Altered peripheral blood leukocyte subpopulations, function, and gene expression in children with Down syndrome: implications for respiratory tract infection.

OBJECTIVES: We tested the hypothesis that aberrant expression of Hsa21-encoded interferon genes in peripheral blood immune cells would correlate to immune cell dysfunction in children with Down syndrome (DS). STUDY DESIGN: We performed flow cytometry to quantify peripheral blood leukocyte subtypes and measured their ability to migrate and phagocytose. In matched samples, we measured gene expression levels for constituents of interferon signaling pathways. We screened 49 children, of which 29 were individuals with DS. RESULTS: We show that the percentages of two peripheral blood myeloid cell subtypes (alternatively-activated macrophages and low-density granulocytes) in children with DS differed significantly from typical children, children with DS circulate a very different pattern of cytokines vs. typical individuals, and higher expression levels of type III interferon receptor Interleukin-10Rb in individuals with DS correlated with reduced migratory and phagocytic capacity of macrophages. CONCLUSIONS: Increased susceptibility to severe and chronic infection in children with DS may result from inappropriate numbers and subtypes of immune cells that are phenotypically and functionally altered due to trisomy 21 associated interferonopathy.

Cardiopulmonary Phenotypes and Protein Signatures in Children With Down Syndrome.

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.

IGF1 deficiency integrates stunted growth and neurodegeneration in Down syndrome.

Down syndrome (DS), the genetic condition caused by trisomy 21 (T21), is characterized by stunted growth, cognitive impairment, and increased risk of diverse neurological conditions. Although signs of lifelong neurodegeneration are well documented in DS, the mechanisms underlying this phenotype await elucidation. Here we report a multi-omics analysis of neurodegeneration and neuroinflammation biomarkers, plasma proteomics, and immune profiling in a diverse cohort of more than 400 research participants. We identified depletion of insulin growth factor 1 (IGF1), a master regulator of growth and brain development, as the top biosignature associated with neurodegeneration in DS. Individuals with T21 display chronic IGF1 deficiency downstream of growth hormone production, associated with a specific inflammatory profile involving elevated tumor necrosis factor alpha (TNF-α). Shorter children with DS show stronger IGF1 deficiency, elevated biomarkers of neurodegeneration, and increased prevalence of autism and other conditions. These results point to disruption of IGF1 signaling as a potential contributor to stunted growth and neurodegeneration in DS.

Blood counts in children with Down syndrome.

BACKGROUND: Children with Down syndrome (DS) are more likely to have hematologic and immunologic abnormalities compared to their typically developing peers, but normal ranges have not been defined. The goal of this study was to create references for complete blood counts (CBCs) in patients with DS. METHODS: A retrospective investigation of 355 (male = 196, 55.2%; mean age = 6.49 years, SD = 5.07) healthy pediatric patients with DS who received a CBC between 2011 and 2017 as part of their medical care at a single, large, pediatric teaching hospital. Control data on 770 healthy patients without DS were included. Descriptive statistics were performed on demographic and clinical characteristics. Kruskal-Wallis H tests, nested analysis-of-variance tests, and t-tests were run to determine the significant associations. RESULTS: Age-related normative curves for healthy children with DS outlining 2.5th, 25th, 50th, 75th, and 97.5th percentiles are provided for total white blood count, hemoglobin concentration, hematocrit, mean corpuscular volume, and platelet, absolute neutrophil, absolute lymphocyte, eosinophil, monocyte, and basophil counts. Statistical differences were found between children with and without DS receiving care at the same hospital based on matched age/sex groups. CONCLUSIONS: This study demonstrates that patients with DS have different reference ranges for multiple blood counts compared to those without DS, creating a new resource for pediatricians to refer to when evaluating CBCs in this population.

Biomarkers of Pulmonary Hypertension Are Altered in Children with Down Syndrome and Pulmonary Hypertension.

