The Etiology of Orthodontic Problems
Malocclusion is a developmental condition. In most instances, malocclusion and dentofacial deformity are caused, not by some pathologic process, but by moderate (occasionally severe) distortions of normal development. Occasionally, a single specific cause is apparent, for example, in mandibular deficiency secondary to a childhood fracture of the jaw or the characteristic malocclusion that accompanies some genetic syndromes. More often, these problems result from a complex interaction among multiple factors that influence growth and development, and it is impossible to describe a specific etiologic factor (Figure 5-1).
FIGURE 5-1 From a broad perspective, only about one-third of the U.S. population has normal occlusion, while two-thirds have some degree of malocclusion. In the malocclusion group, only a small minority (not more than 5%) have problems attributable to a specific known cause; the remainder are the result of a complex and poorly understood combination of inherited and environmental influences.
Although it is difficult to know the precise cause of most malocclusions, we do know in general what the possibilities are, and these must be considered when treatment is considered. In this chapter, we examine etiologic factors for malocclusion under three major headings: specific causes, hereditary influences, and environmental influences. The chapter concludes with a perspective on the interaction of hereditary and environmental influences in the development of the major types of malocclusion.
Defects in embryologic development usually result in death of the embryo. As many as 20% of early pregnancies terminate because of lethal embryologic defects, often so early that the mother is not even aware of conception. Although most defects in embryos are of genetic origin, effects from the environment also are important. Chemical and other agents capable of producing embryologic defects if given at the critical time are called teratogens. Most drugs do not interfere with normal development or, at high doses, kill the embryo without producing defects, and therefore are not teratogenic. Teratogens typically cause specific defects if present at low levels but if given in higher doses, do have lethal effects. Teratogens known to produce orthodontic problems are listed in Table 5-1.
|Aspirin||Cleft lip and palate|
|Cigarette smoke (hypoxia)||Cleft lip and palate|
|Cytomegalovirus||Microcephaly, hydrocephaly, microphthalmia|
|Dilantin||Cleft lip and palate|
|Ethyl alcohol||Central midface deficiency|
|13-cis Retinoic acid (Accutane)||Similar to craniofacial microsomia and Treacher Collins syndrome|
|Rubella virus||Microphthalmia, cataracts, deafness|
|Thalidomide||Malformations similar to craniofacial microsomia, Treacher Collins syndrome|
|Toxoplasma||Microcephaly, hydrocephaly, microphthalmia|
|Valium||Similar to craniofacial microsomia and Treacher Collins syndrome|
|Vitamin D excess||Premature suture closure|
There are five principal stages in craniofacial development (Table 5-2), and effects on the developing face and jaws can arise during each stage:
|Stage||Time in humans (postfertilization)||Related syndromes|
|Germ layer formation and initial organization of structures||Day 17||Fetal alcohol syndrome (FAS)|
|Neural tube formation||Days 18-23||Anencephaly|
|Origin, migration, and interaction of cell populations||Days 19-28||Craniofacial microsomia
Mandibulofacial dysostosis (Treacher Collins syndrome)
|Formation of organ systems
|Cleft lip and/or palate, other facial clefts
|Final differentiation of tissues||Day 50-birth||Achondroplasia
Synostosis syndromes (e.g., Crouzon’s, Apert’s)
The best example of a problem that can be traced to the very early first and second stages is the characteristic facies of fetal alcohol syndrome (FAS; Figure 5-2). This is due to deficiencies of midline tissue of the neural plate very early in embryonic development caused by exposure to very high levels of ethanol. Although such blood levels can be reached only in extreme intoxication in chronic alcoholics, the resulting facial deformity and developmental delay occur frequently enough to be implicated in many cases of midface deficiency.1 In these unfortunate children, the delay in dental development matches the skeletal delay.2
Many of the problems that result in craniofacial anomalies arise in the third stage of development and are related to neural crest cell origin and migration. Since most structures of the face are ultimately derived from migrating neural crest cells (Figure 5-3), it is not surprising that interferences with this migration produce facial deformities. At the completion of the migration of the neural crest cells in the fourth week of human embryonic life, they form practically all of the loose mesenchymal tissue in the facial region that lies between the surface ectoderm and the underlying forebrain and eye and most of the mesenchyme in the mandibular arch. Most of the neural crest cells in the facial area later differentiate into skeletal and connective tissues, including the bones of the jaw and the teeth.
