14
Teeth
Rena N. D’Souza, Hitesh Kapadia, and Alexandre R. Vieira
T he presence of a complete and functional dentition is critical
to the overall health and well-being of an individual. In fact, the
size, shape, color, and alignment of teeth are determining charac-
teristics of facial expression and impart uniqueness to each human.
Individuals who lack a full complement of teeth as a result of disease,
trauma, or genetic disorders often endure emotional hardship due
to compromised facial aesthetics. Costly and sometimes complex
dental care is needed to restore normal structure and function to
dentition. Since teeth are critical for the proper mastication of
complex food substances, inefficient grinding compromises diges-
tion by salivary enzymes and may result in digestive problems. As
seen in older individuals who have lost teeth to periodontal disease
or dental caries, speech is often affected, as is vertical dimension and
facial aesthetics.
Anthropologists and paleontologists rely on the importance
of teeth in evolution because they are the best-preserved organs in
fossils. In fact, studies of fossilized teeth have revealed much about
the behavior and feeding habits of humans and their ancestors.
The presence of enamel, the hardest substance in the human body,
on the crowns of teeth makes them indestructible and valuable
resources for forensics. For developmental biologists, the forming
tooth organ is a useful paradigm for organogenesis, offering a
means to study how shape, size, and position are determined and
how specialized mineralized tissues are formed. Notwithstanding
these critical functions, the importance and uniqueness of teeth
are frequently overlooked by health professionals. This chapter
reviews the physical and histologic features of normal dentition
and describes classic and modern literature about the cellular and
molecular processes that result in a fully formed tooth. As a
logical progression, disorders that affect the patterning of denti-
tion, in particular those involving changes in the number, size,
and shape of teeth, will be outlined. This will be followed by an
overview of disorders that affect the mineralized matrices of teeth,
namely enamel, dentin, and cementum. Since the development of
dentition is not complete until teeth emerge from within their
bony crypts into the oral cavity, it is justifiable to include a section
on normal and abnormal tooth eruption.
The authors acknowledge the important contribution of Ronald J. Jorgenson to the
first edition of this text, which provided the basis for this chapter.
During the past decade, several advances in understanding
the molecular biology and genetics of tooth development have
been made and genes that are responsible for the major disorders
of dentition have been identified.
General Description
In humans, teeth represent approximately 20–25% of the total
surface area of the oral cavity or mouth. In contrast to the
monophyodont dentition present in rodents, human dentition is a
succedaneous dentition with two sets of teeth: a deciduous set that
predominates from ages 6 months to 6 years and a permanent set
that predominates from age 12 years onward. Between ages 6 and
12 years, teeth of both sets can be present and the dentition is said
to be mixed. The word deciduous refers to the fact that the teeth
exfoliate with time; primary is an acceptable alternative to decid-
uous and indicates the sequence of eruption. The word permanent
refers to the lifelong status of the ‘‘adult’’ teeth. An acceptable
alternative is secondary to reflect their place in the sequence.
Teeth are described in terms that reflect their position, func-
tion, or morphology (Fig. 14-1). The shape of each tooth is closely
adapted to its function. The incisors are shovel-shaped with thin,
flat edges that are used for biting or incising. The canines are used
for tearing tough food. The premolars with their sharp cusps are
used for shredding. The molars, each with four to five flat cusps, are
used for grinding the shredded food passed backward from the
premolars.
For heterodont mammalian dentition, the general dental
formula in each quadrant is three incisors, one canine, four pre-
molars, and three molars. In humans, one incisor and two pre-
molars have been lost, while rodents have lost two incisors, the
canine and premolars.1 There are 20 deciduous teeth and 32 per-
manent teeth (Fig. 14-1). The deciduous complement consists of
two incisors, one canine, and two molars in each quadrant (a
quadrant is half an arch). The permanent complement consists of
two incisors, one canine, two premolars, and three molars in each
quadrant. In ordinary circumstances, the deciduous teeth are
smaller than permanent teeth that will eventually replace them and
are consequently widely spaced. Permanent teeth that replace de-
ciduous teeth are said to be succedaneous (ensuing): the premolars
succeed the deciduous molars; the permanent molars, having no
predecessors, are correctly termed nonsuccedaneous teeth.
425
426 Craniofacial Structures
Fig. 14-1. Orientation of teeth in dental arches.
Patterning of Dentition
From an evolutionary genetic standpoint, mammalian dentition
is considered a segmental or sequentially arranged organ system
whose members are arrayed in specific number and in regionally
differentiated locations along the linear axes of the jaws.2 For
developmental biologists, the model of tooth development offers a
useful paradigm for studying patterning and morphogenesis or
the determination of position, size, shape, and number. Much of our
understanding about the patterning of dentition comes from mouse
studies. The use of transgenesis, gene targeting, expression analyses,
and functional in vivo and in vitro tooth recombinations as well as
bead implantation assays has greatly increased our understanding
about the molecular mechanisms that influence the patterning of
murine dentition.
While there is good left–right symmetry in human dentition,
anterior–posterior and buccal–lingual symmetries are highly var-
ied, suggesting a patterning gradient along these axes. Two the-
ories have been proposed to explain the patterning of dentition.
The field theory assumes that all tooth primordia are initially
identical and that varying concentrations of chemical morphogens
create gradients of patterning in different regions of the jaws. The
finding of an anterior–posterior (A–P) gradient of retinoic acid
concentration in the developing murine mandible lends some
support to the field theory.3 An alternate theory, the clone model,
proposes that each family of teeth arises from a distinct group of
neural crest stem cells that retain positional identity as they migrate
to the arches.4 The role of Hox genes in controlling positional
information along the A–P axis in Drosophila and other vertebrates
has lent credibility to the clone theory.5 Furthermore, it has been
shown that the final position of odontogenic mesenchyme in the
maxilla and mandible is determined by the original position of
these cells in the neural crest as well as the time when the cells
migrate out of the crest, thus supporting the clone theory over the
field theory.6 As will be evident from the following discussion on
tooth agenesis, it is unclear which of the two theories explains some
of the more consistent patterns of human tooth agenesis. For ex-
ample, missing lateral incisors are often associated with second
