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Review
. 2021 Nov 1;321(5):L892-L899.
doi: 10.1152/ajplung.00434.2020. Epub 2021 Sep 1.

Lung disease manifestations in Down syndrome

Soula Danopoulos  1 , Gail H Deutsch  2 , Claire Dumortier  1 , Thomas J Mariani  3 , Denise Al Alam  1
Affiliations
Review

Lung disease manifestations in Down syndrome

Soula Danopoulos et al. Am J Physiol Lung Cell Mol Physiol. .

Abstract

Down syndrome (DS) is one of the most prevalent chromosomal abnormalities worldwide, affecting 1 in 700 live births. Although multiple organ systems are affected by the chromosomal defects, respiratory failure and lung disease are the leading causes of morbidity and mortality observed in DS. Manifestations of DS in the respiratory system encompass the entire lung starting from the nasopharynx to the trachea/upper airways to the lower airways and alveolar spaces, as well as vascular and lymphatic defects. Most of our knowledge on respiratory illness in persons with DS arises from pediatric studies; however, many of these disorders present early in infancy, supporting developmental mechanisms. In this review, we will focus on the different lung phenotypes in DS, as well as the genetic and molecular pathways that may be contributing to these complications during development.

Keywords: Down syndrome; development; lung.

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Conflict of interest statement

No conflicts of interest, financial or otherwise, are declared by the authors.

Figures

Figure 1.
Figure 1.
Cartoon summarizing the mechanisms underlying lung disease in Down syndrome. This cartoon is demonstrating an individual with Down syndrome. It is summarizing the possible upper airway, lower airway, alveolar space, and endothelial anomalies these individuals may experience. Furthermore, it is suggesting the possible mechanisms that may be contributing to these anomalies. For more information regarding the pathologies and the potential mechanisms, refer to Table 1 and the associated references. [Created with BioRender.com “Macro to Micro View of the Lungs” template and published with permission.]
Figure 2.
Figure 2.
Lung pathology in Down syndrome. A and B: subpleural cystic dilatation of alveolar spaces (arrows) are characteristic, visualized on both gross and microscopic examination of the lung. C: pulmonary hypoplasia in an 8-mo-old infant with congenital heart disease is visualized on lung biopsy by the markedly enlarged alveolar spaces, compare with alveolar spaces in B and size of the airways (*). D: a double-capillary network in the alveolar septa (arrowheads) of a term infant with trisomy 21 (left), compared with normal term alveolar septa (right). E: a 2.5-mo-old with complex congenital heart disease and severe pulmonary hypertension has occlusive wall thickening in a pulmonary artery (a). F: pulmonary hemosiderosis (brown pigment in alveolar macrophages) and acute hemorrhage in a 3-yr-old who presented with anemia.
See this image and copyright information in PMC

References

    1. Weijerman ME, van Furth AM, Vonk Noordegraaf A, van Wouwe JP, Broers CJ, Gemke RJ. Prevalence, neonatal characteristics, and first-year mortality of Down syndrome: a national study. J Pediatr 152: 15–19, 2008. doi:10.1016/j.jpeds.2007.09.045. - DOI - PubMed
    1. Colvin KL, Yeager ME. What people with Down Syndrome can teach us about cardiopulmonary disease. Eur Respir Rev 26: 160098, 2017. doi:10.1183/16000617.0098-2016. - DOI - PMC - PubMed
    1. Lyle R, Béna F, Gagos S, Gehrig C, Lopez G, Schinzel A, Lespinasse J, Bottani A, Dahoun S, Taine L, Doco-Fenzy M, Cornillet-Lefèbvre P, Pelet A, Lyonnet S, Toutain A, Colleaux L, Horst J, Kennerknecht I, Wakamatsu N, Descartes M, Franklin JC, Florentin-Arar L, Kitsiou S, Ait Yahya-Graison E, Costantine M, Sinet PM, Delabar JM, Antonarakis SE. Genotype–phenotype correlations in Down syndrome identified by array CGH in 30 cases of partial trisomy and partial monosomy chromosome 21. Eur J Hum Genet 17: 454–466, 2009. doi:10.1038/ejhg.2008.214. - DOI - PMC - PubMed
    1. Weijerman ME, van Furth AM, van der Mooren MD, van Weissenbruch MM, Rammeloo L, Broers CJ, Gemke RJ. Prevalence of congenital heart defects and persistent pulmonary hypertension of the neonate with Down syndrome. Eur J Pediatr 169: 1195–1199, 2010. doi:10.1007/s00431-010-1200-0. - DOI - PMC - PubMed
    1. Davidson MA. Primary care for children and adolescents with Down syndrome. Pediatr Clin North Am 55: 1099–1111, xi, 2008. doi:10.1016/j.pcl.2008.07.001. - DOI - PubMed

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