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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.

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.

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.

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.

Using exome sequencing, we have identified de novo variants in MAPK8IP3 in 13 unrelated individuals presenting with an overlapping phenotype of mild to severe intellectual disability. The de novo variants comprise six missense variants, three of which are recurrent, and three truncating variants. Brain anomalies such as perisylvian polymicrogyria, cerebral or cerebellar atrophy, and hypoplasia of the corpus callosum were consistent among individuals harboring recurrent de novo missense variants. MAPK8IP3 has been shown to be involved in the retrograde axonal-transport machinery, but many of its specific functions are yet to be elucidated. Using the CRISPR-Cas9 system to target six conserved amino acid positions in Caenorhabditis elegans, we found that two of the six investigated human alterations led to a significantly elevated density of axonal lysosomes, and five variants were associated with adverse locomotion. Reverse-engineering normalized the observed adverse effects back to wild-type levels. Combining genetic, phenotypic, and functional findings, as well as the significant enrichment of de novo variants in MAPK8IP3 within our total cohort of 27,232 individuals who underwent exome sequencing, we implicate de novo variants in MAPK8IP3 as a cause of a neurodevelopmental disorder with intellectual disability and variable brain anomalies.