Skull

The skull is formed from the lateral plate mesoderm (the neck region), the paraxial mesoderm, and the neural crest (Fig. 4-1). The bony skull is formed by one of two mechanisms: intramembranous ossification or endochondral ossification. Skull development is divided into two parts: the viscerocranium and the neurocranium. The viscerocranium forms the bones of the face, whereas the neurocranium forms the bones of the cranial base and the cranial vault. The neurocranium can be divided into the membranous neurocranium and the cartilaginous neurocranium. The anterior fontanel (bregma) has a wide range of expected closure between 4 and 26 months of age. The posterior fontanel (lambda) generally closes between 1 and 2 months of age.

From the first pharyngeal pouch are formed the maxillary process, the mandibular process, and the second pharyngeal arch. Many bones are derived from the maxillary arch, including the maxilla, the temporal bones, the zygoma, the palatine bone, the lacrimal bone, the vomer, the nasal bones, and the inferior nasal concha. The mandibular process forms the mandible, the sphenomandibular ligament, the malleus, and the incus. From the second pharyngeal arch are formed the styloid process, the stapes, the hyoid bone, and the stylohyoid ligament.

Face

The face is formed mainly from the neural crest, which makes three “swellings” that surround the stomodeum (Fig. 4-2). The three swellings are the frontonasal prominence, the maxillary prominence (from the first pharyngeal arch), and the mandibular prominence (from the first pharyngeal arch).

Lateral to the frontonasal prominence, there are two areas of ectoderm that form the nasal placodes, which invaginate in the center to form the nasal pits. The placodes that invaginate create ridges of tissues on either side of the pits. The ridges are called the lateral nasal prominence and the medial nasal prominence. The fusion of the medial nasal prominence at the midline results in the formation of the intermaxillary segment.

Palate

The palate is formed by the primary palate (intermaxillary segment) and the secondary palate (protrusions from the lateral prominences) (Fig. 4-3). The intermaxillary segment (primary palate) is the initial portion of the palate to develop. It contains the central and lateral incisors. Swellings of the maxillary prominence form shelves that project medially but that are separated by the tongue. When the tongue no longer occupies the space between the palatal shelves, these processes fuse together to form the secondary palate. The primary and secondary palatal tissues all meet at the incisal foramen. The primary and secondary palates and the nasal septum fuse to form the definitive palate.

Deficiencies of Midline Tissue Structures

Holoprosencephalies involve variable deficiencies of midline tissues. These structural deficiencies have been documented to occur early during embryologic development.16,18,23,27 They may range from severe brain anomalies to simple absence or hypoplasia of the corpus callosum. Severe facial anomalies such as cyclopia, ethmocephaly, and cebocephaly are always associated with severe holoprosencephaly, and they are incompatible with life. This can also be true of premaxillary agenesis; however, in some instances, patients may survive for several months or even years. There are reported cases of premaxillary agenesis with normal head circumference and no brain abnormalities (i.e., without holoprosencephaly), although these patients sometimes have mild mental deficiencies. Syntelencephaly (the absence or hypoplasia of the corpus callosum or absent or hypoplastic olfactory tracts and bulbs) is compatible with life and should thus be treated. Associated facial anomalies include retinal colobomas, cleft lip, cleft palate, single maxillary central incisor, and midface deficiencies. Holoprosencephaly has multiple causes and includes many chromosomal types, many monogenetic disorders, and at least three teratogens.

Deficiencies and Anomalies of Neural Crest Origin

Most of the tissues of the face, including the muscular and skeletal components, are derived from the mesoderm. Interestingly, throughout the rest of the body, these components (i.e., muscle and skeleton) are derived from an ectodermal origin.¹⁹ The facial mesodermal elements develop from the neural crest and then migrate downward beside the neural tube and laterally under the surface ectoderm. When the neural crest cells have completed migration to their specific location, then facial development is dominated by specific growth centers, the formation of visceral structures (e.g., brain, eyes, sinuses), and the differentiation of the tissue layers. Facial anomalies of neural crest origin are thought to arise when the neuroepithelium has apoptosis (i.e., the cells die).²⁵ This results in less neuroepithelium to migrate through into the facial locations and to ultimately differentiate. Current knowledge of Treacher Collins syndrome indicates that this is not a migration problem but simply a lack of cells to migrate (Figs. 4-4 and 4-5).