premolar agenesis, suggesting that teeth that are last to develop in a
given morphogenetic field may fall below a developmental thresh-
old. Alternatively, the observations that point to mutations in two
independent genes, MSX1 and PAX9, which both dominantly affect
premolar and molar formation, suggests that each tooth family or
‘‘clone’’ may require a different genetic code or combination of
genes during development. This selectivity may be best explained
by the clone theory.
Parts of Teeth
Teeth are composed of crowns and roots. The crowns comprise the
exposed portions of the teeth and are covered by enamel. Under the
enamel is a thick layer of dentin and a soft central core, the pulp
chamber. The terminology used to identify different surfaces and
structural components of teeth is described in Fig. 14-2.
Enamel is the hardest calcified structure in vertebrates and
covers the crowns of the teeth. It varies from 2 to 3 mm in thickness
over the bulkiest parts of the cusp to a knife-edge thickness at the
cementoenamel junction. Because enamel is acellular, it is nonvital
and cannot regenerate except by superficial remineralization. The
latter happens as a result of an exchange of mineral ions that occurs
on the surface of enamel. Enamel varies from translucent to yellow-
grey in color, but most of the hue of enamel-covered crowns is the
result of the dentin being visible through the enamel. Teeth that
have a thin layer of enamel appear more yellow, to reflect the color
of dentin. This is common in individuals of Asian descent.
Enamel formation is described conceptually as occurring in
three phases. The secretory phase is marked by the deposition of
an organic matrix by ameloblasts. At this stage, these cells are
called presecretory and secretory ameloblasts. They are elongated
cells that show nuclear polarity and secretory organelles.7,8 In the
second phase of mineralization, nucleation or crystal formation
occurs. As crystals elongate the final phase of maturation of en-
amel matrix occurs. At this stage, the organic matrix, in particular
amelogenin, is degraded by proteinases. The degradative products
of amelogenins are reabsorbed back into the ameloblasts.9,10
The principal classes of enamel matrix proteins are amelogenin,
ameloblastin, enamel, tuftelin, a metalloproteinase called enamely-
sin (MMP-20), a serine proteinase called enamel matrix serine
proteinase 1 (EMPSP1), and traces of dentin sialophosphoprotein
(DSPP). As will be discussed later, enamel malformations involve
mutations in genes that encode some of these matrix proteins.11
The major constituents of enamel are rods, rod sheaths, and
an interrod substance. The rods consist of networks of organic
particles around which apatite crystals are coalesced. Each rod is
surrounded by a sheath that is less highly calcified than the rod
proper. The nature of the interrod structure is not well-known,
although it is well-accepted that this area of enamel facilitates the
spread of dental caries toward dentin.8,12
The dentin constitutes the bulk of the tooth. It is a living
tissue that has many of the physical and chemical properties of
Fig. 14-2. Component parts of teeth.
 Teeth
bone. The dentin is yellow in color and far less brittle than the
enamel. The formation of dentin follows the same principles that
guide the formation of other hard connective tissues in the body,
namely cementum and bone. The first requirement is the presence
of highly specialized cells that can synthesize and secrete a highly
specialized organic matrix that is capable of accepting biologic
apatite or mineral.13 Other prerequisites include a rich vascular
supply and high levels of the enzyme alkaline phosphatase. Dentin-
forming cells or odontoblasts begin to secrete a predentin extra-
cellular matrix (ECM). They retreat in a pulpal direction but
remain connected to the matrix as it is being formed through cell
extensions called odontoblastic processes. The organic predentin
matrix is converted into a mineralized layer of dentin through a
highly complex process that begins some distance away from the
odontoblastic cell bodies. The outermost layer of dentin, which is
the first layer to be formed, is the mantle dentin; the remainder is
the circumpulpal dentin.14,15
Excellent reviews by Linde and Goldberg16 and Butler and
Ritchie17 detail the composition of dentin matrix and the process
of dentinogenesis. The organic phase of dentin is composed of
proteins, proteoglycans, lipids, various growth factors, and water.
Among the proteins, collagen is the most abundant and offers a
fibrous matrix for the deposition of carbonate apatite crystals. The
collagens that are found in dentin are primarily type I collagen
with trace amounts of type V collagen and some type I collagen
trimer. The importance of type I collagen as a key structural
component of dentin matrix is illustrated by the inherited dentin
disorder called dentinogenesis imperfecta (DGI) that is discussed
later in this chapter.
An important class of dentin matrix proteins is the non-
collagenous proteins (NCPs).17 The dentin-specific NCPs are den-
tin phosphoproteins (DPP) or phosphophoryns and dentin
sialoprotein (DSP). After type I collagen, DPP is the next most
abundant of dentin matrix proteins and represents almost 50% of
the dentin ECM. DPP is a polyionic macromolecule that is rich in
phosphoserine and aspartic acid. Its high affinity for type I col-
lagen as well as calcium makes it a strong candidate for the ini-
tiation of dentin mineralization. DSP accounts for 5–8% of the
dentin matrix and has a relatively high sialic acid and carbohy-
drate content. Its role in dentin mineralization is unclear at the
present time. For several years it was believed that DSP and DPP
were two independent proteins encoded by different genes. DPP
and DSP are specific cleavage products of a larger precursor
protein that was translated from one large transcript.18 This single
gene encoding for DSP and DPP is named dentin sialophos-
phoprotein (DSPP).
The importance of DSPP in dentin formation was recently
underscored with the discovery that mutations in this gene are
responsible for the underlying dentinal defects seen in dentino-
genesis imperfecta (DGI).19,20 The DGI locus maps to human
chromosome 4 within q13-21 where several other dentin ECM
genes reside. A second category of NCPs with Ca-binding
properties is classified as mineralized tissue-specific because they
are found in all the calcified connective tissues, namely dentin,
bone, and cementum. These include osteocalcin (OC) and bone
sialoprotein (BSP). A serine-rich phosphoprotein called dentin
matrix protein 1 (Dmp-1), whose expression was first described
as being restricted to odontoblasts,21 was later shown to be ex-
pressed by osteoblasts and cementoblasts22,23 and by brain cells.
Other NCPs in this group include osteopontin (OP) and os-
teonectin (SPARC). The fourth category of dentin NCPs is not
expressed in odontoblasts but is primarily synthesized in the liver
427
and released into the circulation. An example of a serum-borne
protein is a2HS-glycoprotein. Diffusible growth factors that ap-
pear to be sequestered within dentin matrix constitute the fifth
group of dentin NCPs. This group includes the bone morpho-
genetic proteins (BMP), insulinlike growth factors (IGF), and
transforming growth factor beta (TGF-b).24
The pulp occupies the pulp chamber (the core of the crown)
