The facial morphology in Down syndrome: A 3D comparison of patients with and without obstructive sleep apnea.

Obstructive sleep apnea (OSA) occurs at a high prevalence in patients with Down syndrome (DS). A polysomnogram, which is often cumbersome and challenging, remains the gold standard method of diagnosing OSA. OSA in patients with DS is often attributed to skeletal and soft-tissue structural alterations that are characteristic of the DS phenotype; as such, we hypothesized that assessing anthropometric facial measurements may be predictive of OSA in patients with DS. We used the 3dMDface sterophotography system to capture and create 3D facial images, and we subsequently identified facial landmarks using a single, experienced investigator and utilizing proprietary software to calculate inter-landmark distances and angles. We compared our findings with similar data for neurotypically developing participants. We further compared the findings in participants with DS with and without OSA. Participants with DS had maxillomandibular hypoplasia with smaller 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.

A predictive model for obstructive sleep apnea and Down syndrome.

Obstructive sleep apnea (OSA) occurs frequently in people with Down syndrome (DS) with reported prevalences ranging between 55% and 97%, compared to 1-4% in the neurotypical pediatric population. Sleep studies are often uncomfortable, costly, and poorly tolerated by individuals with DS. The objective of this study was to construct a tool to identify individuals with DS unlikely to have moderate or severe sleep OSA and in whom sleep studies might offer little benefit. An observational, prospective cohort study was performed in an outpatient clinic and overnight sleep study center with 130 DS patients, ages 3-24 years. Exclusion criteria included previous adenoid and/or tonsil removal, a sleep study within the past 6 months, or being treated for apnea with continuous positive airway pressure. This study involved a physical examination/medical history, lateral cephalogram, 3D photograph, validated sleep questionnaires, an overnight polysomnogram, and urine samples. The main outcome measure was the apnea-hypopnea index. Using a Logic Learning Machine, the best model had a cross-validated negative predictive value of 73% for mild obstructive sleep apnea and 90% for moderate or severe obstructive sleep apnea; positive predictive values were 55% and 25%, respectively. The model included variables from survey questions, medication history, anthropometric measurements, vital signs, patient's age, and physical examination findings. With simple procedures that can be collected at minimal cost, the proposed model could predict which patients with DS were unlikely to have moderate to severe obstructive sleep apnea and thus may not need a diagnostic sleep study.

Thyroid dysfunction in patients with Down syndrome: Results from a multi-institutional registry study.

The goals of this undertaking were to assess the outcomes of thyroid screening tests and adherence to thyroid screening guidelines across five Down syndrome (DS) specialty clinics in various states. Data related to thyroid screening were collected for 663 individuals across five clinics specializing in the comprehensive care of individuals with DS for a period of 1 year. Of the 663 participants, 47.7% of participants had a TSH and free T4 ordered at their DS specialty clinic visit. Approximately 19.0% (60/316) had a new thyroid disorder diagnosis made. We conclude that a sizable proportion of the patients with DS are not up-to-date on current guidelines when they present to a DS specialty clinic, while adherence to thyroid screening guidelines helps facilitate early diagnoses. Hypothyroidism is prevalent in the population, consistent with reported literature. DS specialty clinics can help patients stay current on screening guidelines.

Detecting celiac disease in patients with Down syndrome.

The main purposes of this undertaking were to determine how often patients with Down syndrome (DS) are screened for celiac disease (CD) across five DS specialty clinics, which symptoms of CD are most often reported to DS specialty providers at these clinics, and, how many individuals were diagnosed with CD by these clinics. This was accomplished by following 663 individuals with DS for 1 year, across five clinics in different states specializing in the comprehensive care of people with DS. Of the 663 participants, 114 individuals were screened for CD at their visit to a DS specialty clinic. Protracted constipation (43.2%) and refractory behavioral problems (23.7%) were symptoms most often reported to DS specialty providers. During the 1 year study period, 13 patients screened positive for CD by serology. Of those, eight underwent duodenal biopsy, and three were diagnosed with CD. We conclude that CD is an important consideration in the comprehensive care of individuals with DS. However, while symptoms are common, diagnoses are infrequent in DS specialty clinics. © 2016 Wiley Periodicals, Inc.

National down syndrome patient database: Insights from the development of a multi-center registry study.

The Down Syndrome Study Group (DSSG) was founded in 2012 as a voluntary, collaborative effort with the goal of supporting evidenced-based health care guidelines for individuals with Down syndrome (DS). Since then, 5 DS specialty clinics have collected prospective, longitudinal data on medical conditions that co-occur with DS. Data were entered by clinical staff or trained designees into the National Down Syndrome Patient Database, which we created using REDCap software. In our pilot year, we enrolled 663 participants across the U.S., ages 36 days to 70 years, from multiple racial and ethnic backgrounds. Here we report: (i) the demographic distribution of participants enrolled, (ii) a detailed account of our database infrastructure, and (iii) lessons learned during our pilot year to assist future researchers with similar goals for other patient populations.

Urinary biomarkers and obstructive sleep apnea in patients with Down syndrome.

STUDY OBJECTIVES: The study aimed to compare urinary biomarkers in patients with Down syndrome (DS) with and without obstructive sleep apnea (OSA) to those of age- and sex-matched neurotypically developing healthy controls (HC). We further investigated whether we could predict OSA in patients with DS using these biomarkers. METHODS: Urine samples were collected from 58 patients with DS the night before or the morning after their scheduled overnight polysomnogram or both, of whom 47 could be age- and sex-matched to a sample of 43 HC. Concentrations of 12 neurotransmitters were determined by enzyme-linked immunosorbent assay. Log-transformed creatinine-corrected assay levels were normalized. Normalized z-scores were compared between patients with DS vs. HC, between patients with DS with vs. without OSA, and to derive composite models to predict OSA. RESULTS: Most night-sampled urinary biomarkers were elevated among patients with DS relative to matched HC. No urinary biomarker levels differed between patients with DS with vs. without OSA. A combination of four urinary biomarkers predicted AHI > 1 with a positive predictive value of 90% and a negative predictive value of 68%. CONCLUSIONS: Having DS, even in the absence of concurrent OSA, is associated with a different urinary biomarker profile when compared to that of HC. Therefore, while urinary biomarkers may be predictive of OSA in the general pediatric population, a different approach is needed in interpreting urinary biomarker assays in patients with DS. Certain biomarkers also seem promising to be predictive of OSA in patients with DS. No clinical trial was indicated in the undertaking of this work.

Craniofacial features as assessed by lateral cephalometric measurements in children with Down syndrome.

OBJECTIVE: The objective of the present study is to examine the craniofacial development of patients with Down syndrome (DS) and compare them with a neurotypical population. METHODS: This study is a cross-sectional analysis of lateral cephalometric radiographs of participants with DS. The study population consisted of children and young adults with DS aged 3-25 years. Cephalometric data were summarized by age and sex. Raw and normalized z-scores were computed. One-sample t tests were used to test whether mean z-scores differed from zero. The demographic characteristics between those with or without lateral cephalograms among all study participants were compared by Fisher's exact tests. RESULTS: The study sample comprised of 27 participants with DS. Study subjects demonstrated a class III skeletal pattern. This was more pronounced in the older age groups as compared to younger age groups. Subjects also had an increased proportionate lower anterior face height to total facial height compared to normative standards. Gonial angles, mandibular plane angles, and airway measurements increased with age. CONCLUSIONS: Patients with Down syndrome present typically with class III skeletal pattern and long lower anterior facial heights. In patients with Down syndrome, comprehensive phase of orthodontic treatment may be best initiated following cessation of growth.