Teratogens that are known to result in head and neck (neural crest) congenital anomalies include cytomegalovirus (microcephaly, hydrocephaly, microophthalmia); Dilantin (cleft lip and palate); vitamin D excess (premature suture closure); Valium (cleft lip and palate); Rubella virus (microophthalmia, cataracts, deafness); and thalidomide (variations of hemifacial microsomia and Treacher Collins syndrome). Despite these known relationships, teratogenic agents are not the most frequent causes of these syndromes.¹

The branchial arch syndromes are neural crest anomalies that comprise an etiologically heterogeneous group of disorders.¹⁴ They account for only a small percentage of the patients who present to the surgeon or orthodontist in need of jaw reconstruction. The best known of these are hemifacial microsomia, its variant Goldenhar syndrome, and Treacher Collins syndrome.¹⁴ Hemifacial microsomia affects aural, zygomatic, and mandibular growth at a minimum (Fig. 4-6). The disorder may be mild or severe, and it is generally limited to one side of the face. However, bilateral involvement, with more severe expression on one side, is also known to occur. Goldenhar syndrome, which is a variant of hemifacial microsomia, also includes epibulbar dermoids and vertebral anomalies. Involvement is often but not always limited to the face. There may be cardiac, renal, skeletal, and central nervous system anomalies (see Chapter 28). At a minimum, patients with Treacher Collins syndrome demonstrate the physical findings of bilateral zygomatic hypoplasia, down-slanting palpebral fissures, malformed ears, and micrognathia (see Chapter 27). Inheritance occurs in an autosomal-dominant fashion, and expressivity varies (see Figs. 4-4 and 4-5). The syndrome maps to 5q32-q33.1, and mutations in the TCOF1 gene are of the nonsense, insertion, deletion, or splice-site types.^14,30,139

Clefting of the Lip and Palate

The most prevalent congenital defect of dentofacial development is clefting of the lip, the palate, or both (Figures 4-7 through 4-19). This condition occurs in approximately 1 in 1000 whites, 1 in 500 Asians, and 1 in 2000 blacks.²⁷ The etiology of clefts is often complex and multifactorial. Evidence supports the view that genetic factors are associated with orofacial clefting.³⁷ In twins with cleft lips and palates, concordance is far greater among monozygotic twins (40%) as compared with dizygotic twins (4.2%). In twins with isolated cleft palate, concordance is also higher among monozygotic twins (35%) as compared with dizygotic twins (7.8%).¹³⁸ Nevertheless, orofacial clefting is heterogeneous and variable, and it is likely determined by a number of major genes, minor genes, environmental factors, and a developmental threshold.³⁷ Some syndromes associated with clefting in which specific gene mutations have been identified include van der Woude syndrome (IRF6), popliteal pterygium syndrome (IRF6), autosomal-recessive cleft palate/ectodermal dysplasia (PVRL1), hypodontia/clefting (MSX1), Hay-Wells syndrome (TP63), and cleft palate/ankyloglossia (TBX22). These mutations explain only about 5% of clefting cases, with an additional 10% to 15% of cases explained by variations involving the IRF6 gene.¹¹⁰ Although orofacial clefting is caused by a malformation, the development of secondary deformities of the jaws after birth is well known (see Chapters 32, 33, and 34). For the most part, maxillary hypoplasia in patients with orofacial clefts is felt to be the result of palate surgical interventions carried out during infancy and early childhood and not from the primary congenital anomaly. Although van der Woude and Stickler are just 2 of more than 100 clefting syndromes, they demonstrate the importance of having an awareness of associated anomalies to assist with family counseling and to achieve effective reconstruction.

Achondroplasia

Achondroplasia is the most common condition associated with severe disproportionate short stature.²² The cause of this condition is the failure during development of the primary growth cartilages of the limbs and the cranial base. This results in short arms and legs as well as a characteristic midface deficiency or deformity that is most visually notable at the nasofrontal process.