and the root canals. The incisal or occlusal surface of the pulp
chamber is the roof. Projections along the mesial and distal aspects
of the roof are the pulp horns. The apical surface of the pulp
chamber is the floor and serves as the exit point for the nerves and
vessels that traverse the root canals. Blood and lymph vessels are
found in the pulp, as are sensory and motor nerves. The only
sensation the pulp is able to transmit is pain. The bulk of the pulpal
tissue is a loose connective tissue that contains cells of many types,
fibroblasts, and the odontoblasts. Somatic stem cells from the
dental pulp of a deciduous molar are capable of regenerating sev-
eral tissues when transplanted in vivo.
Cementum is another calcified tissue of mesodermal origin.
The cementum covering the apical third of the root is cellular
(contains cementocytes), while that of the remaining two-thirds is
acellular. Cementum is less resorptive than bone, a fact that un-
doubtedly is related to its role in anchoring teeth and allowing
teeth to move through bone during eruption.
Development of Teeth
Teeth develop in distinct stages that are easily recognizable at the
microscopic level. Hence, stages in odontogenesis are described in
classic terms by the histologic appearance of the tooth organ.
From early to late, these stages are described as the lamina, bud,
cap, and bell (early and late) stages of tooth development.25,26
Recent advances made in the understanding of the molecular
control of tooth development have led to the development of new
terminology to describe tooth development as occurring in four
phases: initiation, morphogenesis, cell or cytodifferentiation, and
matrix apposition (Fig. 14-3).
The dental lamina marks the first morphologic sign of the
initiation of tooth development and is visible around 5 weeks of
human development. At this stage, cells in the dental epithelium
and underlying ectomesenchyme are dividing at different rates,
the latter more rapidly. The inductive influence of the dental
lamina to dictate the fate of the underlying ectomesenchyme has
been confirmed by several researchers.27
The bud stage is characterized by the continual growth of
cells of the dental lamina and ectomesenchyme. The latter is
condensed and termed the dental papilla. At this stage, the in-
ductive or tooth-forming potential is transferred from the dental
epithelium to the dental papilla. The transition from the bud to
the cap stage is an important step in tooth development because it
marks the onset of crown formation. The tooth bud assumes the
shape of a cap that is surrounded by the dental papilla. The ec-
todermal compartment of the tooth organ is referred to as the
dental or enamel organ. The enamel organ and dental papilla
become encapsulated by another layer of mesenchymal cells called
the dental follicle that separate the tooth organ papilla from the
other connective tissues of the jaws. A cluster of cells called the
enamel knot is an important organizing center within the dental
organ and is important for the formation of cusps.28,29 The en-
amel knot expresses a unique set of signaling molecules that in-
fluence the shape of the crown as well as the development of the
dental papilla. Similar to the fate of signaling centers in other
organizing tissues like the developing limb bud, the enamel knot
428 Craniofacial Structures
Fig. 14-3. Signaling in tooth development. Schematic description
of the diffusible signals and transcription factors involved in epithelial-
mesenchymal interactions during mouse tooth development. Growth
factors and morphogens involved are the bone morphogenetic proteins
(BMP), fibroblast growth factors (FGF), Sonic hedgehog (SHH), and
undergoes programmed cell death or apoptosis after cuspal pat-
terning is completed at the onset of the early bell stage.
The dental organ next assumes the shape of a bell as cells
continue to divide but at differential rates. A single layer of cu-
boidal cells called the external or outer dental epithelium lines the
periphery of the dental organ, while cells that border the dental
papilla and are columnar in appearance form the internal or inner
dental epithelium. The latter gives rise to the ameloblasts, cells
responsible for enamel formation. Cells located in the center of
the dental organ produce high levels of glycosaminoglycans that
are able to sequester fluids as well as growth factors that lead to its
expansion. This network of star-shaped cells is named the stellate
reticulum. Interposed between the stellate reticulum and the in-
ternal dental epithelium is a narrow layer of flattened cells, termed
the stratum intermedium, that express high levels of alkaline
phosphatase. The stratum intermedium is believed to influence
the biomineralization of enamel. In the region of the apical end of
the tooth organ, the internal and external dental epithelial layers
meet at a junction called the cervical loop.
At the early bell stage, each layer of the dental organ has as-
sumed special functions and exchanges molecular information that
leads to cell differentiation at the late bell stage. The dental lamina
that connects the tooth organ to the oral epithelium gradually
disintegrates at the late bell stage. At the future cusp tips, cells of the
internal dental epithelium stop dividing and assume a columnar
shape. The most peripheral cells of the dental papilla organize along
the basement membrane and differentiate into odontoblasts, the
Wingless protein (WNT). Several molecules function throughout
odontogenesis. In humans, mutations in PITX2, SHH, MSX1,
and PAX9 have been associated with Rieger syndrome, solitary median
maxillary central incisor, premolar/third molar agenesis, and molar
oligodontia, respectively. (Reprinted with permission from Thesleff.33)
dentin-forming cells. At this time, the dental papilla is termed the
dental pulp. After the first layer of predentin matrix is deposited,
cells of the internal dental epithelium differentiate into ameloblasts
or enamel-producing cells. As enamel is deposited over dentin
matrix, ameloblasts retreat to the external surface of the crown and
are believed to undergo programmed cell death. In contrast,
odontoblasts line the inner surface of dentin and remain meta-
bolically active throughout the life of a tooth. Root formation then
proceeds as epithelial cells proliferate apically and influence the
differentiation of odontoblasts from the dental papilla as well as
cementoblasts from follicle mesenchyme. This leads to the depo-
sition of root dentin and cementum, respectively. In multirooted
teeth, certain portions of the root sheath grow more rapidly than
the remainder, producing tonguelike extensions. When the exten-
sions (two in two-rooted and three in three-rooted teeth) meet, the
position of the root furcation is established. The dental follicle that
gives rise to components of the periodontium, namely the peri-
odontal ligament fibroblasts, alveolar bone of the tooth socket, and
the cementum, also plays a role during tooth eruption, which
marks the end phase of odontogenesis.
In summary, tooth development is regulated by temporally
and spatially restricted, reciprocal interactions between epithelial
and mesenchymal compartments, and the potential to dominate
tooth development shifts back and forth between epithelium and
mesenchyme.
The chronology of human tooth development is summarized
in Tables 14-1 A and B.
 Teeth 429