OBJECTIVE: To evaluate the performance of pulmonary hypertension (PH) biomarkers in children with Down syndrome, an independent risk factor for PH, in whom biomarker performance may differ compared with other populations. STUDY DESIGN: Serum endostatin, interleukin (IL)-1 receptor 1 (ST2), galectin-3, N-terminal pro hormone B-natriuretic peptide (NT-proBNP), IL-6, and hepatoma-derived growth factor (HDGF) were measured in subjects with Down syndrome and PH (n = 29), subjects with Down syndrome and resolved PH (n = 13), subjects with Down syndrome without PH (n = 49), and subjects without Down syndrome with World Symposium on Pulmonary Hypertension group I pulmonary arterial hypertension (no Down syndrome PH group; n = 173). Each biomarker was assessed to discriminate PH in Down syndrome. A classification tree was created to distinguish PH from resolved PH and no PH in children with Down syndrome. RESULTS: Endostatin, galectin-3, HDGF, and ST2 were elevated in subjects with Down syndrome regardless of PH status. Not all markers differed between subjects with Down syndrome and PH and subjects with Down syndrome and resolved PH. NT-proBNP and IL-6 levels were similar in the Down syndrome with PH group and the no Down syndrome PH group. A classification tree identified NT-proBNP and galectin-3 as the best markers for sequentially distinguishing PH, resolved PH, and no PH in subjects with Down syndrome. CONCLUSIONS: Proteomic markers are used to improve the diagnosis and prognosis of PH but, as demonstrated here, can be altered in genetically unique populations such as individuals with Down syndrome. This further suggests that clinical biomarkers should be evaluated in unique groups with the development of population-specific nomograms.

Airwave oscillometry to measure lung function in children with Down syndrome.

BACKGROUND: Children with Down syndrome are at risk for significant pulmonary co-morbidities, including recurrent respiratory infections, dysphagia, obstructive sleep apnea, and pulmonary vascular disease. Because the gold standard metric of lung function, spirometry, may not be feasible in children with intellectual disabilities, we sought to assess the feasibility of both airwave oscillometry and spirometry in children with Down syndrome. METHODS: Thirty-four children with Down syndrome aged 5-17 years were recruited. Participants performed airwave oscillometry and spirometry before and 10 min after albuterol. Outcomes include success rates, airway resistance and reactance pre- and post-bronchodilator, and bronchodilator response. RESULTS: Participants were median age 9.2 years (interquartile range 7.2, 12.0) and 47% male. Airwave oscillometry was successful in 26 participants (76.5%) and 4 (11.8%) were successful with spirometry. No abnormalities in airway resistance were detected, and 16/26 (61.5%) had decreased reactance. A positive bronchodilator response by oscillometry was observed in 5/23 (21.7%) of those with successful pre- and post-bronchodilator testing. CONCLUSIONS: Measures of pulmonary function were successfully obtained using airwave oscillometry in children with Down syndrome, which supports its use in this high-risk population. IMPACT: Children with Down syndrome are at risk for significant pulmonary co-morbidities, but the gold standard metric of lung function, spirometry, may not be feasible in children with intellectual disabilities. This may limit the population's enrollment in clinical trials and in standardized clinical care. In this prospective study of lung function in children with Down syndrome, airwave oscillometry was successful in 76% of participants but spirometry was successful in only 12%. This study reinforces that measures of pulmonary function can be obtained successfully using airwave oscillometry in children with Down syndrome, which supports its use in this high-risk population.

Reach Out and Read Implementation in a Pediatric Down Syndrome Clinic.

INTRODUCTION: To examine the first Reach Out and Read (ROR) program in a pediatric Down syndrome (DS) clinic in the United States and the literacy behaviors of young children with DS and their families. METHOD: This is a large cohort (n = 747) review of children with DS participating in ROR and a family literacy survey (n = 209). Data from the electronic medical records were included. RESULT: On average, children with DS began independently reading at 6.15 years (standard deviation = 1.42). Overall, 36.7% of children with visual/audio impairments required additional encouragement. Time spent reading was impacted by the mother's education level. Differences were found among ROR participants with DS for reported favorite activity. DISCUSSION: ROR is an important clinic-based literacy program for children with DS. Children with DS attain independent reading abilities similar to typically developing peers when provided appropriate resources. Additional support is needed to encourage reading enjoyment in this population.

Child feeding practices in children with Down syndrome in relationship to ethnicity and BMI.

