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RecruitingNCT02639312Updated Aug 28, 2026

Natural History of Craniofacial Anomalies and Developmental Growth Variants

An observational study in Prognathism, Retrognathism and Dentofacial Deformities, sponsored by National Institute of Dental and Craniofacial Research (NIDCR). Recruiting at 1 site in United States. Open to participants aged 2 Years to 100 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-08-28.

Sponsored by National Institute of Dental and Craniofacial Research (NIDCR) · Observational

Study type
Observational
Model
Case-control
Time perspective
Prospective
Enrollment
2,400
Ages
2 Years to 100 Years
Sex
All
01

Study summary

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

Read the 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 cone-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:

  1. To create a database with phenotypic and genetic data, collected from the long-term follow up of subjects (females and males) with craniofacial disorders and healthy volunteers
  2. To link the data with their clinical information to understand the craniofacial disorders.
02

Conditions studied

  • Prognathism
  • Retrognathism
  • Dentofacial Deformities

Keywords

  • Craniofacial
  • Microsomia
  • Mandibular
  • Facial Defects
  • Hasburg Jaw
  • Natural History
03

Who can participate

Ages eligible
2 Years to 100 Years
Sexes eligible
All
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

Inclusion criteria

For Subjects:

  • Age > 2 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.
  • >= 2 years old 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.

    ->= 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

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this study:

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 (one or the other is required to participate).

For Healthy Volunteers:

-Female volunteers who are pregnant or nursing.

04

Study design

Observational model
Case-control
Time perspective
Prospective
Enrollment
2,400 participants (estimated)

Groups and cohorts

  • 1

    hemifacial microsomia

  • 2

    mandibular prognathism

05

What researchers measure

Primary outcomes

  1. Database or registry

    using both extensive clinical evaluations, 3D cone-beam computed tomography-based geometric morphometric and cephalometric analyses, and surface morphology

    Time frame: 17 years

06

Study locations

1 of 1 sites recruiting
  • National Institutes of Health Clinical Center
    Bethesda, Maryland 20892, United States
    • For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) · Contact · ccopr@nih.gov · 800-411-1222
    Recruiting
07

References and documents

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. PubMed 9743642 ↗
  • 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. PubMed 18074368 ↗
  • 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. PubMed 19131318 ↗
  • Lee E, Crayton M, Lee JS, Almpani K. Quantitative Assessment Protocol for Facial Soft Tissue Volumetric Changes with Stereophotogrammetry. J Vis Exp. 2025 Dec 9;(226). doi: 10.3791/69204. PubMed 41460808 ↗

Individual participant data

Plan to share: Undecided

08

Registry details

Key details

Study ID
NCT02639312
Lead sponsor
National Institute of Dental and Craniofacial Research (NIDCR)
Responsible party
Sponsor
First posted
Dec 24, 2015
Start date
Apr 18, 2016
Primary completion
Dec 31, 2046 (estimated)
Completion
Dec 31, 2046 (estimated)
Last update
Aug 28, 2026

Study contacts

Pamela M Orzechowski, R.N.
Contact
ps363q@nih.gov
(301) 402-7373
Konstantinia Almpani, D.D.S.
Contact
nadine.almpani@nih.gov
(301) 827-1647
Konstantinia Almpani, D.D.S.
principal investigator · National Institute of Dental and Craniofacial Research (NIDCR)

Oversight

FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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