Table 14-1A. Developmental chart of deciduous teeth34

Calcification
Initiation Begins Crown Formation Crown Eruption Exfoliation
Tooth (wk in utero) (wk in utero) at Birth (38–42 wk) Complete (mo) (mo) (yr)

Lower central incisor 6–7 13–16 3/5 1–3 6–10 5–6

Lower lateral incisor 7 14–16 3/5 2–3 10–16 6–7
Upper incisors 7 14–16 5/6 central 2–3 8–13 6–7
2/3 lateral
Canines 7.5 15–18 1/3 9 16–20 9–10
First molars 8 14.5–17 Cusps united, occlusal surface 6 12–16 10–11
complete, 1/2–3/4 crown height
Second molars 10 16–23 Cusps united, 1/4 crown height 10–12 23–30 12

Table 14-1B. Developmental chart of permanent teeth34

Crown
Calcification complete Eruption
Initiation begins (yr) (yr)

Mandible

Central incisor 20–22 wk IU 3–4 mo 4–5 6–7

Lateral incisor 21–22 wk IU 3–4 mo 4–5 7–8

Canine 20–26 wk IU 4–5 mo 6–7 9–11
First premolar 38–42 wk IU 1.75–2 yr 5–6 10–12
Second premolar 7.5–8 mo 2.25–2.5 yr 6–7 11–12
First molar 15–17 wk IU Birth 2.5–3 6–7
Second molar 8.5–9 mo 2.5–3 yr 7–8 11–13
Third molar 3.5–4 yr 8–10 yr 12–16 17–25

Maxilla

Central incisor 20–22 wk IU 3–4 mo 4–5 7–8

Lateral incisor 21–22 wk IU 3–4 mo 4–5 8–9
Canine 21–26 wk IU 4–5 mo 6–7 11–12
First premolar 38–42 wk IU 1.25–1.75 yr 5–6 10–11
Second premolar 7.25–8 mo 2–2.5 yr 6–7 10–12
First molar 3.5–4 wk IU Birth 2.5–3 6–7
Second molar 8.5–9 mo 2.5–3 yr 7–8 12–13
Third molar 3.5–4 yr 7–9 yr 12–16 17–25

IU ¼ in utero.

