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A Novel Approach to Dysmorphology to Enhance the Phenotypic Classification of Autism Spectrum Disorder in the Study to Explore Early Development

Abstract

The presence of multiple dysmorphic features in some children with autism spectrum disorder (ASD) might identify distinct ASD phenotypes and serve as potential markers for understanding causes and prognoses. To evaluate dysmorphology in ASD, children aged 3–6 years with ASD and non-ASD population controls (POP) from the Study to Explore Early Development were evaluated using a novel, systematic dysmorphology review approach. Separate analyses were conducted for non-Hispanic White, non-Hispanic Black, and Hispanic children. In each racial/ethnic group, ~ 17% of ASD cases were Dysmorphic compared with ~ 5% of POP controls. The ASD–POP differential was not explained by known genetic disorders or birth defects. In future epidemiologic studies, subgrouping ASD cases as Dysmorphic vs. Non-dysmorphic might help delineate risk factors for ASD.

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Notes

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    https://www.cdc.gov/healthyweight/bmi/calculator.html.

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    https://www.causascientia.org/math_stat/ProportionCI.html.

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Acknowledgments

The authors thank the participating families and the many staff and scientists from all sites who contribute to the Study to Explore Early Development (SEED). Specifically, the authors would like to acknowledge the following study staff from SEED who assisted in the data collection for the dysmorphology assessment: from CA SEED, Ms. Katherine Chau, Dr. Arthur Grix, Ms. Vickie Hefferman, Ms. Lucy Murillo, Dr. Jean Sakimura, Dr. Khin Win, and Dr. Dana Won; from CO SEED, Ms. Kristina Hightshoe, Ms. Mary Murphy, Dr. Ann Reynolds, Ms. Ann Ribe, Ms. Katie Szalewski, and Ms. Gabriella Yates; from GA SEED, Ms. Basudha Chaudhuri, Ms. Karen Clay, Ms. Phyllis Cook-Stillwell, Ms. Tracy Johnson, Ms. Ashleigh McCraw, Ms. Charmaine McKenzie, Ms. Julia Richardson, Ms. Robin Tate-Sparks, and Ms. Shawanna Taylor; from MD SEED, Ms. Martyna Galazka, Ms. Pam Gillin, Ms. Ashley Graham, Ms. Katie Lewis, Dr. Deepa Mennon, Ms. Julie Rusyniak, and Ms. Katie Voss; from NC SEED, Mr. Craig Clement, Ms. Betsy Glaser, Mr. Matt Herr, Mr. Eric Johnson, and Ms. Karina Yelin; and from PA SEED, Ms. Tina Almadinejad, Ms. Jessica Beauvais, Ms. Megan Carolan, Mr. Christopher Colameco, Ms. Casara Ferretti, Ms. Kathleen Lesko, Dr. Susan Levy, Ms. Rita Mack, Ms. Elizabeth McCaffrey, Ms. Donna McDonald-McGinn, Ms. Megan Ott, Ms. Michelle Petrongolo, Ms. Saba Qasmieh, Ms. Sarah Woldoff, and Ms. Jordana Woodford. The authors acknowledge Dr. Arthur Grix for developing and testing the Dysmorphology Review Form for dysmorphology assessment of the mouth, lips, and teeth. The authors acknowledge the following SEED study staff who assisted with data entry of dysmorphology reviews: Mr. Christopher Colameco, Ms. Vickie Hefferman, Mr. Joel Rothwell, and Ms. Gabriella Yates. The authors acknowledge the following SEED study staff from the SEED Data Coordinating Center for developing the data-entry interfaces for dysmorphology assessment: Mr. Michael Babcock, Mr. Patrick Thompson, Mr. Alex Walworth, and Mr. Maurice Wong. This research is supported by the Centers for Disease Control and Prevention, Centers for Autism and Developmental Disabilities Research, through six cooperative agreements (COs): CO# U10DD000180, Colorado Department of Public Health/University of Colorado School of Medicine; CO# U10DD000181, Kaiser Foundation Research Institute (CA); CO# U10DD000182, University of Pennsylvania; CO# U10DD000183, Johns Hopkins University; CO# U10DD000184, University of North Carolina at Chapel Hill; and CO# U10DD000498, Michigan State University. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

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SKS participated in conceiving and designing the study, performed dysmorphology assessments, developed and oversaw the analytic plan, performed a portion of the data analysis, interpreted the data, and drafted and revised the manuscript. LHT participated in development of the analytic plan, performed the majority of the data analysis, including the sensitivity analysis, and participated in data interpretation and reviewing and revising the manuscript for important intellectual content. ASA, ERE, JEH-F, NJLM, MCS, AC-HT, and EHZ participated in study design, performed dysmorphology assessments, participated in data interpretation, and reviewed and revised the manuscript for important intellectual content. AAA, MY-A, and LAS participated in conceiving and designing the study, interpreting the data, and reviewing and revising the manuscript for important intellectual content. All authors read and approved the final manuscript.

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Correspondence to Stuart K. Shapira.

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Shapira, S.K., Tian, L.H., Aylsworth, A.S. et al. A Novel Approach to Dysmorphology to Enhance the Phenotypic Classification of Autism Spectrum Disorder in the Study to Explore Early Development. J Autism Dev Disord 49, 2184–2202 (2019). https://doi.org/10.1007/s10803-019-03899-0

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Keywords

  • Autism spectrum disorder
  • Birth defects
  • Dysmorphic features
  • Dysmorphology
  • Genetic disorders
  • Morphologic anomalies
  • Phenotypic classification
  • Race/ethnicity