FIGURE 5-3 Diagrammatic lateral sections of embryos at 20 and 24 days, showing formation of the neural folds, neural groove, and neural crest. A, At 20 days, neural crest cells (pink) can be identified at the lips of the deepening neural groove, forerunner of the central nervous system. B, At 24 days, the neural crest cells have separated from the neural tube and are beginning their extensive migration beneath the surface ectoderm. The migration is so extensive and the role of these neural crest cells is so important in formation of structures of the head and face that they can almost be considered a fourth primary germ layer.
The importance of neural crest migration and the possibility of drug-induced impairment of the migration have been demonstrated clearly by unfortunate experience. In the 1960s and 1970s, exposure to thalidomide caused major congenital defects, including facial anomalies in thousands of children. In the 1980s, severe facial malformations related to the anti-acne drug isotretinoin (Accutane) were reported. The similarities in the defects make it likely that both these drugs affect neural crest cells. Retinoic acid plays a crucial role in the ontogenesis of the midface, and recent work suggests that loss of retinoic acid receptor genes affects postmigratory activity of crest cells, clarifying the timing of Accutane effects.3 The danger with isotretinoin is that it affects a developing embryo before the mother knows she is pregnant.
Altered development of cells derived from the neural crest also has been implicated in Treacher Collins syndrome (Figure 5-4), which is characterized by a generalized lack of mesenchymal tissue and now known to be due (at least in some instances) to mutations in a specific gene (TCOF1) that lead to loss of a specific exon.4
FIGURE 5-4 In the Treacher Collins syndrome (also called mandibulofacial dysostosis), a generalized lack of mesenchymal tissue in the lateral part of the face is the major cause of the characteristic facial appearance. Note the underdevelopment of the lateral orbital and zygomatic areas. The ears also may be affected. Patient at age 12 before (A) and immediately after (B) surgical treatment to advance the midface. Note the ear deformity that usually is concealed by hair. C and D, Age 16. Note the change in the lateral orbital margins.
Craniofacial microsomia (formerly called hemifacial microsomia) is characterized by a lack of development in lateral facial areas. Typically, the external ear is deformed and both the ramus of the mandible and associated soft tissues (muscle, fascia) are deficient or missing (Figure 5-5). Although facial asymmetry is always seen (thus the former name), cranial as well as facial structures are affected. The cause is loss of neural crest cells (for an unknown reason) during migration. Neural crest cells with the longest migration path, those taking a circuitous route to the lateral and lower areas of the face, are most affected, whereas those going to the central face tend to complete their migratory movement, so midline facial defects, including clefts, rarely are part of the syndrome.5
FIGURE 5-5 In craniofacial microsomia, both the external ear and the mandibular ramus are deficient or absent on the affected side. (From Proffit WR, White RP, Sarver DM. Contemporary Treatment of Dentofacial Deformity. St. Louis: Mosby; 2003.)
Neural crest cells migrating to lower regions are important in the formation of the great vessels (aorta, pulmonary artery, aortic arch), and they also are likely to be affected by problems in crest cell migration. For this reason, defects in the great vessels (as in the tetralogy of Fallot) are common in children with craniofacial malformations.
The most common congenital defect involving the face and jaws, second only to clubfoot in the entire spectrum of congenital deformities, is clefting of the lip, palate, or (less commonly) other facial structures. Clefts arise during the fourth developmental stage. Exactly where they appear is determined by the locations at which fusion of the various facial processes failed to occur (Figures 5-6 and 5-7), and this in turn is influenced by the time in embryologic life when some interference with development occurred.
