Down Syndrome

Down syndrome, or trisomy 21, is a common genetic abnormality that occurs in nearly 1 in 700 births. Children born with Down syndrome (DS) have a distinct set of characteristics that have been attributed to the presence of an extra copy of an entire chromosome. Humans have 46 chromosomes (22 autosomal chromosome pairs, or disomies, and 1 pair of sex chromosomes: the X and Y’s we hear about with XX being female and XY being male). Occasionally, during the process of forming sperm or eggs (gametes, both with 23 unpaired chromosomes), a single chromosome remains paired. If this egg or sperm combines with the other parents gamete, the fertilized egg has an extra chromosome (now at 47 with a trisomy of whichever chromosome is extra). This can occur with several chromosomes, trisomy 21 is when there are three copies of chromosome 21. Additional information regarding trisomy 21 and the genetics explaining how Down syndrome occurs can be found at the National Down Syndrome Society’s webpage by clicking HERE.

It is important to recognize that infants and children with Down syndrome are, above all, infants and children. They eat, poop, sleep and cry just like any other infant and talk, walk, run and play just like any other child. But some children with Down syndrome have an increased chance of having additional challenges that warrant early screening or laboratory tests. The intent is not to point out flaws or disorders in these children, but to identify potential problems early before they become serious. Most pediatricians follow guidelines put together by expert pediatricians caring for children with Down syndrome and these guidelines are put in place to help identify challenges in their earliest stages so that they can be treated or reversed (American Academy of Pediatrics guidelines can be accessed HERE).

Respiratory Challenges in Children with Down Syndrome

One may note a lack of screening recommendations for respiratory conditions, however children with DS are at an increased risk for various conditions related to the lungs. While the scientific literature is not entirely clear about what percentage of children with DS will develop specific respiratory conditions, there are some reports that suggest an increased incidence. The percentages below are from a thorough review of the scientific literature but they aren’t perfect. They may either over- or under-estimate the incidence of each condition.

Abnormal Lung Development: Children with DS have been reported (in case series) to have abnormal lung development or pulmonary hypoplasia. This can often appear similar to bronchopulmonary dysplasia (BPD) when looking at lung tissue under the microscope. It’s not clear why this is the case, but recently scientists have suggested a link between genes on chromosome 21 that may impair blood vessel and lung development. Pulmonary hypoplasia can increase one’s chances of having low oxygen levels in the context of an infection. It can also increase the risk of developing pulmonary hypertension or high blood pressures of the blood vessels within the lungs. With growth in height and weight, it is likely that lungs continue to grow in children with DS probably decreasing such risks as time goes on.

Aspiration: Children with Down syndrome can have challenges with feeding for various reasons. These can include developmental, neurologic, behavioral or anatomic reasons. Lack of coordination of food in the mouth or a delayed transit of food from the mouth to the esophagus, both more common in children with DS, can increase the chances of food entering the airways. Delayed esophageal motility (movement of food down the esophagus) or reflux can also contribute to an increased risk of aspiration. In one study, aspiration occurred in nearly 40% of children with DS of which, 90% were doing so silently (meaning they didn’t cough, choke or sputter to suggest aspiration was happening). Aspiration can increase airway inflammation, increasing the incidence of infections including pneumonia. Additional information on aspiration can be found HERE.

Asthma: It isn’t clear whether or not an extra copy of chromosome 21 increases one’s risk for developing asthma. There are mixed reports of an increased incidence. None-the-less, asthma is a common challenge in the general population as a whole and should be something considered in any child who has a chronic cough, wheezing or exercise intolerance. For more information on asthma, click HERE.

Congenital Heart Disease: While technically not a lung problem, congenital heart disease (CHD) is a major risk factor for the development of pulmonary hypertension in children with DS. Approximately 50% of children with Down syndrome will have a CHD. A large portion of these will require surgical correction during infancy. For a more thorough discussion of congenital heart disease in children with Down syndrome, please click HERE.

Laryngomalacia: Laryngomalacia is a condition where the tissues around the area of the voice box (larynx) collapse down into the airway during a deep breath. This is typically not problematic, but does create an alarming sound (stridor) at times. Usually children with laryngomalacia grow out of it in time and rarely does it lead to difficulty breathing, poor feeding or poor weight gain. Additional information on laryngomalacia can be found HERE.

Obstructive Sleep Apnea: There are some sleep providers who believe nearly all children with Down syndrome have some degree of sleep disordered breathing, a majority of which is considered obstructive sleep apnea (OSA). Obstructive sleep apnea is a condition where there are airway obstructions that occur during particular phases of sleep. In children with DS, this often occurs due to relatively narrow upper airways (mid-face) with a tongue that is normal in size, but big relative to the smaller upper airways (nose and throat). Enlarged tonsils or adenoids, common culprits in OSA, can also lead to obstruction and difficulty breathing during sleep. At times, this can lead to low oxygen saturations. A good night’s sleep is really important, for many reasons, and OSA tends to disrupt a healthy nights sleep.

