Past Seattle Children’s Studies about Craniofacial Microsomia

Study Highlight: The CAUSE Study

We would like to give a huge thank you to the hundreds of children and parents who participated in The CAUSE Study!

The Craniofacial microsomia: Accelerating Understanding of the Significance and Etiology (CAUSE) Study was a 5-year project funded by the NIH to learn more about the facial features
and genetic differences in children and young adults with differences of the ear or jaw (e.g. microtia or craniofacial microsomia).

The CAUSE Study enrolled families from the United States and South America. CAUSE study sites included:

  • Seattle Children’s Hospital in Seattle, Washington

  • Children’s Hospital Los Angeles in Los Angeles, California

  • The Children’s Hospital of Philadelphia in Philadelphia, Pennsylvania

  • University of North Carolina in Chapel Hill, North Carolina

  • Pontificia Universidad Javeriana in Bogota Colombia

  • Pontificia Universidad Javeriana in Cali, Colombia

  • Universidad ICESI in Cali, Colombia

  • Clinica Comfamiliar Risaralda in Pereira, Colombia

  • Hospital Edgardo Rebagliati in Lima, Peru

-          A total of 360 children with craniofacial microsomia and 571 parents participated in the CAUSE study.

-          Participants provided:

o   Saliva or blood (for genetic analysis)

o   Medical history data

o   Photos

-          Whole Genome or Exome Sequencing was completed on over 260 families.

Data collected from the CAUSE Study has already led to new findings and publications about the genetic cause of Craniofacial Microsomia! Here are two research articles that have been written using the data collected by the CAUSE Study:

1) Damaging variants in FOXI3 cause microtia and craniofacial microsomia - PMC (nih.gov)

2) Haploinsufficiency of SF3B2 causes craniofacial microsomia - PubMed (nih.gov)

More information about the CAUSE Study can be found on the NIH Reporter Website!

Other Past Seattle Children’s Studies

Healthcare and psychosocial experiences of individuals with craniofacial microsomia: Patient and caregivers perspectives

The purpose of this study was to get a better understanding of the healthcare and psychosocial experiences of individuals with craniofacial microsomia. To do this, we created an online survey that individuals with craniofacial microsomia and parents of children with craniofacial microsomia could complete. We also asked people what was important for them to know about craniofacial microsomia and what future research should study. What we learned from research participants in this study has helped shape the goals of our next studies.

  • Healthcare and psychosocial experiences of individuals with craniofacial microsomia: Patient and caregivers perspectives. [Link to Article] Written by Dr. Daniela Luquetti and colleagues and published in the International Journal of Pediatric Otorhinolaryngoly (2018 Apr;107:164-175).

    In Their Own Words: Caregiver and Patient Perspectives on Stressors, Resources, and Recommendations in Craniofacial Microsomia Care. [Link to Article] Written by Dr. Alexis Johns and colleagues and published in the Journal of Craniofacial Surgery (2018 Nov;29(8):2198-2205).

CFM: Longitudinal Outcomes in Children pre-Kindergarten (CLOCK)

CLOCK was the first major study to track development in children with and without craniofacial microsomia from infancy through 36 months of age. The goals of the CLOCK study included learning more about early development of children with and without craniofacial microsomia in order to better understand the needs of young children with craniofacial microsomia. CLOCK enrolled over 190 children at sites across the US (Seattle, Los Angeles, Philadelphia, Chapel Hill, and Chicago).  This study was funded in 2012 by the U.S. National Institute of Dental and Craniofacial Research (NIDCR) which is part of the U.S. National Institutes of Health (NIH). You can learn more by clicking on this project number: R01DE022438 . 

  • Evaluation of prenatal diabetes mellitus and other risk factors for craniofacial microsomia. [Link to Article] Written by Dr. Babette Siebold and colleagues and published in Birth Defects Research (2019 Jul 1;111(11):649-658).

    Neurodevelopment of Infants with and without Craniofacial Microsomia. [Link to Article] Written by Dr. Matthew Speltz and colleagues and published in the Journal of Pediatrics (2018 Jul;198:226-233).

