An important aspect of understanding the craniofacial complex is a comprehensive characterization of the growth and development of the structures involved. In 2011, Dr. Sherwood received funding from the National Institute of Dental and Craniofacial Research (NIH) to conduct a pilot study on craniofacial growth (R03 DE021435 Longitudinal Modeling of Craniofacial Growth Trajectories).
This study originally used the craniofacial data collected in Dr. Sherwood’s earlier genetic study to characterize growth trajectories of craniofacial traits. This type of statistical modelling leverages the full power of the longitudinal data available from the Fels Longitudinal Study. The success of that pilot study resulted in a new study, funded by the NIDCR (R01DE024732) in 2015, collecting data from eight of the largest growth studies ever conducted in North America.
The goal of this research project is to conduct a detailed longitudinal analysis of the growth of the craniofacial complex. Precise characterization of ontogenetic trajectories across the functional/developmental components of the craniofacial complex will provide fundamental baseline information to both basic researchers and clinicians. Craniofacial anomalies are among the most common congenital defects. Additionally, the prevalence of orthodontic treatment exceeds 30% according to national averages. The clinical significance of this region is not restricted to physical health as even small variations in anatomy may significantly impact feelings of self-worth. Fortunately, many craniofacial disorders can be successfully treated during childhood with surgical approaches or orthodontic applications. The success of these treatments can be maximized through a comprehensive understanding of craniofacial growth including general patterns of growth, the timing of changes in the rate of development, and the degree of morphological integration during periods of growth.
This study, now known as the Craniofacial Growth Consortium Study (CGCS) has collected data from 17,256 of these radiographs taken from the ages of 3 months to 25 years on 2,100 individuals. The median number of radiographs per person is nine, which provides an unparalleled longitudinal record for the study of growth.
For diagnostic and prognostic purposes, the Center has begun producing population percentile reference standards relative to both chronological and skeletal age using quantile regression, individualized reference percentiles given a past measurement, and prediction of future growth percentiles given a current measurement. This work was presented at the International Conference of Childhood Bone Health in Dublin, Ireland (July, 2022).
See the International Conference of Childhood Bone Health poster
Research
Human Craniofacial Growth Studies
Working on a project like the Craniofacial Growth Consortium (CGCS) presents numerous challenges. The CGCS includes data from eight studies spanning several decades and spread across North America. The data in the CGCS come from lateral cephalographs (head radiographs) and each of the original studies used slightly different protocols when taking the cephalographs.
What is the CGCS?
As an introduction to the CGCS, it is important to provide the history of the original studies, identify the challenges in working with archival images and provide details of how researchers overcame the obstacles. Most importantly, the collection was examined to see if there were clear differences between the studies that could be attributed to population differences or possibly protocol differences between studies. This paper, published in The Anatomical Record, provides that information and validates the combining of the separate studies into a single large study.
Sherwood, R.J. H.S. Oh, M. Valiathan, K.P. McNulty, D.L. Duren, R.P. Knigge, A.M. Hardin, C.L. Holzhauser, K.M. Middleton. 2021. Bayesian Approach to Longitudinal Craniofacial Growth: The Craniofacial Growth Consortium Study. Anat. Rec. 304: 991-1019. https://doi.org/10.1002/ar.24520.
When does cranial growth stop?
The adolescent height growth spurt, where a teen might grow 6 inches or more in a short period of time, is a familiar occurrence to most people. While changes in facial measures will not be that dramatic, regions of the skull do experience a growth spurt during adolescence. Important clinical milestones of this spurt include the age at peak growth velocity and the cessation of growth. For some clinical treatments of facial dysmorphologies, it is critical that the patient has completed growth. In this paper, researchers focused on the estimation of growth cessation using different statistical methods.
Hardin, A.M., R.P. Knigge, H.S. Oh, M. Valiathan, D.L. Duren, K.P. McNulty, K.M. Middleton, R.J. Sherwood. 2021. Estimating Craniofacial Growth Cessation: Comparison of Asymptote- and Rate-based Methods. Cleft Palate Craniofac. J. 59:230-238. https://doi.org/10.1177/10556656211002675.
Do people’s faces grow differently?
Differential patterns of craniofacial growth are important sources of variation that can result poor bite or malocclusion. Understanding the timing of growth milestones and morphological change associated with adult malocclusions is critical for developing individualized orthodontic growth modification strategies. To identify patterns in the timing and geometry of growth, researchers used two statistical approaches to examine growth curves and anatomy in nine different facial categories.
Knigge, R. P., et al. (2022). "Craniofacial Growth and Morphology Among Intersecting Clinical Categories." Anat. Rec. 305: 2175-2206. https://doi:10.1002/ar.24870
Richard Sherwood’s full publication list can be found here: https://www.ncbi.nlm.nih.gov/myncbi/1fCTgEabw6fQd/bibliography/public/
Funding
- 2021- present University of Missouri. TRIUMPH Program. R.J. Sherwood (MPI), D.L. Duren (MPI), K.M. Middleton (Co-I). Maturation-based Prediction of Craniofacial Growth.