Children with Down syndrome (DS) exhibit higher overweight and obesity rates than their typically developing peers, although it is unknown whether parent feeding practices for children with DS are associated with child weight status or parental and demographic factors, especially in the Hispanic and Latino populations. A prospective study of 68 children with DS from 2 to 7 years of age, who received care at a single, large, pediatric academic hospital was conducted to evaluate parent child feeding practices. Parents completed the Child Feeding Questionnaire+ (CFQ+) assessing seven primary factors of feeding practices and comparisons to children without DS were conducted. Data for body mass index (BMI) and BMI-for-sex/age z score (BMIz scores) were collected in clinic at the time of CFQ+ completion for both parent and child. Parents of children with DS endorsed higher perceived responsibility but lower concern about child weight and restriction compared to previously reported feeding practices in typically developing children. Hispanic/Latino parents of children with DS reported higher perceived responsibility and monitoring than non-Hispanic/Latino parents of children with DS. Higher BMIz scores in children with DS correlated with greater perceived child weight (p = 0.001) and concern about child weight (p = 0.008). Differences in BMIz scores were observed when comparing sex/ethnicity groups as determined by one-way ANOVA (F(3,64) = 4.170, p = 0.009); with Hispanic/Latino boys with DS more likely to have obesity. Our results suggest a need for specific DS Guidelines to educate providers and parents of children with DS on recommended feeding practices prior to parental concern about their child's weight, especially in the Hispanic/Latino population.

Airway obstruction and inflammation on combined bronchoscopy in children with Down syndrome.

OBJECTIVE: To characterize the upper and lower airway findings in children with Down syndrome and chronic respiratory symptoms, based on evaluation by flexible bronchoscopy (FB) with bronchoalveolar lavage and microlaryngoscopy with bronchoscopy (MLB). STUDY DESIGN: A retrospective review was conducted of children with Down syndrome aged 1 month to 17 years, who underwent both FB and MLB within a 1-year timeframe between 2010 and 2019 at Children's Hospital Colorado. Anatomic airway findings are reported as frequencies within the cohort. Bronchoalveolar lavage fluid (BALF) culture results, cell differential, and cytopathology are reported as frequencies or mean ± standard deviation. BALF results were compared between children with and without dysphagia documented on a recent swallow evaluation. RESULTS: Overall, 168 children with Down syndrome were included, with median age of 2.1 years (interquartile range: 0.9-5.1 years). At least one abnormal airway finding was recorded in 96% of patients and 46% had at least three abnormal findings. The most common findings included tracheomalacia (39% FB; 37% MLB), subglottic stenosis (35% MLB), pharyngomalacia (32% FB), and laryngomalacia (16% FB; 30% MLB). Comparison of BALF based on dysphagia status showed that children with dysphagia had more frequent cultures positive for mixed upper respiratory flora (76% vs. 47%, p = 0.004) and a higher percentage of neutrophils (20% vs. 7%, p = 0.006). CONCLUSION: Abnormal findings for FB and MLB are common in children with Down syndrome and chronic respiratory symptoms, and performing the procedures together may increase the diagnostic yield.

Validation of the Childhood Dysphagia Management Scale (CDMS): An Impact Scale for determining medical home for dysphagia.

BACKGROUND: The results and recommendations from instrumental assessments of swallowing do not, by themselves, provide guidance regarding the type of medical management that might be needed for the pediatric patient with dysphagia. The aim of this study is to evaluate the reliability and validity of the Childhood Dysphagia Management Scale (CDMS), a clinical scale developed to estimate the impact of dysphagia and determine the need for a multidisciplinary medical home to manage dysphagia. METHODS: This was a prospective observational study implemented in three phases to evaluate validity and reliability of the CDMS. Analyses for internal consistency, inter-rater and intra-rater reliability, repeated measure, content, structural, criterion and external validity and hypothesis testing were conducted. RESULTS: This study established content, structural, internal, external, and criterion validity of the CDMS. The CDMS was found to have robust inter-rater (κ = 0.776) and intra-rater reliability (κ = 0.853), and consistency across repeated measures (κ = 0.853). Providers who used the CDMS had a high level of agreement with the recommended medical management plan. CDMS scores correlated (F(5,118) = 22.105, p < 0.001) with Functional Oral Intake Scale (FOIS) scores confirming that patients with significant diet restrictions were more likely to be referred for multidisciplinary care. To establish external validity, the CDMS was administered to a higher risk group, patients with Down syndrome, who were more likely to be referred for multidisciplinary care based on CDMS results versus the general swallowing disorders clinic population (F(1,281) = 24.357, p < 0.001). CONCLUSION: The CDMS is a reliable and valid scale for guiding decision-making regarding the medical home for pediatric dysphagia management.

