Craniofacial Microsomia: Accelerating Understanding of the Significance and Etiology (CAUSE)

The CAUSE study is a multicenter study, with domestic (n=4) and international (n=6) study sites. Children and young adults (ages 0-18) who have microtia and/or craniofacial microsomia and their parents are invited to participate. Children and parents are asked to provide a DNA sample (blood or saliva) and are asked to upload a few photos of their face. Parents are asked a short interview. Participants are able to participate from home or at one of four domestic sites.

Study Overview

• Status: Completed
• Conditions: Craniofacial Microsomia; Goldenhar Syndrome; Microtia; Microtia-Anotia; OAVS; OAV Syndrome; Hemifacial Microsomia

• Study Type: Observational
• Enrollment (Actual): 935

Contacts and Locations

Study Locations

• Colombia
  • Bogotá, Colombia
    • Pontificia Universidad Javeriana
  • Cali, Colombia
    • ICESI
  • Cali, Colombia
    • Pontificia Universidad Javeriana
  • Pereira, Colombia
    • Clínica Comfamiliar Risaralda
• Peru
  • Lima, Peru
    • Hospital Edgardo Rebagliati Martins
• Spain
  • Madrid, Spain
    • Instituto de Genética Médica y Molecular (INGEMM)
• United States
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 90027
      • Children's Hospital of Philadelphia
  • Washington
    • Seattle, Washington, United States, 98101
      • Seattle Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (Child, Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

All CFM cases, their parents, and their relatives regardless of their sex, race, or ethnicity. The prospective case samples will likely be drawn from outpatient clinics and medical centers, as well as CFM-related social medial networks.

Description

INCLUSION:

Cases:

• Participant with CFM is 0-18 years of age

• Participant has diagnosis of at least one of the following conditions:

  • Microtia
  • Anotia
  • Facial asymmetry AND preauricular tag(s)
  • Facial asymmetry AND facial tag(s)
  • Facial asymmetry AND epibulbar dermoid
  • Facial asymmetry AND macrostomia (i.e., lateral cleft)
  • Preauricular tag AND epibulbar dermoid
  • Preauricular tag AND macrostomia
  • Facial Tag AND epibulbar dermoid
  • Macrostomia AND epibulbar dermoid
• Participant's parent or legal guardian has provided written informed consent prior to enrollment into study (for participants younger than 18 years of age).
• Participant speaks a language in which they are eligible for consent at their enrolling site

Parents:

• Parent participant is the biological parent of a case participant already eligible and participating in the CAUSE study. Non-genetic parents will be interviewed about their child's known prenatal and genetic family history but will not be asked to provide DNA or have facial photographs taken.
• Participant speaks a language in which they are eligible for consent at their enrolling site

Other relatives:

• Other relatives participants, of any age, are related biologically to a case participant already eligible and participating in the CAUSE study from a multiplex family (multiple affected individuals with CFM).
• Participant speaks a language in which they are eligible for consent at their enrolling site

EXCLUSION:

Cases:

• Participant is diagnosed with a known syndrome that involves microtia and underdevelopment of the jaw (Townes-Brocks, Treacher-Collins, Branchiootorenal, Nager, or Miller syndromes).
• Participant has abnormal chromosome studies (karyotype).
• Participant has mandibular asymmetry due to deformational plagiocephaly or torticollis.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identify Genetic Variants	To identify genetic variants related to the CFM spectrum using whole genome sequencing	Through study completion, an average of 1 year.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterize phenotype	To characterize the detailed phenotype in individuals with CFM	Through study completion, an average of 1 year.
Characterize markers	To characterize ancestry markers in individuals with CFM	Through study completion, an average of 1 year.
Coding and non-coding variants	To assess coding and non-coding variants in selected candidate genes in individuals with CFM	Through study completion, an average of 1 year.

Collaborators and Investigators

• Sponsor: Seattle Children's Hospital
• Collaborators: Children's Hospital of Philadelphia; University of North Carolina, Chapel Hill; Children's Hospital Los Angeles; Instituto de Investigación Hospital Universitario La Paz; Pontificia Universidad Javeriana; Clinica Comfamiliar Risaralda; Universidad Icesi; Hospital Nacional Edgardo Rebagliati Martins
• Investigators: Principal Investigator: Carrie Heike, MD, MS, Seattle Children's

Study record dates

Study Major Dates

• Study Start (Actual): February 23, 2018
• Primary Completion (Actual): November 30, 2021
• Study Completion (Actual): August 30, 2023

Study Registration Dates

• First Submitted: April 11, 2020
• First Submitted That Met QC Criteria: April 16, 2020
• First Posted (Actual): April 17, 2020

Study Record Updates

• Last Update Posted (Actual): April 22, 2024
• Last Update Submitted That Met QC Criteria: April 18, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease; Congenital Abnormalities; Musculoskeletal Diseases; Otorhinolaryngologic Diseases; Ear Diseases; Bone Diseases; Fetal Diseases; Pregnancy Complications; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Growth Disorders; Bone Diseases, Developmental; Mandibulofacial Dysostosis; Craniofacial Dysostosis; Dysostoses; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Syndrome; Fetal Growth Retardation; Goldenhar Syndrome; Congenital Microtia
• Other Study ID Numbers: 17-601-E

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Investigators do not plan to share, as CFM is a rare disease and could be potentially identifiable.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No