In recent years significant advances have been made in under-
standing the molecular mechanisms that determine the site of tooth
initiation.30,31 Fig. 14-3 shows that a number of transcription factors,
signaling molecules (i.e., growth factors and their receptors), and
extracellular matrix molecules are expressed in the mesenchyme of
the first branchial arch. Several lines of evidence indicate that syn-
ergistic and antagonistic interactions of signaling molecules are re-
cursively utilized in tooth development.30–32
Clinical Considerations
Congenital malformations of the teeth can be more clearly under-
stood by considering tooth development in stages of initiation and
proliferation, morphogenesis, and matrix apposition. The dental
lamina initiates tooth development. If the lamina is not formed or its
early organization is abnormal, initiation will not occur and teeth
will not develop at all (anodontia). If only portions of the lamina are
physically disrupted, initiation is disrupted in focal areas and only
teeth in that area will not develop (hypodontia). Of course, some
disruptive factors may cause overactivity of the lamina, resulting in
hyperdontia (supernumerary teeth). After initiation, the separate
tooth buds proliferate at their predetermined paces. Interference
with proliferation also leads to hypodontia.
Histodifferentiation follows the initial steps of proliferation. Cell
types (ameloblasts and odontoblasts, for instance) are established
during the histodifferentiation stage. If the inner dental epithelium
does not differentiate properly, it cannot stimulate odontoblast for-
mation, and tooth development will be arrested. If odontoblasts fail
to differentiate properly, they cannot stimulate ameloblast formation
and no enamel will form. Abnormal dental structure, poorly orga-
nized and formed, results from abnormal differentiation.
Differential growth of parts of the dental organ (morpho-
differentiation) accounts for the basic size and shape of teeth.
430 Craniofacial Structures
Abnormal morphodifferentiation leads to microdontia, macro-
dontia, globodontia, supernumerary cusps, and other abnormalities.
Apposition refers to the deposition of the matrix of dentin
and enamel. Once the cells of the inner dental epithelium have
stimulated the underlying mesenchyme to form odontoblasts, the
odontoblasts lay down a layer of predentin. Mineralization begins
after sufficient predentin is present. The various types of dentin
dysplasia are probably defects of predentin deposition. After a small
amount of predentin has formed, ameloblasts begin to secrete the
enamel matrix and continue to do so until the predetermined size
of the crown has been reached. Too little enamel matrix leads to
hypoplastic types of enamel dysplasia. After the enamel matrix is
laid down, it is mineralized; disruptions at this stage of develop-
ment lead to hypocalcified types of enamel dysplasia. Maturation of
the hard matrix follows appositional growth. Interference with
maturation leads to such manifestations as hypomature forms of
enamel dysplasia.
Future Challenges and Directions
The molecular basis for malformations of human teeth is beginning
to be delineated; however, there remains much to be resolved in the
area of genotype-phenotype correlations. How locus-specific mu-
tations affect phenotypic changes as measured by tooth shape,
position, size, and number is poorly understood. The availability of
improved dental diagnostic and genomic tools along with sophis-
ticated mouse transgenesis will greatly add to our knowledge of how
allele-specific alterations influence patterns of inheritable disease.
Although tooth malformations compromise emotional well-
being and impose significant financial burdens on patients and
their families, these conditions are not life threatening. Therefore,
the identification and diagnosis of multigenerational families seg-
regating disorders affecting dentition offers an exciting avenue for
research on the genetic etiology of dental diseases. The legacy of
inheritable anomalies of human dentition will continue to provide
a unique and powerful system for studying the genetic pathways
that control the development of human dentition. Knowledge
about normal and abnormal tooth development and eruption is
essential in the postgenomic area as emerging technologies of
biomimetics and tissue engineering are applied to the field of re-
generative dental medicine. The next decade will benefit from these
advances as they can be well-applied to the bioengineering of an-
imal and human tooth structures through the use of either em-
bryonic or adult (somatic) stem cells. These multipotential cells can
be derived from bone marrow stroma as well as from tissues de-
rived from individual layers of embryonic tooth organs or the in-
tact tooth germ itself.35–37 Stem cell populations existent in
deciduous teeth that are shed have also shown the potential to form
mineralized tooth structures like dentin and bone and to regenerate
nerve tissues as well.38–40
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dentin matrix acidic phosphoprotein. Implications for induction of
biomineralization. J Biol Chem 268:12624, 1993.
22. D’Souza RN, Cavender A, Sunavala G, et al.: Gene expression patterns
of murine dentin matrix protein 1 (Dmp1) and dentin sialophospho-
protein (DSPP) suggest distinct developmental functions in vivo.
J Bone Miner Res 12:2040, 1997.
23. Hirst KL, Simmons D, Feng J, et al.: Elucidation of the sequence and the
genomic organization of the human dentin matrix acidic phosphopro-
tein 1 (DMP1) gene: exclusion of the locus from a causative role in the
pathogenesis of dentinogenesis imperfecta type II. Genomics 42:38,
1997.
24. Smith AJ, Lesot H: Induction and regulation of crown dentinogenesis:
embryonic events as a template for dental tissue repair? Crit Rev Oral
Biol Med 12:425, 2001.
25. Ten Cate AR: Oral Histology: Development, Structure, and Function,
ed 5. Mosby, St. Louis, 1998.
26. Avery JK: Oral Development and Histology. Mosby Year Book,
St. Louis, 1987.
27. Mina M, Kollar EJ: The induction of odontogenesis in non-dental
mesenchyme combined with early murine mandibular arch epithe-
lium. Arch Oral Biol 32:123, 1987.
28. Jernvall J, Kettunen P, Karavanova I, et al.: Evidence for the role of the
enamel knot as a control center in mammalian tooth cusp formation:
non-dividing cells express growth stimulating Fgf-4 gene. Int J Dev
Biol 38:463, 1994.
29. Jernvall J, Aberg T, Kettunen P, et al.: The life history of an embryonic
signaling center: BMP-4 induces p21 and is associated with apoptosis
in the mouse tooth enamel knot. Development 125:161, 1998.
 Teeth
30. Peters H, Balling R: Teeth. Where and how to make them. Trends
Genet 15:59, 1999.
31. Jernvall J, Thesleff I: Reiterative signaling and patterning during
mammalian tooth morphogenesis. Mech Dev 92:19, 2000.
32. Thesleff I: The genetic basis of normal and abnormal craniofacial
development. Acta Odontol Scand 56:321, 1998.
33. Thesleff I: Epithelial-mesenchymal signalling regulating tooth mor-
phogenesis. J Cell Science 116:1647, 2003.
34. Cameron AC, Widmer RP: Handbook of Paediatric Dentistry, ed 2.
Mosby, London, 1998, p 355–356.
35. Young CS, Terada S, Vacanti JP, et al.: Tissue engineering of complex
tooth structures on biodegradable polymer scaffolds. J Dent Res 81:695,
2002.
36. Duailibi MT, Duailibi SE, Young CS, et al.: Bioengineered teeth from
cultured rat tooth bud cells. J Dent Res 83:523, 2004.
37. Ohazama A, Modino SA, Miletich I, et al.: Stem-cell-based tissue
engineering of murine teeth. J Dent Res 83:518, 2004.
38. Gronthos S, Mankani M, Brahim J, et al.: Postnatal human dental pulp
stem cells (DPSCs) in vitro and in vivo. Proc Natl Acad Sci USA
97:13625, 2000.
39. Gronthos S, Brahim J, Li W, et al.: Stem cell properties of human
dental pulp stem cells. J Dent Res 81:531, 2002.
40. Miura M, Gronthos S, Zhao M, et al.: SHED: stem cells from human
exfoliated deciduous teeth. Proc Natl Acad Sci USA 100:5807, 2003.
14.1
Tooth Agenesis
Definition
Tooth agenesis is the congenital lack of one or more of the deciduous
or permanent teeth. It is classified as a clinically and genetically
heterogenous condition that affects specific groups of teeth. It is the
most common developmental anomaly in humans. The third mo-
lars, for instance, are congenitally absent so commonly that surveys
of tooth agenesis frequently exclude this tooth type for consider-
ation. The literature uses several terms to describe tooth agenesis that
are based on the number of teeth involved. Oligodontia is the
agenesis of six or more permanent teeth, whereas absence of less than
431
six teeth is referred as hypodontia. Anodontia refers to the absence of
all deciduous and permanent teeth (Fig. 14-4).
Diagnosis
A tooth is considered congenitally absent when it is not present
clinically (erupted) or radiographically (unerupted) at an age when
it is expected to be present. The extent to which tooth agenesis is
manifested varies widely and can be presented as the only pheno-
typic feature (isolated) or associated with other anomalies or as
part of a syndrome.
Among the several developmental anomalies involving human
dentition, the field of tooth agenesis has shown the most progress.
The genetic etiology of tooth agenesis has received much attention
in recent years, and as Tables 14-2 to 14-5 describe, several genes
and underlying mutations have been reported to cause tooth
agenesis.
Many of these discoveries have been guided by knowledge
about the genes involved in murine tooth development, in par-
ticular those that are important for the initiation of odontogenesis.
Etiology and Distribution
Tooth agenesis occurs more frequently among a few specific teeth
(lateral incisors, second premolars, and third molars), with 10–
25% of the population affected. Familial tooth agenesis is trans-
mitted as autosomal dominant, autosomal recessive, and X-linked
conditions but can also show no clear segregation pattern. Affected
members within a family often exhibit significant variability with
regard to the location, symmetry, and number of teeth involved.
Residual teeth can vary in size, shape, or rate of development. The
permanent dentition is more affected than the primary dentition.
Animal models suggest that specific genetic factors might be in-
volved with specific types of teeth during development. Mice with
targeted null mutations of both Dlx-1 and Dlx-2 homeobox genes
do not develop maxillary molar teeth, but the incisors and man-
dibular molars are normal. In contrast, among mice with mutant
activin ßA (a member of the transforming growth factor (TGF) ß
superfamily), incisors and mandibular molar teeth fail to develop
Fig. 14-4. Congenitally missing teeth.
Intraoral photographs and panoramic radio-
graphs from a normal 11-year-old male
individual (A,B,C) and his 19-year-old af-
fected brother, (D,E,F). A,B,C. Normal mixed
primary and permanent dentition. Note the
impacted maxillary central incisor and the
presence of permanent first and second molars
(arrows). Crowns shown in B were placed
on the primary molars after the radiograph
was taken. D,E,F. Affected individual with
the following anomalies: peg-shaped lateral
incisors; reduced mesiodistal widths and
conical shape of permanent teeth; overre-
tained primary second molars and mandibular
central incisors. Notably, permanent mandib-
ular central incisors and all permanent teeth
distal to the first premolars are congenitally
missing (solid arrows).
432 Craniofacial Structures

Table 14-2. Isolated tooth agenesis

Causation
Phenotype Gene/Locus

Hypodontia1 Polygenic Possibly MSX1, PAX9, TGFA, others

Hypodontia with anomalous shape of pulp AR (602639) 16q12.1
chambers and pulp canals2
Oligodontia with preferential agenesis of second Sporadic (106600) PAX9, 14q12–q13
premolars and third molars3
Oligodontia with preferential agenesis of second AD (106600)
premolars and third molars4,5 MSX1, 4p16.1
Oligodontia with preferential molar agenesis6–13 AD (106600)
PAX9, 14q12–q13
Oligodontia with preferential molar agenesis14 AD (106600)
MSX1, 4p16.1
Severe oligodontia including deciduous and AD (106600)
permanent molar agenesis8 PAX9, 14q12–q13