FIGURE 5-6 Scanning electron micrographs of mouse embryos (which are very similar to human embryos early in embryogenesis), showing the stages in facial development. A, Early formation of the face, about 24 days after conception in the human. B, At a stage equivalent to about 31 days in the human, the medial and lateral nasal processes can be recognized alongside the nasal pit. C, Fusion of the median nasal, lateral nasal, and maxillary processes forms the upper lip, and fusion between the maxillary and mandibular processes establishes the width of the mouth opening. This stage is reached at about 36 days in humans. (Courtesy Dr. K. Sulik.)
FIGURE 5-7 Schematic representations of fusion of the facial processes. A, Diagrammatic representation of structures at 31 days, when fusion is just beginning. B, Relationships at 35 days, when the fusion process is well advanced. C, Schematic representation of the contribution of the embryonic facial processes to the structures of the adult face. The medial nasal process contributes the central part of the nose and the philtrum of the lip. The lateral nasal process forms the outer parts of the nose, and the maxillary process forms the bulk of the upper lip and the cheeks. (B redrawn from Ten Cate AR. Oral Histology. 3rd ed. St Louis: Mosby; 1989; C redrawn from Sulik KK, Johnston MC. Scan Elect Microsc 1:309-322, 1982.)
Clefting of the lip occurs because of a failure of fusion between the median and lateral nasal processes and the maxillary prominence, which normally occurs in humans during the sixth week of development. At least theoretically, a midline cleft of the upper lip could develop because of a split within the median nasal process, but this almost never occurs. Instead, clefts of the lip occur lateral to the midline on either or both sides (Figure 5-8). Since the fusion of these processes during primary palate formation creates not only the lip but the area of the alveolar ridge containing the central and lateral incisors, it is likely that a notch in the alveolar process will accompany a cleft lip even if there is no cleft of the secondary palate.
Closure of the secondary palate by elevation of the palatal shelves (Figures 5-9 and 5-10) follows that of the primary palate by nearly 2 weeks, which means that an interference with lip closure that still is present can also affect the palate. About 60% of individuals with a cleft lip also have a palatal cleft (Figure 5-11). An isolated cleft of the secondary palate is the result of a problem that arose after lip closure was completed. Incomplete fusion of the secondary palate produces a notch in its posterior extent (sometimes only a bifid uvula). This indicates a very late-appearing interference with fusion.
FIGURE 5-9 Scanning electron micrographs of mouse embryos sectioned in the frontal plane. A, Before elevation of the palatal shelves. B, Immediately after depression of the tongue and elevation of the shelves. (Courtesy Dr. K. Sulik.)
FIGURE 5-10 Scanning electron micrographs of the stages in palate closure (mouse embryos sectioned so that the lower jaw has been removed), analogous to the same stages in human embryos. A, At the completion of primary palate formation. B, Before elevation of the palatal shelves, equivalent to Figure 3-8, A. C, Shelves during elevation. D, Initial fusion of the shelves at a point about one third of the way back along their length. E, Secondary palate immediately after fusion. (Courtesy Dr. K. Sulik.)
The width of the mouth is determined by fusion of the maxillary and mandibular processes at their lateral extent, so a failure of fusion in this area could produce an exceptionally wide mouth, or macrostomia. Failure of fusion between the maxillary and lateral processes could produce an obliquely directed cleft of the face. Other patterns of facial clefts are possible, based on the details of fusion, and were classified by Tessier.6 Fortunately, these conditions are rare.
Morphogenetic movements of the tissues are a prominent part of the fourth stage of facial development. As these have become better understood, the way in which clefts of the lip and palate develop has been clarified. For example, it is known now that cigarette smoking by the mother is an etiologic factor in the development of cleft lip and palate,7 and even passive smoke increases the risk of cleft palate.8 An important initial step in development of the primary palate is a forward movement of the lateral nasal process, which positions it so that contact with the median nasal process is possible. The hypoxia associated with smoking probably interferes with this movement.