- 2019-2020 F32 DE029104 National Institute of Dental and Craniofacial Research. National Institutes of Health. A.M. Hardin (PI), R.J. Sherwood, J.L. Cook (Co-Sponsors), D.L. Duren, E.V. Leary, A. Muzaffar, M. Valiathan, K. Aldridge (Collaborators). Ontogenetic integration in individuals with craniofacial anomalies.
- 2020-2021 American Association for Anatomy Postdoctoral Fellowship. Ryan P. Knigge (PI), R.J. Sherwood (Sponsor). Morphological integration in orofacial clefts during adolescence.
- 2015-2022 R01 DE024732 National Institute of Dental and Craniofacial Research (NIH)., R.J. Sherwood (Co-PI), H.S. Oh (MPI), K.M. Middleton, K.P. McNulty, M. Valiathan (co-I) Craniofacial Growth Prediction in Different Facial Types.
- 2019-2022 R01 R01 DE024732-06S1 National Institute of Dental and Craniofacial Research (NIH)., R.J. Sherwood (Co-PI), H.S. Oh (Co-PI), K.M. Middleton, K.P. McNulty, M. Valiathan (co-I) Administrative Supplement. Craniofacial Growth Prediction in Different Facial Types: Bayesian and Machine Learning Models.
- 2011- 2014, R03DE021435 National Institute of Craniofacial and Dental Research (NIH). R.W. Nahhas, P.I., R.J. Sherwood, Co-I. Longitudinal Modeling of Craniofacial Growth Trajectories.
- 2008-present American Association of Orthodontists Foundation. L.A. Will, J.A. McNamara, S. Baumrind, T.E. Southard, D.A. Covell, C. Evans, R.J. Sherwood, G.F. Currier, M.G. Hans, B.D. Tompson, E. Richardson. The AAOF Craniofacial Growth Legacy Collection.
Human Craniofacial Genetics
Research on the genetic basis for human craniofacial anomalies has successfully identified several of the major genes involved in craniofacial development, thanks to the wealth of detailed genetic information that is rapidly becoming available for human dental and cranial disorders. It is also clear, however, that advances in the genetics of craniofacial disorders have provided ambiguous answers to important questions regarding the genetic architecture of normal and abnormal craniofacial variation. The Center’s research seeks to make clear the genetic underpinnings of anatomical variation of the human and non-human craniofacial complex.
Two projects investigated the genetic architecture of craniofacial variation in humans. Both projects described the morphology in the area of interest such as the mandible or face. These measures are subjected to quantitative genetic analyses allowing researchers to identify
1) the relative influence genes have on a trait;
2) the proportion of which two traits are controlled by the same gene or sets of genes; and
3) to begin to localize the chromosomal regions harboring genes influencing variation.
The first project examined traits identified on lateral cephalographs of participants in the Fels Longitudinal Study. The Fels Longitudinal Study is the world’s largest- and longest-running study of human growth, development and body composition. Measurements describing the basicranium, face and neurocranium were taken from the lateral cephalographs available in the study archives. The second project examines, in detail, the morphology of the dentition and the jaws in a human population from the small village of Jiri, Nepal. This population has limited access to orthodontic procedures and thus provides a unique opportunity to study the morphological integration of this region.
Funding
- 2013 - 2015 Boonshoft School of Medicine, Emerging Science Seed Grant. R.J. Sherwood (PI), D.L. Duren, K.P. McNulty (Co-I). The Geometry and Architecture of Craniofacial Inheritance.
- 2009 - 2014 R01 DE018497 National Institute of Dental and Craniofacial Research (NIH). R.J. Sherwood, P.I., D.L. Duren, J. Subedi, B. Towne, S. Williams-J. Blangero VandeBerg Co-I. Genetic Architecture of the Dentognathic Complex.
- 2005 - 2010 R01 DE016692 National Institute of Dental and Craniofacial Research (NIH). R.J. Sherwood, P.I., D.L. Duren, B. Towne, R. Siervogel Co-I. Genetic Architecture of the Human Craniofacial Complex.
Baboon Craniofacial Genetics
In addition to the Center's project examining the genetic architecture of the human craniofacial complex, researchers conducted a parallel study in a non-human primate, the baboon. This study leveraged the resources available in the pedigreed population of baboons at the Southwest National Primate Research Center in San Antonio, Texas, by collecting cranial metrics from over 850 baboons. Results from this work have appeared in the journal Genetics and several edited volumes. The study was successful in demonstrating a significant genetic influence on all traits and in identifying a number of significant quantitative trait loci (QTL).
Funding
- 2005 - 2008 R21 DE016408 National Institute of Dental and Craniofacial Research (NIH). R.J. Sherwood, P.I., D.L. Duren, M.C. Mahaney, B. Towne co-I. Genetic Architecture of the Baboon Craniofacial Complex.
- 2004-2006 Southwest National Primate Research Center Pilot Study Program (NIH P51 RR13986 to the Southwest National Primate Research Center). R.J. Sherwood, P.I., D.L. Duren, M.C. Mahaney, B. Towne Co-I. Genetic Influences on Craniofacial Growth in the Baboon.