Table 14-3. Tooth agenesis associated with other defects teeth, deficient growth of the alveolar processes associated with the
or diseases missing teeth, and excess space within the dental arches. The
Causation availability of space results in drifting, tipping, and supraeruption
Phenotype Locus/Genes of the adjacent or opposing teeth. In molar oligodontia, the
functional atrophy in alveolar ridge height is easily recognizable.
Anodontia and strabismus15 AD, Unknown
Syndromic and nonsyndromic forms of tooth agenesis that involve
Asphyxiating thoracic dystrophy Chromosomal (208500) multiple teeth result in significant aesthetic, emotional, and fi-
and oligodontia16 Deletion, 12p11.21–p12.2
nancial burdens placed on families faced with the ordeal and costs
Cleft lip and palate and hypo-dontia Polygenic associated with restoring the dentitions of several affected family
outside the cleft area17 Possibly MSX1, TGFB3, others members. The average cost for the restoration of dentition in pa-
Coloboma of macula with type B Sporadic (120400) tients affected with severe forms of tooth agenesis approximates
brachydactyly and oligodontia18 $50,000 to $60,000 per individual. Although clinicians have long
Hypodontia and Dupuytren AD (126900) observed hypodontia and oligodontia, the early diagnosis, pre-
contracture19 with incomplete penetrance ventive or interceptive dental measures, and treatment options for
Leukodystrophy and oligodontia20 AR (607694) this condition have been extremely limited. The number and type
Medullary sponge kidney and AR of missing teeth as well as individual skeletal proportions and
anodontia of permanent dentition21 aesthetic considerations generally dictate treatment regimens.
Oligodontia and colorectal cancer22 AD Therapy is phasic, complicated, and lengthy, involving at least two
AXIN2 dental specialists. Orthodontic appliances are ideal for the re-
Oligodontia and congenital AR (221740)
positioning of existing teeth and the consolidation of space for
sensorineural hearing loss23,24 either a fixed or removable prosthesis. However, when several teeth
are missing, as seen in molar oligodontia, orthodontic correction is
Oligodontia and polycystic ovaries25 AR
followed by bone augmentation procedures to increase the bone
mass prior to the placement of implants. With the exception of
syndromic cases of anodontia, molar oligodontia presents with the
most severe of dental complications.
beyond a rudimentary bud, whereas maxillary molar teeth develop There are no useful preventive measures for tooth agenesis,
normally. The mice lack whiskers and have defects in the secondary and prenatal diagnosis is impossible or considered by many to be
palates, including cleft palate. In humans, mutations in MSX1 and unwarranted. In theory, anodontia can be detected prenatally by
PAX9 have been associated with tooth agenesis, but those muta- ultrasound examination. It is doubtful that a couple would choose
tions probably cause only a very few cases. However, the pattern of to modify the course of a pregnancy for isolated anodontia,
tooth agenesis from these mutations is remarkable, with PAX9 making prevention a moot point.
causing preferential agenesis of molars and MSX1 causing prefer-
ential agenesis of second premolars and third molars. The majority References (Tooth Agenesis)
of the tooth agenesis cases are probably multifactorial with many
1. Vieira AR, Meira R, Modesto A, et al.: MSX1, PAX9, and TGFA
genes involved.206 Epidemiologic characteristics of tooth agenesis
contribute to tooth agenesis in humans. J Dent Res 83:723, 2004.
are listed in Table 14-6.
2. Ahmad W, Brancolini V, Ul Faiyaz MF, et al.: A locus for autosomal
Prognosis, Treatment, and Prevention recessive hypodontia with associated dental anomalies maps to chromo-
some 16q12.1. Am J Hum Genet 26:987, 1998.
Unless agenesis of one or more teeth is associated with a syndrome, 3. Mostowska A, Kobielak A, Biedziak B, et al.: Novel mutation in the
prognosis is good. The unavoidable dental consequences of tooth paired box sequence of PAX9 gene in a sporadic form of oligodontia.
agenesis include malocclusion due to improper position of the Eur J Oral Sci 111:272, 2003.
Table 14-4. Syndromes with tooth agenesis as a component
Syndrome
Autosomal Dominant Conditions
Acrofacial dysostosis, type Nager26,27
Acrofacial dysostosis, type Palagonia28
Adenomatous polyposis of the colon29,30
ADULT31–33
Alagille34,35
Ankyloplepharon-ectodermal
defects-cleft lip/palate36,37
Axenfeld-Rieger38–43
Book44
Branchio-oculo-facial45
Choanal atresia with maxillary
hypoplasia, prognathism,
and hypodontia46
Ectodermal dysplasia 347,48
Ectrodactyly-ectodermal
dysplasia-clefting49–51
Ehlers-Danlos type VI52–54
Causation
Prominent Features Locus/Gene
Limb deformities, severe micrognathia (154400)
and malar hypoplasia (can also 9q32, 1q12–q21
be autosomal recessive)
Oligodontia, short stature, frizzy (601829)
hair with aplasia cutis verticis,
hand anomalies, unilateral cleft
lip, some vertebral anomalies
(can also be X-linked dominant)
Adenomatous polyps of the colon (175100)
and rectum, congenital hypertrophy APC, 5q21-q22
of the retinal pigment epithelium,
dental anomalies
Ectrodactyly, syndactyly, nail dysplasia, (103295)
hypoplastic breasts and nipples, p63, 3q27
intensive freckling, lacrimal duct
atresia, frontal alopecia, primary
hypodontia, loss of permanent teeth
Eye anomalies, cardiovascular (118450)
anomalies, abnormal vertebrae, JAG1, 20p12
cognitive problems, typical facies,
hypodontia, oral xanthomas
Coarse, wiry, sparse hair; dystrophic (106260)
nails; slight hypohidrosis; scalp p63, 3q27
infections; ankyloblepharon
filiforme adnatum; hypodontia;
maxillary hypoplasia; cleft lip/palate
Eye, dental, and umbilical anomalies (180500)
PITX2, 4q25–q26
FOXC1, 6p25
13q14
Congenitally missing premolars, (112300)
narrow palate, severe functional
hyperhidrosis of the hands and
feet, small hands, hypoplastic nails
Branchial clefts with characteristic (113620)
facies, growth retardation,
imperforate nasolacrimal duct,
premature aging
Bilateral choanal atresia, tall forehead,
maxillary hypoplasia, prognathism,
hypodontia
Mild hypotrichosis, mild (129490)
hypodontia, and variable EDAR, 2q11–q13
degrees of hypohidrosis
(can also be autosomal recessive)
Lobster-claw anomalies of hands (129900)
and feet, lacrimal duct anomalies (EEC1) 7q11.2–q21.3
with ocular complications, (EEC2) 19p13–q13
cleft lip/palate (most (EEC3) p63, 3q27
cases are sporadic)
Ocular, muscular, and skin defects; (225400)
abnormal maxilla; occasional PLOD1, 1p36.3–p36.2
hypodontia and/or smaller teeth sizes
(continued)
433
 Table 14-4. Syndromes with tooth agenesis as a component (continued)