Most affected individuals do well but attain a final height of only approximately 4 feet. The condition is known to be caused by mutations on the FGFR3 (fibroblast growth factor receptor 3) gene.²² Eighty percent of reported cases are sporadic, whereas 20% are familial. Although craniosynostosis is not a typical feature, three cases with craniosynostosis have been reported.

Premature Suture Closure of the Cranial Vault and Skull Base

The flat bones of the cranial vault develop from mesenchymal condensations over the developing brain (see Fig. 4-1). These bones grow primarily via the apposition of bone at their edges. The regions in which the cranial bony edges collide are called sutures. In addition to appositional growth at the edges (i.e., suture growth), cranial vault development also occurs through the process of remodeling (i.e., resorption and deposition).¹⁷ Continued separation of the sutures during the process of the apposition of bone at the edges is also important to the normal growth of the bones of the cranial base and the midface.

Synostosis is a condition of premature fusion (i.e., the arrest of appositional growth at the bone edges) that occurs before the associated visceral structures (e.g., brain, eyes) complete growth.¹⁷ When this happens, there is distortion or deformity of the shape of the affected bones and possible compression of the underlying visceral structures (i.e., the brain). Premature closure of the cranial vault sutures (craniosynostosis) that do not extend into the cranial base will have minimal effects on the maxillofacial form (e.g., metopic, unilateral coronal, and sagittal suture synostosis; Figures 4-20, 4-21, and 4-22). However, prematurely fused cranial vault sutures that extend into the cranial base will also affect midfacial growth and development (e.g., Crouzon, Apert, and Pfeiffer syndrome; Figures 4-23 through 4-26; see Chapter 30).

Overgrowth Syndromes and Anomalies

Acromegaly is caused by an anterior pituitary tumor that secretes excessive growth hormone after the normal completion of growth.²¹ The response of specific growth centers to abnormal serum levels of growth hormone is the overdevelopment of the hands, the feet, the supraorbital ridges, and the mandible. When there is excessive mandibular growth, the position of the teeth within the bone and the occlusion are also effected. An enlarged sella turcica (i.e., the resorption of bone in response to pituitary tumor expansion) can be seen on a lateral cephalometric radiograph or a computed tomography scan (Fig. 4-27). Excess growth hormone causes the proliferation of the condylar cartilage of the mandible, thereby resulting in the bilateral symmetric forward projection of the jaw. This overgrowth continues until the serum growth hormone levels return to normal. Unfortunately, the resultant skeletal deformities persist. Other examples of maxillomandibular overgrowth include hemifacial hypertrophy (see Chapter 31), hemimandibular hyperplasia, and hemimandibular elongation (see Chapter 22).

Muscle and Soft-Tissue Effects on Skeletal Growth

Experimental animal research and clinical observational studies confirm that the influences of the mandibular rest posture, the neck rest posture, and the tongue and lip rest position of the affected individual’s eventual facial morphology are real and more important than the effects of intermittent muscle contracture (see Chapters 8 and 10).^128–130 It is also known that functional stresses that are placed on the skeleton will increase bone density.^113,114,118 A corollary is that, during periods of inactivity (e.g., mandibular and neck rest posture), skeletal demineralization occurs.

Erupting teeth carry alveolar bone with them. Therefore, forces that counteract the normal eruption of teeth can shape the dental arches and the alveolar processes of both the maxilla and the mandible.5,101–105,107,109,111,126,140 Experimental studies confirm that pressure against the active eruption of the teeth that is maintained for 4 to 6 hours can affect tooth movement and initiate bone remodeling (see Chapter 5). Habits such as finger or thumb sucking, which apply consistent pressure against the teeth, can have the same effect on the shaping of the dental arches (see Figs. 4-31 and 4-32). It seems as though the intensity (i.e., the amount of force) against the teeth is less important than the duration (i.e., the number of hours per day) with regard to causing this effect.