Evaluation of 2011 AAP cervical spine screening guidelines for children with Down Syndrome.

PURPOSE: Atlantoaxial instability (AAI) has a higher incidence rate among individuals with Down syndrome (DS) than the non-DS population. In 2011, the American Academy of Pediatrics (AAP) updated its AAI screening guidelines for children with DS from radiographic screening to radiographs only if there are clinical symptoms suggestive of cervical spine pathology. An assessment of whether this alteration has been associated with an increase in AAI-associated spinal cord injury has not been undertaken. METHODS: We provide the first neurosurgical review of a large experience implementing the 2011 AAP guidelines. We reviewed the courses of patients with DS seen at the Sie Center for Down Syndrome at Children's Hospital Colorado who were evaluated for cervical spine disease and determined whether screening radiographic imaging could have led to earlier diagnosis or prevented development of neurological deficits. We also report an illustrative case of a 5-year-old female with Down syndrome who presented with instability after normal screening radiographs per the pre-2011 guidelines. RESULTS: The clinical experience of the Sie Center demonstrates that even when limiting imaging to patients who show signs or symptoms of spine pathology, the vast majority of x-rays are negative. Our exemplary patient presented to the emergency department for neck pain without a history of significant trauma. She was diagnosed and treated for atlantoaxial subluxation associated with os odontoideum. CONCLUSION: Routine radiographic screening may not be sufficiently predictive of DS individuals at risk to develop AAI. This experience supports the appositeness of the de-escalation of care asserted by the guidelines.

Keratoconus and corneal morphology in patients with Down syndrome at a pediatric hospital.

PURPOSE: To evaluate patients with Down syndrome for keratoconus and corneal abnormalities using Scheimpflug imaging (Pentacam HR) in a pediatric setting. METHODS: The Pentacam scans of patients with Down syndrome seen at Children's Hospital Colorado Ophthalmology Department were reviewed retrospectively, and the following data were collected: keratometry values, pachymetry values, components of the Belin ABCD Grading System, the Belin/Ambrosio enhanced ectasia display D value, and topometric indices, including ISV, IVA, and KI. Subjective interpretation was used to classify scans as normal, abnormal, keratoconus suspect, and definite keratoconus. RESULTS: A total of 56 eyes of 31 patients aged 4-24 years (mean, 12.4) were included. The average value for K1 was 44.95 ± 1.73 D (range, 40.90-49.3 D); for K2, 46.87 ± 2.16 D (range, 42.50-51.80 D); for Kmax, 48.20 ± 3.11 D (range, 43-61.7 D); and for Kmean, 45.81 ± 1.85 D (range, 41.7-50.35 D). Mean pachymetry at the thinnest point was 509 ± 44.24 µm (range, 410-612 µm) and at the apex was 519 ± 44.24 µm (range, 412-646 µm). The mean D value was 2.08 ± 1.57 (range, 0.08-9.71). There were 10 patients (32%) with either keratoconus suspect or definite keratoconus in at least one eye. CONCLUSIONS: We found a high frequency of keratoconus and keratoconus suspect in pediatric and young adult patients with Down syndrome. The corneas in this population had steeper K values and thinner pachymetry values compared to previously reported controls.

Associations between age, respiratory comorbidities, and dysphagia in infants with down syndrome.

OBJECTIVES: Children with Down syndrome (DS) have a high risk of dysphagia and the pediatric pulmonologist may be involved in diagnosis and management. The objective of this study is to evaluate the associations between age, dysphagia, and medical comorbidities in young children with DS. We hypothesized that swallow study findings are more likely to change in younger infants and that medical comorbidities may be associated with dysphagia. STUDY DESIGN: Results of videofluoroscopic swallow studies (VFSS) and fiberoptic endoscopic evaluation of swallowing (FEES) from 2010 to 2016 were collected retrospectively in children with DS with initial swallow study at less than 12 months of age. Results were analyzed for findings and change based on age at initial study, reason for referral, and medical comorbidities. RESULTS: One hundred eleven infants with 247 VFSS and 14 FEES were included. Deep laryngeal penetration and/or aspiration were found in 31.9% of infants less than 6 months and 51.3% of infants 6 to 12 months. Children with initial swallow study performed at greater than or equal to 6 months of age were more likely (80.0%) to have unchanged findings on follow-up study compared to children imaged at less than 6 months (35.3%). Laryngomalacia, pulmonary hypertension, pneumonia, and congenital cardiac disease were associated with dysphagia. CONCLUSION: We confirmed that dysphagia is common in infants with DS and comorbidities and provided preliminary evidence that swallow study findings may be more likely to change in children tested under 6 months of age. Providers should consider that results for instrumental swallow studies may change, particularly if the test was completed on a young infant.