Causation
Syndrome Prominent Features Locus/Gene

Hair-nail-skin-teeth dysplasias55 Large number of rare disorders (125640, 257980,

Hallermann-Streiff56
Hypodontia with orofacial clefts57
Kallmann58,59
KBG60
LADD61
Limb-mammary62,63
Niikawa-Kuroki (Kabuki)64–66
Oculodentodigital dysplasia67,68
Oligodontia, microcephaly,
short stature, characteristic facies69
Otodental dysplasia70
Popliteal pterygium71,72
involving binary, ternary, or 262020, 272980, 275450)
quaternary combination of hair,
nails, skin appendages, and teeth
anomalies (can also be autosomal
recessive or X-linked)
Birdlike facies with hypoplastic (234100)
mandible and beaked nose,
proportionate dwarfism,
hypotrichosis, microphthalmia,
dental anomalies, congenital cataract
Cleft lip and palate, cleft palate (106600)
alone, oligodontia with MSX1, 4p16.1
preferential agenesis of second
premolars and third molars
Hypogonadotropic hypogonadism, (147950)
anosmia, bimanual synkinesia, FGFR1, 8p11.2–p11.1
cleft lip or palate, multiple
dental agenesis
Short stature, characteristic facies, (148050)
mental retardation, skeletal
anomalies, oligodontia, macrodontia
Aplasia or hypoplasia of the (149730)
puncta with obstruction of
the nasal lacrimal ducts; ear,
dental, and hand anomalies
Severe hand/foot anomalies and (603543)
hypoplasia/aplasia of the p63, 3q27
mammary gland and nipple,
lacrimal-duct atresia, nail
dysplasia, hypohidrosis,
hypodontia, cleft palate with or
without bifid uvula
A peculiar face, characterized by (147920)
eversion of the lower lateral
eyelid, arched eyebrows with
sparse or dispersed lateral one-
third, depressed nasal tip, and
prominent ears; skeletal anomalies,
dermatoglyphic abnormalities,
mild to moderate mental
retardation; postnatal growth
deficiency, heart defects,
dental anomalies
Bilateral microphthalmos, (164200)
abnormally small nose, GJA1, 6q21-q23.2
hypotrichosis, dental anomalies,
fifth finger camptodactyly,
syndactyly of the fourth and
fifth fingers, missing toe phalanges
Microcephaly, short stature, Unknown
characteristic facies, oligodontia
Sensorineural hearing loss, dental (166750)
anomalies, missing premolars
Cleft lip/palate, paramedian (119500)
mucous cysts of the lower IRF6, 1q32-q41
lip, webbing of the lower limbs,
digital and genital anomalies
(continued)

434
Table 14-4. Syndromes with tooth agenesis as a component (continued)

Causation
Syndrome Prominent Features Locus/Gene

Scalp-ear-nipple73 Abnormality of the scalp, ears, (181270)

nipples, tooth agenesis, and Unknown
renal anomalies
Shopf-Schulz-Passarge74,75 Keratosis palmoplantaris with (224750)
cystic eyelids, hypodontia, 17q24
hypotrichosis (can also be
autosomal recessive)
Ulnar-mammary76–78 Posterior (ulnar or postaxial) (181450)
limb deficiencies and/or TBX3, 12q24.1
duplications, mammary
gland hypoplasia, apocrine
dysfunction, and dental and
genital abnormalities
Uncombable hair, retinal pigmentary Congenital hypotrichosis, (191482)
dystrophy, dental anomalies, uncombable hair, associated
and brachydactyly79,80 with juvenile cataracts, retinal
pigmentary dystrophy,
oligodontia, and brachymetacarpy
Van der Woude71,72,81–84 Lip pits, cleft of lip/palate, (119300)
hypodontia IRF6, 1p34
Witkop (tooth-and-nail)85 Missing teeth and poorly (189500)
formed nails MSX1, 4p16.1

Autosomal Recessive Conditions

Agonadism, XY, with mental retardation,
short stature, retarded bone age, and
multiple extragenital malformations86
Amelogenesis imperfecta and platyspondyly87
Bardet-Biedl88–94
Blepharo-cheilodontic95
Brachymetapody-anodontia-hypotrichosis-albinoidism96
Cerebellar hypoplasia with endosteal sclerosis97
Cleft lip/palate, congenital contractures,
ectodermal dysplasia, and psychomotor
and growth retardation98
Cleft lip/palate-ectodermal dysplasia99,100
Minor anomalies: peculiar face, Unknown
hypodontia, short neck,
inverted nipples, thoracolumbar
scoliosis, ‘‘dysplastic’’ hips, partial
clinodactyly/syndactyly of the toes
Mild growth retardation, (601216)
platyspondyly, vertebral defects, Unknown
pectus carinatum, limited
extension at the elbows,
amelogenesis imperfecta, oligodontia
Mental retardation, pigmentary Multiple loci
retinopathy, polydactyly, obesity,
hypogenitalism
Cleft lip and/or palate, ectropion (119580)
of the lower eyelids with ocular
hypertelorism, and dental anomalies
Congenital anodontia, small maxilla, (211370)
short stature, little hair growth,
albinoidism, multiple ocular
abnormalities
Ataxia and developmental delay, (213002)
microcephaly, short stature,
oligodontia, strabismus, nystagmus,
congenital hip dislocation
Typical facies, congenital contractures, (301815)
orofacial clefts, oligodontia and other
teeth anomalies (may also be X-linked)
Anhidrosis, hypotrichosis, (225000)
dental anomalies, dysplasia PVRL1, 11q23–q24
of nails, cleft lip and palate,
deformity of the fingers and toes,
malformation in the genitourinary system,
popliteal perineal pterygium, syndactyly
(continued)