    Methods and Challenges in a Cohort Study of Infants and Toddlers With Craniofacial Microsomia: The Clock Study. [Link to Article] Written by Dr. Daniela Luquetti and colleagues and published in the Cleft Palate-craniofacial Journal (2019 Aug;56(7):877-889).

    Facial Expressiveness in Infants With and Without Craniofacial Microsomia: Preliminary Findings.[Link to Article] Written by Dr. Zakia Hammal and colleagues and published in the Cleft Palate-craniofacial Journal (2018 May;55(5):711-720).

    Dynamics of Face and Head Movement in Infants with and without Craniofacial Microsomia: An Automatic Approach. [Link to Article] Written by Dr. Zakia Hammal and colleagues and published in Plastic and Reconstructive Surgery Global Open (2019 Jan 11;7(1):e2081).

    Behavioral Adjustment of Preschool Children With and Without Craniofacial Microsomia. [Link to Article] Written by Dr. Alexis Johns and colleagues and published in the Cleft Palate-craniofacial Journal (2021 Jan;58(1):42-53).

    Cognitive, Motor, and Language Development of Preschool Children With Craniofacial Microsomia. [Link to Article] Written by Dr. Brent Collett and colleagues and published in the Cleft Palate-craniofacial Journal ( 2021 Sep;58(9):1169-1177).

Facial Asymmetry Collaborative for Interdisciplinary Analysis and Learning (FACIAL)

The FACIAL network was established to overcome key barriers to studying craniofacial microsomia (CFM). Traditionally, medical centers have defined cases differently and followed different protocols to treat children and teens with this condition. The FACIAL team developed standardized definitions and study protocols to enable clinical research and facilitate multicenter studies in craniofacial microsomia. The network has helped conduct studies that improves our understanding of craniofacial microsomia’s causes and treatment outcomes by collaborating with healthcare professionals, investigators, individuals with craniofacial microsomia, and their families. The repository, which holds information from all our studies on craniofacial microsomia, is still active. This study was funded in 2009 by the U.S. National Institute of Dental and Craniofacial Research (NIDCR) which is part of the U.S. National Institutes of Health (NIH). You can learn more by clicking on this project number: RC1DE020270. 

  • Evaluation of ICD-9-CM codes for craniofacial microsomia. [Link to Article] Written by Dr. Daniela Luquetti and colleagues and published in Birth Defects Research. Part A, Clinical and molecular teratology (2012 Dec;94(12):990-5).

    Photographic protocol for image acquisition in craniofacial microsomia. [Link to Article] Written by Dr. Carrie Heike and colleagues and published in Head and Face Medicine (2011 Dec 30;7:25).

    MYT1 role in the microtia-craniofacial microsomia spectrum. [Link to Article] Written by Dr. Daniela Luquetti and colleagues and published in Molecular Genetics and Genomic Medicine (2020 Oct;8(10):e1401).

Phenotypic Assessment of Craniofacial Microsomia

The purpose of this study was to see if assessments of facial differences associated with craniofacial microsomia using a photograph provides similar information as an in-person clinical exam. This study was able to show that assessments using photographs are reliable when compared to assessments made during an in-person examination.

These findings made it possible for our team to collect photos at the time of study visits, instead of needing an in-person clinical assessment. This has also allowed our team to expand our research and invite interested participants (regardless of where they live) to participate! In previous research, we were limited to inviting families who lived close to our (or a collaborating site’s) location. Currently, participants who are interested in participating in our craniofacial microsomia research studies do not need to attend visits , as we are able to have families upload photos from their smartphones, and we are able to do assessments on the photos. This allows for virtual participation world-wide!

  • Reliable classification of facial phenotypic variation in craniofacial microsomia: a comparison of physical exam and photographs. [Link to Article] Written by Dr. Craig Birgfeld and colleagues and published in Head & face medicine (2016 Oct;8(10):e1401).