Another major group of craniofacial malformations arise considerably later than the ones discussed so far, during the final stage of facial development and in the early fetal rather than the embryologic period of prenatal life. These are the craniosynostosis syndromes, which result from early closure of the sutures between the cranial and facial bones. In fetal life, normal cranial and facial development depends on growth adjustments at the sutures in response to growth of the brain and facial soft tissues. Early closure of a suture, called synostosis, leads to characteristic distortions, depending on the location of the early fusion.9
Crouzon’s syndrome is the most frequently occurring member of this group. It is characterized by underdevelopment of the midface and eyes that seem to bulge from their sockets (Figure 5-12). This syndrome arises because of prenatal fusion of the superior and posterior sutures of the maxilla along the wall of the orbit. The premature fusion frequently extends posteriorly into the cranium, producing distortions of the cranial vault as well. If fusion in the orbital area prevents the maxilla from translating downward and forward, the result is severe underdevelopment of the middle third of the face. The characteristic protrusion of the eyes is largely an illusion—the eyes appear to bulge outward because the area beneath them is underdeveloped. There may be a component of true extrusion of the eyes, however, because when cranial sutures become synostosed, intracranial pressure increases.
FIGURE 5-12 A and B, Facial appearance in Crouzon’s syndrome of moderate severity, at age 8 years 8 months. Note the wide separation of the eyes (hypertelorism) and deficiency of the midfacial structures, both of which are characteristic of this syndrome. Because of premature suture fusion, forward development of the midface is retarded, which produces the apparent protrusion of the eyes.
Although the characteristic deformity is recognized at birth, the situation worsens as growth disturbances caused by the fused sutures continue postnatally. Surgery to release the sutures is necessary at an early age.
Intrauterine Molding: Pressure against the developing face prenatally can lead to distortion of rapidly growing areas. Strictly speaking, this is not a birth injury, but because the effects are noted at birth, it is considered in that category. On rare occasions, an arm is pressed across the face in utero, resulting in severe maxillary deficiency at birth (Figure 5-13). Occasionally, a fetus’ head is flexed tightly against the chest in utero, preventing the mandible from growing forward normally. This is related to a decreased volume of amniotic fluid, which can occur for any of several reasons. The result is an extremely small mandible at birth, usually accompanied by a cleft palate because the restriction on displacement of the mandible forces the tongue upward and prevents normal closure of the palatal shelves.
FIGURE 5-13 Midface deficiency in a 3-year-old still apparent though much improved from the severe deficiency that was present at birth because of intrauterine molding. Prior to birth, one arm was pressed across the face. (From Proffit WR, White RP, Sarver DM. Contemporary Treatment of Dentofacial Deformity. St. Louis: Mosby; 2003.)
This extreme mandibular deficiency at birth is termed the Pierre Robin anomalad or sequence. It is not a syndrome that has a defined cause; instead, multiple causes can lead to the same sequence of events that produce the deformity. The reduced volume of the oral cavity can lead to respiratory difficulty at birth, and it may be necessary to perform a tracheostomy so the infant can breathe. Early mandibular advancement via distraction osteogenesis has been used recently in these severely affected infants to provide more space for an airway so that the tracheostomy can be closed.
Because the pressure against the face that caused the growth problem would not be present after birth, there is the possibility of normal growth thereafter and perhaps eventually a complete recovery. Some children with Pierre Robin sequence at birth do have favorable mandibular growth in childhood, but a smaller than normal mandible typically persists (Figure 5-14), and a recent study found no catch-up growth during adolescence.10 It has been estimated that about one-third of the Pierre Robin patients have a defect in cartilage formation and can be said to have Stickler syndrome. Not surprisingly, this group has limited growth potential. Catch-up growth is most likely when the original problem was mechanical growth restriction that no longer existed after birth.
FIGURE 5-14 This girl was diagnosed at birth as having the Pierre Robin sequence, which results in a very small mandible, airway obstruction, and cleft palate. Some children with this condition have enough postnatal mandibular growth to largely correct the jaw deficiency, but the majority do not. At age 9, her mandibular deficiency persists. (From Proffit WR, White RP, Sarver DM. Contemporary Treatment of Dentofacial Deformity. St. Louis: Mosby; 2003.)
