Natural History of Craniofacial Anomalies and Developmental Growth Variants

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:

• To establish a curated craniofacial phenomic/genomic database
• 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:

• 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
• To link the data with their clinical information to understand the craniofacial disorders.

• 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

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.