Does Tonsillectomy Increase Obesity Risk in Children with Down Syndrome?

OBJECTIVES: To examine weight changes relative to surgical success in children with Down syndrome and obstructive sleep apnea (OSA). STUDY DESIGN: Retrospective chart review of children with Down syndrome undergoing tonsillectomy from 2005 to 2016 for OSA at a tertiary care children's hospital. Only patients with pre-and postoperative polysomnogram within 6 months of tonsillectomy were included. Demographics, weight, height, and polysomnogram data were collected. Body mass index (BMI), expressed as a percentage of the 95th percentile (%BMIp95), was calculated for 24 months prior to and following surgery. Pre-and postoperative OSA severity were also recorded. The postoperative obstructive/hypopnea index identified subjects with resolution of obstruction (obstructive/hypopnea index <2 events/hour) or persistent mild/moderate/severe obstructive apnea. Regression analyses were used to compare %BMIp95 pre- and post-tonsillectomy with %BMIp95 by OSA status following tonsillectomy. RESULTS: A total of 78 patients with Down syndrome whose mean age was 5.29 years at time of tonsillectomy were identified. There was no difference between best-fit curves of %BMI p95 pre-and post-tonsillectomy. There was no difference between best-fit curves of %BMI p95 in patients who saw resolution of OSA after tonsillectomy vs patients with residual OSA. CONCLUSIONS: Tonsillectomy neither alters the BMI trajectory of children with Down syndrome, nor changes differentially the risk for obesity in children whose OSA did or did not resolve after surgery.

Clinical Characteristics and Risk Factors for Developing Pulmonary Hypertension in Children with Down Syndrome.

OBJECTIVES: To determine the incidence, characteristics of, and risk factors contributing to the development of pulmonary hypertension in children with Down syndrome. STUDY DESIGN: This retrospective, review of a large cohort (n = 1242) of children with Down syndrome receiving care at a specialized referral center evaluated clinical data and serial echocardiograms from a clinic database and electronic medical records. Pulmonary hypertension characteristics and comorbidities were reviewed. Pulmonary hypertension was considered transient if echocardiographic evidence of pulmonary hypertension resolved without recurrence, persistent if no resolution, and recurrent if evidence of pulmonary hypertension returned after a period of resolution. RESULTS: The incidence of pulmonary hypertension in children with Down syndrome was 28% (n = 346). Median age at initial diagnosis was 5 days (range: 0-7067 days). Pulmonary hypertension was differentiated into transient (70%), persistent (15%), and recurrent (15%) disease. Median duration of transient pulmonary hypertension was 8 months (range: 0.1-130.2 months). Median age at recurrence was 2.5 years (range 0.2-11.5 years). Initial pulmonary hypertension diagnosis was classified as World Health Organization group I disease in 82%, with 45% associated with congenital heart disease (CHD), and 38% persistent pulmonary hypertension of the newborn (PPHN). The pulmonary hypertension recurrence rate was significant and similar for both those with initial PPHN (12%) and non-PPHN (16%). A majority (87%) of patients with recurrent pulmonary hypertension were classified as World Health Organization group III. Frequently identified comorbid conditions included CHD, obstructive sleep apnea, intermittent hypoxia, and recurrent pneumonia. CONCLUSIONS: Pulmonary hypertension is common in children with Down syndrome, is typically transient, and related to CHD or PPHN but can recur in the setting of respiratory disease such as obstructive sleep apnea, intermittent hypoxia, and recurrent pneumonia.

Levodopa-Responsive Early-Onset Parkinsonism in Down Syndrome.

Individuals with Down syndrome (DS) can develop Alzheimer's disease as early as 30 to 40 years old, but parkinsonism is rarely described. We report on a 20-year-old woman with Down syndrome and parkinsonism who responded dramatically to carbidopa-levodopa. We propose that the occurrence of parkinsonism in individuals with DS may be underreported. Recognizing and treating this condition may improve quality of life.

Morphine Pharmacokinetics in Children With Down Syndrome Following Cardiac Surgery.