Birth Trauma to the Mandible: Many facial deformity patterns now known to result from other causes once were blamed on injuries during birth. Many parents, despite explanations from their doctors, will refer to their child’s facial deformity as being caused by a birth injury even if a congenital syndrome is evident. No matter what the parents say later, a recognizable syndrome obviously did not arise because of birth trauma.
In some difficult births, however, the use of forceps to the head to assist in delivery might damage either or both of the temporomandibular (TM) joints. At least in theory, heavy pressure in the area of the TM joints could cause internal hemorrhage, loss of tissue, and a subsequent underdevelopment of the mandible. At one time, this was a common explanation for mandibular deficiency. If the cartilage of the mandibular condyle were an important growth center, of course, the risk from damage to a presumably critical area would seem much greater. In light of the contemporary understanding that the condylar cartilage is not critical for proper growth of the mandible, it is not as easy to blame underdevelopment of the mandible on birth injuries. Children with deformities involving the mandible are much more likely to have a congenital syndrome.
A progressive deformity is one that steadily becomes worse, which, of course, indicates early treatment. These problems, fortunately, arise much less frequently than the severe but stable deformities that comprise most of the jaw problems encountered in children.
In the frequent falls and impacts of childhood, the condylar neck of the mandible is particularly vulnerable, and fractures of this area in childhood are relatively common. Fortunately, the condylar process tends to regenerate well after early fractures. The best human data suggest that about 75% of children with early fractures of the mandibular condylar process have normal mandibular growth afterward and therefore do not develop malocclusions that they would not have had in the absence of such trauma. Unilateral condylar fracture is much more frequent than bilateral fractures. It seems to be relatively common for a child to crash the bicycle, chip a tooth and fracture a condyle, cry a bit, and then continue to develop normally, complete with total regeneration of the condyle. Often, the diagnosis of condylar fracture was never made.
When a problem does arise following condylar fracture, it usually is asymmetric growth deficiency, with the injured side (or, in bilateral fractures, the more severely injured side) lagging behind (Figure 5-15). After an injury, if there is enough scarring around the TM joint to restrict translation of the condyle, so that the mandible cannot be pulled forward as much as the rest of the growing face, subsequent growth will be restricted.
FIGURE 5-15 Mandibular asymmetry in an 8-year-old boy caused by deficient growth on the affected side after fracture of the left condylar process, probably at age 2. For this patient, growth was normal despite the complete loss of the mandibular condyle until age 6, when an attachment of the condylar process to the underside of the zygomatic arch on the injured side began to restrict growth; then facial asymmetry developed rapidly. (From Proffit WR, White RP, Sarver DM. Contemporary Treatment of Dentofacial Deformity. St. Louis: Mosby; 2003.)
This concept is highly relevant to the management of condylar fractures in children. It suggests, and clinical experience confirms, that there would be little if any advantage from surgical open reduction of a condylar fracture in a child. The additional scarring produced by surgery could make things worse. The best therapy therefore is conservative management at the time of injury and early mobilization of the jaw to minimize any restriction on movement. If deficient growth is observed, however, early treatment is needed (see Chapter 12).
Although an old condylar fracture is the most likely cause of asymmetric mandibular deficiency in a child, other destructive processes that involve the TM joint, such as rheumatoid arthritis (Figure 5-16), or a congenital absence of tissue as in craniofacial microsomia also can produce this problem.
FIGURE 5-16 Rheumatoid arthritis is an uncommon cause of facial asymmetry, but in the polyarticular form of the disease (multiple joints affected), the temporomandibular (TM) joints often are involved, and asymmetry may develop as one side is affected more than the other. A, Facial appearance age 12, 2 years after the diagnosis of polyarticular rheumatoid arthritis. B, Posteroanterior (P-A) cephalometric radiograph, age 12. Note the jaw asymmetry.