Pulmonary Hypertension: Children with DS have a higher incidence of pulmonary hypertension than the general population. There are multiple risk factors that may contribute to this, the most important being the presence of congenital heart disease (CHD). CHD often can lead to an increase in the amount of blood flowing to the lungs, which can, in time, lead to the development of high blood pressures in the lung circulation. There are other likely contributing factors including the reported abnormal lung development (with fewer blood vessels to receive the extra blood) and the increased incidence of disorders that can lead to low oxygen saturations (such as aspiration, recurrent pneumonia and obstructive sleep apnea). Low oxygen saturation leads to constriction of the blood vessels in the lungs and this can increase blood pressures within the lungs. Importantly, this can challenge the heart if left untreated. For more information on pulmonary hypertension, click HERE.

Recurrent Pneumonia: Children with DS are at risk for recurrent lower respiratory infections or pneumonia. While the reason for this isn’t entirely clear, there are probably several causes. Recurrent aspiration can increase the risk for developing respiratory tract infections in the lower airways, anatomic challenges (such as tracheomalacia, bronchomalacia, a tracheal bronchus or subglottic stenosis) can disrupt the ability to clear secretions and there is as yet a poorly defined immune abnormality in children with DS that likely increases their susceptibility to infections, particularly in the airways. For more information on recurrent pneumonia, click HERE.

Subglottic Stenosis: Subglottic stenosis is a narrowing of the airway just below the voice box (a region called the sub-glottis). While it’s not clear that this is a congenital (found at birth) or an acquired (something occurred to develop the issue such as needing a breathing tube for a prior surgery) condition, but it appears to be reported more frequently in children with DS.

Tracheomalacia: Tracheomalacia or bronchomalacia are defects in the structural support system for the airways (trachea = main airway in the neck; bronchi are subsequent airways within the lungs). Usually this manifests as a chronic or persistent cough, but can at times manifest as wheezing particularly in the context of a respiratory infection. Rarely does this lead to more challenging issues, but if severe can be a cause for recurrent pneumonia. Additional information on tracheomalacia can be found HERE.

When to look for respiratory challenges in children with DS

While there are limited recommendations for routine screening for respiratory challenges in children with DS, there are many subtle ways in which one’s pediatrician can pick up on respiratory disorders. Children with DS can be incredibly stoic and may not act sick, cough or complain about any symptoms. Parents and providers need to be aware of findings that might trigger a referral to a lung doctor (pulmonologist) or heart doctor (cardiologist). While turning blue (cyanosis) or a heart murmur appreciated on examination may signal a congenital heart disease, often prenatal ultrasounds or echocardiograms in the first day or two post-delivery identify structural heart defects early on. Respiratory symptoms may be less obvious and poor weight gain, weight loss, exercise or activity intolerance or difficulty feeding may be the presenting symptoms of a respiratory condition.

Not every child with Down syndrome needs to see a pulmonologist (lung doctor), however every child with DS should have a sleep study by the time they are 4 years old. A sleep study will assess for obstructive sleep apnea, which often has behavioral and neurologic consequences, but certainly increases the risk of developing pulmonary hypertension. In children with challenges feeding or growing, a swallow assessment is recommended, however this is not routine for all children with DS. In addition, annual complete blood cell count can sometimes help identify respiratory challenges as chronically low oxygen levels can lead to an increase in red blood cell production.

If your child has signs or symptoms of a respiratory condition, or you would like to be seen by a lung doctor (pulmonologist), just ask your pediatrician. We can also help connect you with a local pulmonologist or a Down syndrome specialist by contacting us HERE.

References:

1. McDowell KM, Craven DI. Pulmonary complications of Down syndrome during childhood. The Journal of pediatrics. 2011;158:319-25.

2. Maris M, Verhulst S, Wojciechowski M, Van de Heyning P, Boudewyns A. Prevalence of Obstructive Sleep Apnea in Children with Down Syndrome. Sleep. 2016;39:699-704.

3. Marcus CL, Keens TG, Bautista DB, von Pechmann WS, Ward SL. Obstructive sleep apnea in children with Down syndrome. Pediatrics. 1991;88:132-9.

4. Jackson A, Maybee J, Moran MK, Wolter-Warmerdam K, Hickey F. Clinical Characteristics of Dysphagia in Children with Down Syndrome. Dysphagia. 2016;31:663-71.

5. Bush D, Galambos C, Ivy DD, Abman SH, Wolter-Warmerdam K, Hickey F. Clinical Characteristics and Risk Factors for Developing Pulmonary Hypertension in Children with Down Syndrome. The Journal of pediatrics. 2018;202:212-9 e2.