Elsevier

Seminars in Orthodontics

Volume 11, Issue 4, December 2005, Pages 219-226
Seminars in Orthodontics

A Gradient of Potential for Modifying Craniofacial Growth

https://doi.org/10.1053/j.sodo.2005.07.006Get rights and content

This review evaluates the hypothesis that a skeletal structure’s response to epigenetic and environmental stimuli is directly proportional to its maturity status. We focus on the craniofacial complex because it exhibits a wide growth maturity gradient and is, therefore, ideally suited to test the hypothesis of differential response potential to the same stimulus across structures. Because it is a major epigenetic factor controlling somatic growth and maturation, emphasis is placed on studies pertaining to growth hormone (GH) deficits/supplementation. GH deficiency has profound effects on overall body size/maturation and it produces characteristic abnormalities in the craniofacial complex. Human and, especially, animal studies, show that (1) the various components of the craniofacial complex exhibit substantially different response potentials to hormonal deficits, (2) growth deficits associated with GH deficits are greatest for the most mature structures; less mature craniofacial structures display the greatest potential for future growth deficits, and (3) the less mature structures have the greater potential for catch-up following GH supplementation. We conclude that the craniofacial growth maturity gradient provides a basis for better understanding variability in response potential across craniofacial structures.

Section snippets

Relative Craniofacial Growth

Differences in the relative growth of the various craniofacial components have long been established.8, 9 Among the first to quantify relative facial growth differences was Hellman,10 who described a lengthening and deepening of the face as a whole over time; regionally, he noted relative lengthening posteriorly and relative widening and deepening inferiorly. Hellman’s cross-sectional comparisons indicated that, from early ages on, facial width reaches maturity earlier than facial depth, which

The GH-Deficient Child

Growth hormone deficiency (GHD) has profound effects on overall body size and maturation. Although growth deficits occur earlier,21 children are normally 2 to 5 years of age before growth failure is detected. Even at those young ages, skeletal maturation is already delayed by approximately 2 years.17, 19, 22, 23, 24, 25, 26 Stature is affected even more than skeletal maturation.18, 25, 27 Simply to be diagnosed as GHD, the child’s growth rate must fall below the 3rd percentile.

Craniofacial Growth Status of Untreated GHD Children

GHD produces characteristic differences in the craniofacial complex. Children with GHD have an immature facial appearance,22, 24, 28, 29 with nose shape characterized as “saddled.”28, 30 The maxilla is generally small and recessed.30, 31, 32 The mandible is also small, retrognathic and hyperdivergent,30, 32, 33 with open-bite tendencies.29 The gonial angle, mandibular plane, and palatal plane angles tend to be larger than normal.32 Posterior facial height is proportionately smaller than

Growth Changes of Children Treated for GHD

Treatment of GHD produces “catch-up” growth, with substantial increases in skeletal maturation and somatic growth, especially during the first year of replacement therapy.18, 19, 25, 38, 39, 40 Studies evaluating craniofacial growth of treated GHD children are conflicting due to small sample sizes and relatively weak designs. In addition, most studies evaluating craniofacial growth of treated children with GHD have been cross-sectional, which limits their ability to describe actual growth

Animal Models for Studying Relative Growth

For both practical and ethical reasons, it is not possible to perform prospective clinical trials evaluating GH-induced catch-up growth in humans. Animal studies are needed to control extraneous sources of variation, compare treated with untreated subjects, and to evaluate the effects of stopping treatment.

VandeBerg and colleagues recently established that wild-type Lewis rats between 4 and 9 weeks of age provide excellent models for studying relative craniofacial growth.51 They showed that

Animal Studies Evaluating GH Supplementation

A number of animal studies have shown that GH supplementation has different effects on the various craniofacial components. Collins and colleagues, who used hypophysectomized rats, reported greater effects of GH on the growth of the lower than upper jaw, with growth of the posterior mandible contributing greatly to the effects observed.55 Miura and colleagues also showed a differential increase in dimensions of the craniofacial complex following injections of GH in 21 day-old GH-normal rats.56

Possible Mechanisms of Postnatal Growth Gradients

Variability in response potential across craniofacial components is important because it provides information about morphological integration. Cheverud’s quantitative genetic analyses have demonstrated that covariances across structures reflect developmental and functional relationships.57, 58, 59 If, as he suggested, the phenotypic covariance structure provides an indirect measure of the genotypic covariance structure, the CFGMG reflects genetic relationships between component parts, which

Conclusions

  • 1

    The craniofacial growth maturity gradient provides a basis for better understanding how environmental and epigenetic factors produce variability across structures.

  • 2

    Unlike Scammon’s typological model of differential growth, which focuses on differences between structures, the craniofacial growth maturity gradient emphasizes the morphological integration of the component parts.

  • 3

    The various components of the craniofacial complex exhibit substantially different response potentials to environmental

References (67)

  • J.M. Cheverud

    Quantitative genetics and developmental constraints on evolution by selection

    J Theor Biol

    (1984)
  • C.H. Waddington

    The modular principle and biological form

  • J.P. Scott

    Critical periods in organizational processes

  • J. van Limborgh

    Factors controlling skeletal morphogenesis

  • J.T. Bruer

    A critical and sensitive period primer

  • C.R. Stockard

    The artificial production of a single median cyclopian eye in the fish embryo by means of sea water solutions of magnesium chloride

    Arch Entwicklungsmech

    (1907)
  • C.M. Child

    The Origin and Development of the Nervous System

    (1921)
  • H. Welcker

    Kraniologische mitteilungen

    Arch Anthropol

    (1866)
  • M. Holl

    Über gesichsbildung

    Mitt Anthropol Ges Wien

    (1898)
  • M. Hellman

    The face in its developmental career

    Dent Cosmos

    (1935)
  • R.E. Scammon

    The measurement of the body in childhood, in The Measurement of Man

    (1930)
  • B. Baughan et al.

    The pattern of facial growth before and during puberty as shown by French-Canadian girls

    Ann Hum Biol

    (1979)
  • P.H. Buschang et al.

    A craniofacial growth maturity gradient for males and females between four and sixteen years of age

    Am J Phys Anthrop

    (1983)
  • P. Weiss

    Principles of Development

    (1969)
  • P.H. Buschang et al.

    Craniofacial growth and size patterns during postnatal development

    Growth

    (1983)
  • A.K. Laird et al.

    Growth in timean interpretation of allometry

    Growth

    (1968)
  • R. Rubenstein et al.

    Endocrine

    Sci Am Med V-Pituitary

    (1989)
  • R.D.G. Milner et al.

    Experience with human growth hormone in Great Britainthe report of the MRC working party

    Clin Endocrinol

    (1979)
  • A. Perlman et al.

    Summary report. October 1991

    Genentech national cooperative growth study

    (1991)
  • R. Hernandez et al.

    Hand radiographic measurements in growth hormone deficiency before and after treatment

    Am J Roentgen

    (1977)
  • J.D. Wilson et al.

    Williams Textbook of Endocrinology

    (1992)
  • K. Takano et al.

    Oro-maxillofacial development in patients with GH deficiency and in normal short children

    Endocr Jpn

    (1986)
  • H. Guyda et al.

    Medical Research Council of Canada—therapeutic trial of human growth hormonefirst 5 years of therapy

    Can Med Assoc J

    (1975)
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