a significantly longer duration of sleep in the prone position
and less in the right lateral decubitus position compared to subjects without the
paired syndrome by age and sex[36].
OBSTRUCTIVE SLEEP APNEA IS THE MOST PREVALENT SLEEP DISORDER IN PATIENTS WITH DS
As previously mentioned, OSA is the most prevalent sleep disorder in these patients,
and there are a few reasons for this. Maris et al. found that children with DS have
anatomical narrowing of the upper airway at different levels and are more prone to
collapse and thus at higher risk for OSA. Other factors contribute to explain the
association between OSA and DS such as muscle hypotonia, higher incidence of congenital
heart disease, hypothyroidism, lung disease, immunodeficiency, relative macroglossia
(due to smaller bone framework of mandible and maxilla)[37].
Some studies have included a control group of children and adolescents without DS
and found a prevalence of less than 20% of OSA, highlighting the important association
between DS and OSA[16],[21],[22],[38],[39]. Some authors claim that individuals with DS have more severe OSA and greater refractoriness
to treatment[16],[19],[39],[40].
According to studies by Konstantinopoulou et al., left ventricle diastolic function
correlates with the severity of OSA, which improves with the use of continuous positive
airway pressure (CPAP). In addition, they noted a tendency for increased sleepiness
in individuals with OSA, which was correlated with the awakening index. Further studies
are needed to confirm the findings described[41].
Coverstone et al. evaluated the probability of developing OSA in DS patients with
pulse oximetry and classified them according to the McGill score. Patients with McGill
score 3 or 4 (more than 3 desaturations below 80–85% in one night of sleep) or McGill
score 2 with increased body mass index (BMI>25 kg/m2) were referred by an otorhinolaryngologist due to their increased risk of adenotonsillar
hypertrophy. The authors suggest that patients with low McGill scores should be monitored
regularly by a specialist to obtain continuous assessment[15].
Nicolas et al. conducted the first study to compare nocturnal gas exchange in children
with DS with a control group of children with similar OSA. They concluded that patients
with DS have respiratory muscle hypotonia and/or an alteration in ventilatory control[42].
Nisbet's study showed that children with DS and OSA had a similar dominance of rapid
eye movements (REM) in breathing events compared to children with OSA and without
DS, but the children with DS had a higher NREM apnea-hypopnea index (AHI), even though
they were similar in terms of total AHI and had a similar percentage of sleep time
in NREM. Notably, children with DS in supine position had a higher NREM AHI than in
the non-supine position[36].
Obesity and other possible predictive variables for obstructive sleep apnea in patients
with Down syndrome
The association between obesity and the occurrence or severity of OSA in patients
with DS is controversial. Most studies included that no correlation exists between
higher BMI and OSA in this population[14],[17],[19],[33],[40],[43],[44], but it should be noted that most of these studies included children only.
On the other hand, Chamseddin et al. correlated obesity not only with a higher occurrence
of OSA in DS patients, but also with a high severity of OSA[45]. Similarly, two other studies reported that patients with DS, who had high BMI and/or
hypothyroidism, had greater upper airways narrowing and consequently a higher severity
of OSA. They also highlight the importance of preventing obesity in adolescence to
reduce the incidence of OSA in adults with the syndrome[15],[16]. Therefore, there is no consensus among researchers on the relationship between
OSA and overweight/obesity.
There are some predictive variables for the occurrence of OSA in patients with DS,
such as presence of parasomnias, longer total sleep time, daytime sleepiness, snoring,
witnessed apnea and nocturia[18],[23],[27],[33],[43],[46]. Hoffmire et al. described that the presence of asthma or allergic rhinitis is not
related to an increased risk of OSA in patients with DS[23]. In addition, there is no consensus among researchers on the association between
gastroesophageal reflux disease (GERD) and OSA in this population[23],[43]. Nehme et al. pointed out that the symptoms of GERD may be similar to those of OSA,
leading to a better performance of the PSG exam, which could contribute to a greater
identification of OSA in these patients[43].
Screening methods and biomarkers for obstructive sleep apnea in patients with Down
syndrome
Although PSG is considered the gold standard examination to define OSA, screening
methods have been investigated to evaluate sleep disorders in this population. Considering
the technical difficulties in performing PSG, the lack of availability of the exam,
and its high cost, alternatives must be sought. In this manuscript, it was shown that
only about 50% of selected studies used PSG to define OAS in DS patients. Although
the presence of restlessness and snoring are important indicators of OSA in patients
with DS, no significant association between these indicators and low oxygen saturation
was found in the Stores et al. study. Therefore, the authors suggest that the presence
of restlessness may be an important clinical feature to assess the need for a PSG[47],[48]. Questionnaires and clinical and laboratory data are used to identify moderate to
severe OSA in this population[49].
Another alternative is screening by home pulse oximetry (HPO), which could halve the
number of children with DS who need multichannel sleep studies[50]. Although these tests are useful, they cannot be used in isolation to diagnose breathing-related
sleep disorders[47],[50].
Two studies have used questionnaires as a tool for diagnosing OSA. In the first study,
conducted by Hoffmire et al., the CSHQ and the Pediatric Sleep Questionnaire (PSQ)
were applied[23]. In the second study, conducted by Maris et al., the CSHQ and the PSG were used
as auxiliary tools for diagnosis[20]. Both studies concluded that a large number of children with DS had sleep behavior
disorders (insomnia, parasomnias) and sleep-related breathing problems, but curiously,
their caregivers did not complain of such conditions. No relationship was found between
the scores obtained in the CSHQ and the OSA index[20],[23]. Therefore, the isolated use of questionnaires as a screening tool for OSA does
not seem to be an effective method.