OBJECTIVES: To assess if morphine pharmacokinetics are different in children with Down syndrome when compared with children without Down syndrome. DESIGN: Prospective single-center study including subjects with Down syndrome undergoing cardiac surgery (neonate to 18 yr old) matched by age and cardiac lesion with non-Down syndrome controls. Subjects were placed on a postoperative morphine infusion that was adjusted as clinically necessary, and blood was sampled to measure morphine and its metabolites concentrations. Morphine bolus dosing was used as needed, and total dose was tracked. Infusions were continued for 24 hours or until patients were extubated, whichever came first. Postinfusion, blood samples were continued for 24 hours for further evaluation of kinetics. If patients continued to require opioid, a nonmorphine alternative was used. Morphine concentrations were determined using a unique validated liquid chromatography tandem-mass spectrometry assay using dried blood spotting as opposed to large whole blood samples. Morphine concentration versus time data was modeled using population pharmacokinetics. SETTING: A 16-bed cardiac ICU at an university-affiliated hospital. PATIENTS: Forty-two patients (20 Down syndrome, 22 controls) were enrolled. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The pharmacokinetics of morphine in pediatric patients with and without Down syndrome following cardiac surgery were analyzed. No significant difference was found in the patient characteristics or variables assessed including morphine total dose or time on infusion. Time mechanically ventilated was longer in children with Down syndrome, and regarding morphine pharmacokinetics, the covariates analyzed were age, weight, presence of Down syndrome, and gender. Only age was found to be significant. CONCLUSIONS: This study did not detect a significant difference in morphine pharmacokinetics between Down syndrome and non-Down syndrome children with congenital heart disease.

Trisomy 21 causes changes in the circulating proteome indicative of chronic autoinflammation.

Trisomy 21 (T21) causes Down syndrome (DS), but the mechanisms by which T21 produces the different disease spectrum observed in people with DS are unknown. We recently identified an activated interferon response associated with T21 in human cells of different origins, consistent with overexpression of the four interferon receptors encoded on chromosome 21, and proposed that DS could be understood partially as an interferonopathy. However, the impact of T21 on systemic signaling cascades in living individuals with DS is undefined. To address this knowledge gap, we employed proteomics approaches to analyze blood samples from 263 individuals, 165 of them with DS, leading to the identification of dozens of proteins that are consistently deregulated by T21. Most prominent among these proteins are numerous factors involved in immune control, the complement cascade, and growth factor signaling. Importantly, people with DS display higher levels of many pro-inflammatory cytokines (e.g. IL-6, MCP-1, IL-22, TNF-α) and pronounced complement consumption, resembling changes seen in type I interferonopathies and other autoinflammatory conditions. Therefore, these results are consistent with the hypothesis that increased interferon signaling caused by T21 leads to chronic immune dysregulation, and justify investigations to define the therapeutic value of immune-modulatory strategies in DS.

Clinical Characteristics of Dysphagia in Children with Down Syndrome.

Aspiration is an often unrecognized comorbidity in children with Down syndrome with serious medical consequences. This retrospective chart review of swallow study reports characterizes oral and pharyngeal phase dysphagia and diet modifications on videofluoroscopic swallow studies (VFSS) in a large cohort of children with Down syndrome. A total of 158 pediatric patients (male = 95; female = 63; mean age 2.10 years, SD 3.17 years) received an initial VFSS at a pediatric teaching hospital as part of their medical care. A total of 56.3 % (n = 89) children had pharyngeal phase dysphagia with aspiration and deep laryngeal penetration occurring most frequently. Of the 61 patients who aspirated, 90.2 % (n = 55) did so silently with no cough or overt clinical symptoms. In 76.7 % of cases of pharyngeal phase dysphagia, a functional feeding plan, with use of thickened liquids or change in feeding system to control flow rate and/or bolus size, was able to be established, which allowed children to continue eating by mouth. Thickened liquids (76.7 %, n = 46) were the most effective adaptation, with change in feeding system alone effective in only 8.3 % (n = 5) cases. Oral phase dysphagia was reported in the majority of patients (63.8 %, n = 88/138); however, this was not predictive of pharyngeal phase dysphagia. Age, sex, and reason for referral, including prior clinical symptoms, did not have a statistically significant impact on the presence of dysphagia. This comprehensive review has application to clinical understanding and management of dysphagia in children with Down syndrome.