Natural History of Craniofacial Anomalies and Developmental Growth Variants

Background:

Some head and facial abnormalities are rare and present at birth. Others are more common, and may not show up until puberty. These conditions have different causes and characteristics. Researchers want to learn more about these conditions by comparing people with face, head, and neck abnormalities to family members and to healthy volunteers without such conditions.

Objectives:

To learn more about abnormal development of the face, head, and neck. To determine their genetic variants.

Eligibility:

People who have not had surgery for facial trauma:

People ages 2 and older with craniofacial abnormalities (may participate offsite)

Unaffected relatives ages 2 and older

Healthy volunteers ages 6 and older

Design:

Participants will be screened with medical history and physical exam focusing on head, face, and neck

Participants may be followed for several years. Visits may require staying near the clinic for a few days.

A visit is required for the following developmental stages, along with follow-up visits:

Age 2-6

Age 6-10

Age 11-17

Age 18 and older

Visits may include:

Medical history

Physical exam

Questionnaires

Oral exam

Blood and urine tests

Cheek swab: a cotton swab will be wiped across the inside of the cheek several times.

Cone beam CT scan (CBCT): x-rays create an image of the head, face, teeth, and neck. Participants will

stand still or sit on a chair for about 20 minutes while the scanner rotates around the head.

Photos of the head and face

Offsite participants will provide:

Copies of medical and dental records

Leftover tissue samples from previous surgery

Blood sample or cheek swab

Study Overview

• Status: Recruiting
• Conditions: Prognathism; Dentofacial Deformities; Retrognathism

Detailed Description

Study Description:

This is a natural history study that will examine craniofacial anomalies that affect the normal development of the facial skeleton, including birth defects and dentofacial developmental abnormalities that express themselves with the growth of the individual. Craniofacial anomalies may be rare and present at birth, such as hemifacial microsomia (1 in every 7500 live births), or common, such as dentofacial deformities including the Habsburg Jaw or mandibular prognathism (1% of the US population) that becomes apparent as a child enters puberty. These are striking disorders as they involve the face and surrounding structures, which is a focal point of self-identity and are intimately tied to quality of life and daily function.

Objectives:

Primary Objective:

To characterize and determine genetic variants of rare and common craniofacial anomalies

Secondary Objectives:

1. To establish a curated craniofacial phenomic/genomic database
2. To collect data related to clinically-indicated procedures and care performed at the NIH

Endpoints:

Primary Endpoint:

Phenotypic and genomic characterization of craniofacial anomalies will be performed. Phenotypes from affected subjects and healthy volunteers will be assessed using extensive clinical evaluations, 3D one-beam computed tomography-based geometric morphometric, cephalometric analyses and surface morphology. Genetic variants will be identified through genomic analysis and compared with genetic patterns obtained from healthy volunteers.

Secondary Endpoints:

To create a database with phenotypic and genetic data, collected from long term follow up of subjects (females and males) with craniofacial disorders and healthy volunteers, and to link the data with their clinical information to understand the craniofacial disorders.

• Study Type: Observational
• Enrollment (Estimated): 2400

Contacts and Locations

• Study Contact: Name: Pamela M Orzechowski, R.N.; Phone Number: (301) 402-7373; Email: ps363q@nih.gov
• Study Contact Backup: Name: Janice S Lee, DDS, MD; Phone Number: (301) 827-1647; Email: leejs2@mail.nih.gov

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Recruiting
      • National Institutes of Health Clinical Center
      • Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR); Phone Number: TTY dial 711 800-411-1222; Email: ccopr@nih.gov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

-Subjects w/craniofacial anomalies or dentofacial deformities -Families of subjects with craniofacial anomalies or dentofacial deformities -Case Controls

Description

• INCLUSION CRITERIA:

For Subjects:

• Age greater than or equal to 2 to less than or equal to 100 with craniofacial anomalies/abnormalities. Affected family member (defined as an individual with a demonstrable relationship (any family relationship no matter how distant) with the above subject in the pedigree) who expresses craniofacial anomalies will be classified as a subject.
• Able to provide consent or in the case, of minors, have a legally-authorized representative to provide consent.

For Unaffected Family Members:

• These family members are defined as individuals with a demonstrable relationship (any family relationship no matter how distant) with a proband subject by pedigree who do not express craniofacial anomalies.
• greater than or equal to 2 years old to less than or equal to 100 years old.
• Able to provide consent or in the case, of minors, have a legally-authorized representative to provide consent.

For Healthy Volunteers:

• In good general health.
• Greater than or equal to 6 years old to < 100 years old..
• Able to provide consent or in the case, of minors, have a legally-authorized representative to provide consent.
• Absence of a craniofacial congenital anomaly or malocclusion.
• No family history of a craniofacial syndrome.

EXCLUSION CRITERIA:

For All Participants:

• A history of facial trauma requiring surgical treatment and facial reconstruction.
• Refusal for both genetic testing and CBCT imaging. Participants must agree to at least one of the two (both are not required to participate).

For Healthy Volunteers:

-Female volunteers who are pregnant or nursing.

Study Plan

How is the study designed?

Design Details

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

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
1; hemifacial microsomia
2; mandibular prognathism

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Database or registry	using both extensive clinical evaluations, 3D cone-beam computed tomography-based geometric morphometric and cephalometric analyses, and surface morphology	17 years

Collaborators and Investigators

• Sponsor: National Institute of Dental and Craniofacial Research (NIDCR)
• Investigators: Principal Investigator: Janice S Lee, DDS, MD, National Institute of Dental and Craniofacial Research (NIDCR)

Publications and helpful links

General Publications

• Proffit WR, Fields HW Jr, Moray LJ. Prevalence of malocclusion and orthodontic treatment need in the United States: estimates from the NHANES III survey. Int J Adult Orthodon Orthognath Surg. 1998;13(2):97-106.
• Cruz RM, Krieger H, Ferreira R, Mah J, Hartsfield J Jr, Oliveira S. Major gene and multifactorial inheritance of mandibular prognathism. Am J Med Genet A. 2008 Jan 1;146A(1):71-7. doi: 10.1002/ajmg.a.32062.
• Frazier-Bowers S, Rincon-Rodriguez R, Zhou J, Alexander K, Lange E. Evidence of linkage in a Hispanic cohort with a Class III dentofacial phenotype. J Dent Res. 2009 Jan;88(1):56-60. doi: 10.1177/0022034508327817.

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): April 18, 2016
• Primary Completion (Estimated): April 18, 2036
• Study Completion (Estimated): April 18, 2036

Study Registration Dates

• First Submitted: December 23, 2015
• First Submitted That Met QC Criteria: December 23, 2015
• First Posted (Estimated): December 24, 2015

Study Record Updates

• Last Update Posted (Actual): March 26, 2024
• Last Update Submitted That Met QC Criteria: March 23, 2024
• Last Verified: March 22, 2024

More Information

Terms related to this study

• Keywords: Natural History; Craniofacial; Microsomia; Mandibular; Facial Defects; Hasburg Jaw
• Additional Relevant MeSH Terms: Congenital Abnormalities; Musculoskeletal Diseases; Stomatognathic Diseases; Stomatognathic System Abnormalities; Jaw Abnormalities; Jaw Diseases; Maxillofacial Abnormalities; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Mandibular Diseases; Retrognathia; Prognathism; Dentofacial Deformities
• Other Study ID Numbers: 160040; 16-D-0040

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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