It has been confirmed that the postural position of the tongue at rest (e.g., the mandible open with the constant protrusion of the tongue) rather than where the tongue is placed during function (e.g., a tongue-thrust swallowing habit) is most important for determining the eventual position of the teeth and the morphology of the dento-alveolar complex.61,121 The intermittent forces that are generated against the teeth during chewing, swallowing, and speaking are documented to be more than heavy enough to produce tooth movement. However, during these normal functions, the force is not maintained long enough at any point in time to have an appreciable effect on the position of the teeth or the morphology of the bone.³⁵ Even repetitive intermittent “abnormal” tongue and lip contraction with resulting pressure on the teeth during swallowing and speaking (i.e., tongue thrusting)—despite their frequency—do not sum up to the number of hours of force required to produce a pathologic effect. By contrast, even very light forces sustained for a long duration (i.e., the tonic contracture of masticatory muscles to maintain mandibular posture) can affect both the path of tooth eruption and jaw development.^8,94

It is known that muscles of different size and force that attach to the mandible at specific locations will result in characteristic ridges and contours (e.g., gonial angles, coronoid process, genial tubercle).12,13 For patients with the condition known as masseteric muscle hypertrophy, there is excess bone proliferation at the masseter muscle’s point of attachment along the inferior border of the mandible (i.e., the gonial angle ridge) in response to greater than average muscle forces.⁴³ By contrast, in patients with muscular dystrophies (i.e., hypotonic cerebral palsy, Moebius syndrome with cranial nerve palsy), the ramus may be short, and the gonial angles appear to be underdeveloped as a result of the limited muscle forces applied to these same regions.¹⁰⁰

The lips, cheeks, and tongue contain muscles in their deep layers that exert varied pressures against the teeth and the alveolar process. They normally do so with a constant level of tone while at rest as well as during dynamic function. These light (tone) forces applied for a long duration are known to cause tooth movement and remodeling of the alveolar process. It is the “resting” postural pressures of these structures (i.e., lips, cheeks, tongue, and muscles), the presence of para-oral habits (i.e., thumb sucking, pencil biting; see Figs. 4-31 and 4-32), and the man-made and controlled orthodontic pressure that can exert the long duration of light force at the periodontal ligament that is required to move teeth.⁵⁵ When the difference between applied orthodontic forces and pressures of the tongue, cheek, and lips that counteract those forces applied to the periodontal ligament becomes great enough for sustained periods of time, tooth movement will occur. Another example of dental adaptation is seen when the constant strong force of the tongue is juxtaposed with intrinsic weaker bilabial (i.e., upper and lower lip) muscle tone forces.¹³⁵ This results in the predictable dental compensations (i.e., proclined maxillary and mandibular incisors) observed in patients with bimaxillary dento-alveolar protrusion (see Chapter 24). This also explains the consistent dental compensations that are typically observed in patients with specific developmental dentofacial deformities such as long face growth pattern (see Chapter 21 and Fig. 4-33) or isolated mandibular deficiency (see Chapter 19).¹²²

Severe scar contracture of the anterior neck and lower lip soft tissues from a burn that occurred during childhood will also affect mandibular morphology. The soft-tissue contracture will distort ongoing skeletal growth and cause the mandible to be retrusive, with an obtuse angle. The chin region of the mandible will grow with increased vertical length and without sagittal prominence, and there will be an anterior open-bite malocclusion. This deformity and its surgical correction were first described by Simon Hullihen in 1849 (see Chapter 2 and Fig. 2-19).

When an electric burn to an oral commissure occurs during childhood and results in soft-tissue contracture with microsomia, the constant soft-tissue forces against the teeth will distort the shape of the dental arch and the alveolar process. There will be anterior dental crowding, tipping of the incisors, and malocclusion.

With the congenital absence of part or most of the tongue, there will be a characteristic V-shaped deficiency or dysmorphology of the mandibular dental arch (e.g., hypoglossia–hypodactylia syndrome; Fig. 4-35).¹⁵ In the presence of a volumetrically enlarged tongue (e.g., vascular malformation, hemangioma, neurofibromatosis, Proteus syndrome, Beckwith-Wiedemann syndrome), there will be dento-alveolar effects that result in spaces between the teeth (Fig. 4-36). The lower anterior teeth will be flared, and the overall mandibular arch form will be enlarged. The important factor that causes these dental compensations and arch form deformities is the sustained and constant rest forces of the oversized tongue on the teeth and bone and not what the tongue does when it is in motion.

