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. 2024 May;63(4):474-481.
doi: 10.1177/00099228231179453. Epub 2023 Jun 12.

Cardiopulmonary Phenotypes and Protein Signatures in Children With Down Syndrome

Emily M DeBoer  1   2   3 , Kristine Wolter-Warmerdam  2 , Robin R Deterding  1   2 , Juana Marmolejo  2 , Tom Blumenthal  3 , Joaquin M Espinosa  3 , Francis Hickey  1   2 , Brandie D Wagner  1   2   4
Affiliations

Cardiopulmonary Phenotypes and Protein Signatures in Children With Down Syndrome

Emily M DeBoer et al. Clin Pediatr (Phila). 2024 May.

Abstract

Pulmonary disease, lower respiratory tract infection, and pneumonia are the largest causes of morbidity and mortality in individuals with Down syndrome (DS), but whether pulmonary diagnoses in children with DS are common and occur independently of cardiac disease and pulmonary hypertension (PH) is unknown. Cardiopulmonary phenotypes were examined in a cohort of 1248 children with DS. Aptamer-based proteomic analysis of blood was performed in a subset (n = 120) of these children. By the age of 10 years, half of the patients in this cohort (n = 634, 50.8%) had co-occurring pulmonary diagnoses. That proteins and related pathways were distinct between children with pulmonary diagnoses and those with cardiac disease and/or PH may indicate that pulmonary diagnoses appear to occur independently of cardiac disease and PH. Heparin sulfate-glycosaminoglycandegradation, nicotinate metabolism, and elastic fiber formation were ranked highest in the group with pulmonary diagnoses.

Keywords: Down syndrome; dysphagia; pneumonia; pulmonary hypertension; trisomy 21.

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Conflict of interest statement

Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Drs Deterding and DeBoer are founders and consultants for EvoEndoscopy and have patents in endoscopy procedures related to the company. Drs DeBoer and Deterding are consultants for Boehringer Ingelheim. Dr. DeBoer has received grant funding from the Cystic Fibrosis Foundation and NIH. Dr Deterding is founder and CEO of Now Vitals, Inc. and founder and Chief Medical Officer of Earables, Inc. The authors declare that they have no other conflict of interest.

Figures

Figure 1.
Figure 1.
Co-occurrence of cardiopulmonary phenotypes in Down syndrome. The full cohort of 1248 subjects was partitioned into cardiopulmonary phenotypes: P+ indicates the presence of a pulmonary morbidity (frequent pneumonia, chronic lung disease, aspiration, pleural effusion, chylothorax or other); C+ indicates the presence of a cardiac morbidity (ASD, AV canal, VSD, TOF, aberrant subclavian artery, coarctation, vascular ring defect or other); PH+ indicates the presence of pulmonary hypertension. The height of the bars corresponds to the proportion of full cohort that falls into each cardiopulmonary phenotype; the number of subjects in each phenotype is displayed on top of the bars. Abbreviations: ASD, atrial septal defect; AV, atrioventricular; VSD, ventricular septal defect; TOF, Tetralogy of Fallot; PH, pulmonary hypertension.
Figure 2.
Figure 2.
Heatmap of pathway ranks for each comparison. The top 10 ranked pathways (smallest P value) for pulmonary morbidity are distinct from PH and cardiac top-ranked pathways. Ranks are truncated at 50 to better illustrate the lower ranks. Abbreviations: PH, pulmonary hypertension; DS, Down syndrome; HS-GAG, heparin sulfate-glycosaminoglycan; mRNA, messenger RNA; NrCAM, Neuronal Cell Adhesion Molecule; ECM, Extracellular matrix; CS/DS chondroitin sulfate/dermatan sulfate; TPBS, temtamy preaxial brachydactyly syndrome; SEDCJD, spondyloepiphyseal dysplasia with joint dislocations; EDS, Ehlers-Danlos syndrome; JDSSDHD, joint dislocations, short stature, craniofacial dysmorphism, and cogenital heart defects.
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References

    1. Freeman SB, Taft LF, Dooley KJ, et al. Population-based study of congenital heart defects in Down syndrome. Am J Med Genet. 1998;80:213–217. - PubMed
    1. Bittles AH, Bower C, Hussain R, Glasson EJ. The four ages of Down syndrome. Eur J Public Health. 2007;17(2):221–225. - PubMed
    1. Fudge JC Jr, Li S, Jaggers J, et al. Congenital heart surgery outcomes in Down syndrome: analysis of a national clinical database. Pediatrics. 2010;126(2):315–322. - PMC - PubMed
    1. Evans JM, Dharmar M, Meierhenry E, Marcin JP, Raff GW. Association between Down syndrome and in-hospital death among children undergoing surgery for congenital heart disease: a US population-based study. Circ Cardiovasc Qual Outcomes. 2014;7(3):445–452. - PubMed
    1. Yang Q, Rasmussen SA, Friedman JM. Mortality associated with Down’s syndrome in the USA from 1983 to 1997: a population-based study. Lancet. 2002;359:1019–1025. - PubMed