The facial muscles can affect jaw growth in two ways. First, the formation of bone at the point of muscle attachments depends on the activity of the muscle; second, the musculature is an important part of the total soft tissue matrix whose growth normally carries the jaws downward and forward. Loss of part of the musculature is most likely to result from damage to the motor nerve (muscle atrophies when its motor nerve supply is lost). The result would be underdevelopment of that part of the face, with a deficiency of both soft and hard tissues (Figure 5-17).
FIGURE 5-17 Facial asymmetry in an 11-year-old boy whose masseter muscle was largely missing on the left side. The muscle is an important part of the total soft tissue matrix; in its absence growth of the mandible in the affected area also is deficient. A, Age 4. B, Age 11. C, Age 17 after surgery to advance the mandible more on the left than right side. The soft tissue deficiency from the missing musculature on the left side still is evident.
Excessive muscle contraction can restrict growth in much the same way as scarring after an injury. This effect is seen most clearly in torticollis, a twisting of the head caused by excessive tonic contraction of the neck muscles on one side (primarily the sternocleidomastoid) (Figure 5-18). The result is a facial asymmetry because of growth restriction on the affected side, which can be quite severe unless the contracted neck muscles are surgically detached at an early age.11 Conversely, a major decrease in tonic muscle activity (as in muscular dystrophy, some forms of cerebral palsy, and various muscle weakness syndromes) allows the mandible to drop downward away from the rest of the facial skeleton. The result is increased anterior face height, distortion of facial proportions and mandibular form, excessive eruption of the posterior teeth, narrowing of the maxillary arch, and anterior open bite (Figure 5-19).12
FIGURE 5-18 Facial asymmetry in a 6-year-old girl with torticollis. Excessive muscle contraction can restrict growth in a way analogous to scarring after an injury. Despite surgical release of the contracted neck muscles at age 1, moderate facial asymmetry developed in this case, and a second surgical release of the left sternocleidomastoid muscle was performed at age 7. Note that the asymmetry reflects deficient growth of the entire left side of the face, not just the mandible.
Occasionally, unilateral excessive growth of the mandible occurs in individuals who seem metabolically normal. Why this occurs is entirely unknown. It is most likely in girls between the ages of 15 and 20 but may occur as early as age 10 or as late as the early 30s in either sex. The condition formerly was called condylar hyperplasia, and proliferation of the condylar cartilage is a prominent aspect; however, because the body of the mandible also is affected (Figure 5-20), hemimandibular hypertrophy now is considered a more accurate descriptive term.13 The excessive growth may stop spontaneously, but in severe cases removal of the affected condyle and reconstruction of the area are necessary.
FIGURE 5-20 A, Facial asymmetry in this 21-year-old woman developed gradually in her late teens, after orthodontic treatment for dental crowding during which there was no sign of jaw asymmetry, due to excessive growth of the mandible on the right side. B, The dental occlusion shows an open bite on the affected right side, reflecting the vertical component of the excessive growth. C, Note the grossly enlarged mandibular condyle on the right side. Why this type of excessive but histologically normal growth occurs and why it is seen predominantly in females is unknown.
In acromegaly, which is caused by an anterior pituitary tumor that secretes excessive amounts of growth hormone, excessive growth of the mandible may occur, creating a skeletal Class III malocclusion in adult life (Figure 5-21). Often (but not always—sometimes the mandible is unaffected while hands and/or feet grow), mandibular growth accelerates again to the levels seen in the adolescent growth spurt, years after adolescent growth was completed.14 The condylar cartilage proliferates, but it is difficult to be sure whether this is the cause of the mandibular growth or merely accompanies it. Although the excessive growth stops when the tumor is removed or irradiated, the skeletal deformity persists and orthognathic surgery to reposition the mandible is likely to be necessary (see Chapter 19).
FIGURE 5-21 Profile view (A) and cephalometric radiograph (B) of a 32-year-old man with acromegaly, which was diagnosed 3 years previously when he went to a dentist because his lower jaw was moving forward. After irradiation of the anterior pituitary area, growth hormone levels dropped and mandibular growth ceased. Note the enlargement of sella turcica and loss of bony definition of its bony outline, reflecting the secretory tumor in that location. (From Proffit WR, White RP,/>