In an interesting study conducted at Boston Children's Hospital, a predictive model
was created to help screen for OSA in patients with DS. The variables used were age,
sex, race, height, weight, BMI, sedentary behavior, blood pressure, peripheral O2 saturation, neck circumference, macroglossia assessment, Mallampatti classification,
Friedman/Brodksy scores, classification of scores, and current treatment for asthma,
GERD, or thyroid disease. Results of the following scales and questionnaires were
also used: PSQ, CSHQ, and Sleep Disorders Scale (SRBD), which were applied to parents
and/or guardians. Using a logic learning machine, the best model had a validated negative
predictive value of 73% for mild OSA and 90% for moderate or severe OSA. The final
model revealed that the most relevant variables (out of 101) were certain CSHQ questions,
SRBD questions, and the hypertension percentile. The study shows promising results
with models using clinical data and questionnaires and may be an interesting tool
for screening OSA in patients with DS[51].
Similarly, Beppler et al. have developed a prototype called PediBand to help diagnose
OSA in patients with DS. PediBand assesses the following physiological parameters:
heart rate and its variability, respiratory rate, and O2 saturation. This model is a promising tool to investigate sleep disordered breathing
in DS. However, as it is still a prototype, further clinical studies are needed to
strengthen the evidence for its use[52].
OSA biomarkers have also been studied in individuals with DS. Elsharkawi et al. measured
biomarkers such as epinephrine, norepinephrine, dopamine, serotonin, glycine, taurine,
γ-aminobutyric acid (GABA), glutamate, phenylethylamine (PEA), aspartic acid, histamine,
3,4-dihydroxyphenylacetic acid (DOPAC), 5 hydroxy acid (5-HIAA), tyramine, and tryptamine
in DS patients with OSA, DS patients without OSA, and in healthy controls, which were
equal in age and gender. The results showed that epinephrine, norepinephrine, dopamine,
and taurine were good predictors of the presence or absence of DS, but these results
were not statistically significant in distinguishing the presence or absence of OSA
in these patients. Thus, these urine biomarkers were ineffective tools for screening
OSA in individuals with DS[53]. It should also be noted that the low availability of the tests and the technical
difficulties in performing them are major obstacles to its use in clinical practice.
Jayaratne et al. conducted a 3D comparison of patients with and without OSA. An anthropometric
analysis scheme was developed to quantify facial norms with well-defined reference
points focusing on the soft tissues of the external morphology. Most anthropometric
measures were lower in individuals with DS, indicating maxillomandibular hypoplasia
and reduced measures of the nose, ears, and eyes. However, the authors compared patients
with DS and OSA versus patients with DS and without OSA and found no significant differences
in these measures. A limiting factor was the restriction to ethnicity (Caucasians
only), which requires a more in-depth analysis of different ethnicities and a wider
age range[54].
Treatment options for obstructive sleep apnea in patients with Down syndrome and new
perspectives
The main treatment options for OSA in DS patients are CPAP, surgery, and weight control.
Several therapeutic alternatives have been studied, considering that CPAP therapy
is not always available or tolerated, that surgical intervention is not always appropriate,
and that there is no consensus on whether there is a direct relationship between obesity
and OSA in patients with DS.
Several studies indicate that adenotonsillectomy (AT) is still the gold standard for
the treatment of OSA in patients with DS[37],[39],[44],[55]–[58]. Other possible interventions include lingual tonsillectomy (LT) and supraglossoplasty
(SGP). LT may be considered in the context of residual OSA after AT, despite its lower
efficacy[56]. The authors emphasize the importance of surgical planning with the identification
of upper airway obstruction sites and the main tool for this purpose is drug-induced
sleep endoscopy (DISE)[20],[59],[60].
Concerning drug treatment, further studies are needed to clarify its role in the OSA
in patients with DS. Intranasal corticosteroids may contribute to a local anti-inflammatory
effect by reducing apnea, but the effectiveness has not been fully demonstrated. A
retrospective study showed that children who underwent AT and used nasal corticosteroids
had less residual OSA than children who did not undergo this drug treatment. Considering
the small sample size of the study, the role of medication in the treatment of residual
OSA in DS remains uncertain[60],[61].
One of the new interventions that have been studied is myofunctional orofacial training
(MT). MT is based on the principle of strengthening orofacial and cervical functions
for muscular balance, thereby reducing the chances of recurrences due to the maintenance
of inadequate functional patterns[58]. Diercks et al., on the other hand, pioneered the investigation of a hypoglossal
nerve stimulation implant in the pediatric range as a prospect for treating a patient
with DS associated with severe OSA. The study demonstrated that the therapeutic intervention
produced a well-tolerated and effective outcome and significantly reduced the patient's
respiratory impairment[62],[63].
Three-dimensional reconstruction models from imaging exams — such as computer tomography
(CT) and magnetic resonance imaging (MRI) — look promising, but studies with a larger
sample of patients are needed to verify their real effectiveness[64],[65].
In conclusion, individuals with DS are at high risk of developing sleep-related breathing
disorders, mainly due to anatomical changes in the upper airway. The presence of sleep
disorders contributes to the deterioration of cognitive function in patients with
DS. PSG is the gold standard exam for determining OSA, but the high cost and difficulty
of technical approach are pushing for better options. OSA is the most studied sleep
disorder in patients with DS and its main treatment is AT. There are some emerging
perspectives on OSA treatment in patients with DS, but high-quality trials of multimodal
interventions are needed to provide robust evidence for the treatment of OSA in DS
individuals.