In the individual with a normal tongue volume and neuromotor capability, it is known that the rest position of the tongue in the mouth is primarily influenced by respiratory factors.⁷³ It is the rest position of the tongue that influences the pattern of dentofacial development rather than the position of the tongue during function.

In the presence of chronic nasal obstruction, a typical long face growth pattern with anterior open-bite malocclusion is likely to occur. In these circumstances, a speech therapist may have success with teaching the individual altered movement of the tongue for the formation of more accurate voluntary independent speech sounds.⁹⁰ However, unless the anterior open bite and the nasal obstruction are corrected, the myofunctional therapy will not allow the individual to reliably position his or her tongue, lips, teeth, and mandible for correct articulation during rapid conversational speech (see Chapter 8).

In the skeletal Class III adult patient (i.e., a retrusive maxilla with relative mandibular excess) who undergoes successful orthognathic correction, a normal oral cavity volume and a normal occlusion are established. Interestingly, in most cases, the tongue position and lip posture will then naturally adapt to the new morphology.80,81

Clinical observation confirms that, when an individual with a longstanding dentofacial deformity undergoes successful reconstruction, it is generally not necessary to retrain the tongue with active myofunctional therapy. This only needs to occur under the following conditions: 1) when the tongue volume is truly excessive (e.g., vascular malformation, neurofibromatosis) 2) when there is the presence of intrinsic neuromotor dysfunction (e.g., cerebral palsy) or 3) when the nasal airway remains obstructed and a failure of tongue adaptation is seen.⁶³

Respiration Patterns and Their Effects on Skeletal Growth

Harvold conducted primate experiments that were designed to test hypotheses regarding the relationship between nasal obstruction, mouth breathing, mandibular rest posture, tongue rest position, jaw growth, and dental malocclusion.49–54 He created an experimental model in growing rhesus monkeys (Macaca mulatta) to study these relationships. To do this, he completely obstructed the nasal passages in the study subjects with silicone nose plugs. The experiments showed that the monkeys adapt to total nasal obstruction in two different ways. Predominantly, the experimental animals maintained an open-mouth posture with tongue protrusion. Interestingly, some adapted to a forced oral airway by holding the upper and lower teeth close together but with wide lip separation. Nevertheless, both adaptive mandibular, tongue, and lip positioning patterns gradually resulted in maxillomandibular dysmorphology and dental malocclusion that was notably different from that seen in the control animals.

In the experimental animals, morphologic changes that occurred in the lips, tongue, dentition, jaws, and mandibular posture were documented by the research team through cephalometric measurements as well as through electromyographic and behavioral findings. Harvold’s cephalometric findings documented changes in facial height (e.g., of the naso-palatal plane and the symphysis-palatal plane) and alterations in mandibular morphology.

As stated, a minority of animals adapted to the nasal airway blockage by holding their teeth together with wide lip separation (rather than maintaining an open-mouth posture with tongue protrusion) while still breathing through their mouths. This subgroup showed the least change in jaw morphology and dental alignment.

The observed morphologic and occlusal changes were most extreme when the mandible constantly remained open, with tongue protrusion (i.e., an open-mouth posture). The adaptive lowering of the mandible (with clockwise rotation) to achieve effective oral respiration was followed by secondary changes in the maxilla, including a downward displacement (i.e., vertical lengthening) of the alveolar process in conjunction with excess extrusion of the teeth. When molar (posterior) hypereruption was significantly greater than incisor hypereruption, an anterior open-bite malocclusion developed (Fig. 4-37).¹²⁷

It became apparent to Harvold that the changes in mandibular shape and the direction of mandibular growth (i.e., clockwise rotation) observed in a majority of the experimental monkeys were dependent on the adaptive activity of the facial, tongue, jaw, and neck muscles in response to respiratory need. Interestingly, in Harvold’s experimental animal model, there was no indication of abnormal bony apposition on the condyles in association with the forced oral respiratory pattern. The apposition of new bone on the condyles continued (in the usual way) independently of aberrant mandibular positioning or open-mouth posture.¹⁰⁷

In review, the growing experimental animals studied by Harvold coped with nasal obstruction by changing neck, tongue, facial, and masticatory muscle tone, thereby resulting in alterations in mandibular posture and tongue position.44,45,55 The animals typically did this in one of two different ways but always with the goal of maintaining adequate respiration. This resulted in varied but consistent secondary changes in the maxillomandibular morphology (i.e., developmental jaw deformity) and dental compensations (i.e., malocclusion). The measured lower facial height increase that occurred in the presence of a constant open-mouth posture was primarily the result of maxillary molar—and, to a lesser extent, incisor dental—hypereruption (e.g., long face growth pattern).

Harvold also reviewed the human observation studies of Linder-Aronson and colleagues and found that they paralleled his experimental animal research.68–70,75–78 Their clinical research established that nasal obstruction with forced mouth breathing (i.e., open-mouth posture) in humans is frequently associated with maxillary dental extrusion, a steeper than normal mandibular plane, anterior open-bite malocclusion (i.e., the hypereruption of the molars is greater than that of the incisors), and increased lower anterior facial height. Similar to Harvold’s experimental monkeys, growing humans may develop different neuromotor adaptations to cope with nasal obstruction and the need to maintain adequate respiration. The secondary skeletal and dental morphologic deviations will therefore vary, but they tend to occur in a predictable long face growth pattern (see Chapter 21).^{39,125,133,134}

Humans with severe hypoplasia of the maxilla, a retropositioned palate and a restricted nasal airway, as are seen in patients with Crouzon or Apert syndrome, also become dependent on oral respiration (see Chapter 30).⁴ With Crouzon or Apert syndrome, the individual’s neck is often maintained in hyperextension with an open-mouth posture, the protrusion of the tongue, and the clockwise rotation of the mandible; this head and neck posture is compensatory to support respiration. During the day, this compensatory posture may be sufficient, but it becomes inadequate at night and results in obstructive sleep apnea (see Chapter 26).⁴ When these compensatory adaptive changes occur during childhood, they contribute to additional secondary maxillomandibular skeletal dysmorphology with growth that further affects the occlusion (see Chapter 30).^7,33,115 This is an example of a congenital midface deformity that is further influenced by the environment.

Congenital Myopathies and Effects on Skeletal Growth

Individuals with congenital myopathies constitute a heterogeneous subgroup of patients with congenital neuromuscular disorders in which the pathology is attributable to defects in the muscle fibers rather than in the neurons. Congenital fiber-type disproportions are rare congenital myopathies that are considered slow or nonprogressive. Patients with these conditions, like those with other types of primary myopathies, will generally exhibit facial features that often result in what is described as a “myopathic face.” The “myopathic face” has many similarities to the “adenoid face” that is seen in children with a blocked nasal airway due to enlarged adenoids and other intranasal obstructions, which result in an open-mouth posture. These abnormal human maxillomandibular growth patterns are also consistent with the findings reported by Harvold when rhesus monkeys were forced to maintain an open-mouth posture during jaw growth, as described previously in this chapter. The “myopathic face” findings described by Lehman and colleagues include characteristics of an increased lower anterior facial height, incompetent lips, a high-arched palate, and often anterior open-bite malocclusion (Figs. 4-37 and 4-38).⁶⁶ Clinical human and animal model studies confirm that these features are to be expected in the presence of an open-mouth posture during jaw growth, no matter what the cause. Although blocked nasal breathing is the most common cause of an open-mouth posture during growth, clearly congenital myopathies that also result in an open-mouth posture will produce the same facial dysmorphology.

1. The mandibular condyle: Proliferating cartilage at the base of the fibrocartilage layer that covers the articular surface results in mandibular growth. At the completion of mandibular growth, the fibrocartilage layer is replaced by bone.

2. The outer surfaces of the ramus: Extensive remodeling of the mandible through the apposition of bone on the posterior and outer surfaces along with resorption on the anterior and inner surfaces is known to occur and is influenced by muscle forces and the compression of the associated soft tissues (e.g., tongue volume) within the mouth.

3. The alveolar process: New alveolar bone is added only as individual teeth develop and erupt into the arch.

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