435
 Table 14-4. Syndromes with tooth agenesis as a component (continued)

Causation
Syndrome Prominent Features Locus/Gene

Cleft palate, stapes fixation, Cleft palate, stapes fixation, (216300)

and oligodontia101 oligodontia
Cockayne102–104 Dwarfism, precociously senile (216400)
appearance, pigmentary XPB, XPD, XPG, CSA, CSB
retinal degeneration, optic
atrophy, deafness,
disproportionately long limbs
with large hands and feet and
flexion contractures of joints,
marble epiphyses in some digits,
photosensitivity, mental retardation
Cranioectodermal dysplasia105 Dolichocephaly; sparse, slow-growing, (218330)
fine hair; epicanthal folds; hypodontia
and/or micro-dontia; brachydactyly;
narrow thorax
Dermatoosteolysis, Kirghizian type106 Recurrent skin ulceration, arthralgia, (221810)
fever, fistulous osteolysis around
joints, oligodontia, nail dystrophy,
keratitis with visual impairment
or blindness
Dysosteosclerosis107 Anterior fontanel tends to remain (224300)
open, oligo-dontia, progressive
mental retardation, oto-sclerosis,
intracerebral calcifications (can
also be X-linked)
Ectodermal dysplasia, Scanty eyebrows and eyelashes; (225060)
Margarita Island type100,108 sparse, short, and dry scalp hair; PVRL1, 11q23-q24
dental anomalies; cleft lip/palate;
syndactyly of fingers and toes;
onychodysplasia
Ellis-van Creveld109–111 Skeletal dysplasia characterized by (225500)
short limbs, short ribs, postaxial EVC, EVC2
polydactyly, dysplastic
nails and teeth
Epidermolysis bullosa112–116 Dystrophy of the nails, nonscarring (226650)
blistering of skin, mild skin atrophy, COL17A1, LAMA3,
hypodontia LAMB3, LAMC2, ITGB4
Gorlin-Chaudhry-Moss117 Craniofacial dysostosis, hypertrichosis, (233500)
hypoplasia of labia majora, dental
and eye anomalies, patent ductus
arteriosus, normal intelligence
Hanhart118–120 Aglossia, adactylia; is often associated (103300)
with missing mandibular incisors,
hypertrophy of salivary glands
(most cases are sporadic)
Hennekan lymphangiectasia-lymphedema121 Intestinal lymphangiectasia with severe (235510)
lymphedema of the limbs, genitalia,
and face; severe mental retardation;
facial anomalies
Johanson-Blizzard122 Aplasia or hypoplasia of the nasal alae, (243800)
congenital deafness, hypothyroidism,
postnatal growth retardation, mental
retardation, midline ectodermal scalp
defects, microdontia or absent
permanent teeth
Leukomelanoderma, infantilism, mental Mental retardation, (246500)
retardation, hypodontia, hypotrichosis123 leukomelanoderma,
hypotrichosis, hypodontia
(continued)

436
Table 14-4. Syndromes with tooth agenesis as a component (continued)
Syndrome
MULIBREY nanism124,125
Odontotrichomelic126
Polydactyly, postaxial, with dental
and vertebral anomalies127
Progeria128,129
Pycnodysostosis130
Richieri-Costa and Pereira131
Rothmund-Thomson132,133
Spondyloepimeta-physeal dysplasia
with abnormal dentition134
X-Linked Conditions
Coffin-Lowry135–139
Ectodermal dysplasia 1140–142
Ectodermal dysplasia, hypohidrotic, with
hypothyroidism and agenesis
of the corpus callosum143
Causation
Prominent Features Locus/Gene
Anomalies of MUscle, LIver, (253250)
BRain, and EYe TRIM37, 17q32–q23
Tetramelic deficiency, ectodermal (273400)
dysplasia, deformed pinnae
Postaxial polydactyly and other (263540)
abnormalities of the hands
and feet, hypoplasia and fusion
of vertebral bodies, dental anomalies
Precocious senility of a striking (176670)
degree; death from coronary LMNA, 1q21.2
artery disease is frequent and
may occur before 10 years of age
Deformity of the skull, maxilla, (265800)
and phalanges; osteosclerosis; CTSK, 1q21
fragility of bone; dental anomalies
Robin sequence, cleft mandible, (268305)
limb anomalies
Atrophy, pigmentation, (268400)
telangiectasia, juvenile cataract, RECQL4, 8q24.3
saddle nose, congenital bone
defects, disturbances of hair
growth, hypogonadism, dental
anomalies, soft tissue contractures,
proportionate short stature,
anemia, osteogenic sarcoma
Generalized platyspondyly with (601668)
epiphyseal and metaphyseal
involvement, thin tapering
fingers with accentuated palmar
creases, abnormal dentition
(oligodontia and pointed incisors)
Mental retardation with peculiar (303600)
pugilistic nose, large ears, tapered RSK2, Xp22.2-p22.1
fingers, drumstick terminal
phalanges by radiograph, and
pectus carinatum. Other
complications: premature death,
progressive kyphoscoliosis,
spinal stenosis, drop attacks,
abnormalities in dentition,
hearing loss, ocular abnormalities,
excess of psychiatric
illness in carrier females
Males: characteristic facies; teeth (305100)
often missing or misshapen; fine, ED1, Xq12-q13.1
sparse hair; and skin is thin, glossy,
smooth, and dry with hypohidrosis.
Females: sparse, thin scalp hair and
mosaic patchy distribution of body
hair; abnormal teeth;
mild hypohidrosis
(225040)
(continued)
437
 Table 14-4. Syndromes with tooth agenesis as a component (continued)
Syndrome
Faciogenital dysplasia144–148
Focal dermal hypoplasia149
Frontometaphyseal dysplasia150
Incontinentia pigmenti151
Mulvihill-Smith152
Oculofaciocardio-dental153–155
Orofaciodigital, type I156,157
Otopalatodigital types I and II150,158
W159
Chromosomal and Other Conditions
Anauxetic dysplasia160
Down161–165
Glossopalatine ankylosis166
Hemimaxillofacial dysplasia167
438
Causation
Prominent Features Locus/Gene
Ocular hypertelorism, anteverted nostrils, (305400)
broad upper lip, escrotum anomalies, FGD1, Xp11.21
occasional dental anomalies
Atrophy and linear pigmentation of the (305600)
skin, herniation of fat through
the dermal defects, multiple
papillomas of the mucous
membranes or skin, digital
anomalies, oral anomalies, ocular
anomalies, mental retardation
Marked frontal hyperostosis, (305620)
underdeveloped mandible, FLNA, Xq28
cryptorchidism, subluxated
radial heads, metaphyseal dysplasia
Disturbance of skin pigmentation (308300)
sometimes associated with a NEMO, Xq28
variety of malformations of the eye,
teeth, skeleton, and heart
Low-birth-weight dwarfism with (176690)
mild to moderate mental
retardation, striking multiple
pigmented nevi, lack of facial
subcutaneous fat
Cataracts, micro-phthalmia, (300166)
oligodontia, radiculomegaly, BCL6 corepressor (BCOR)
septal heart defects
Clefts of the jaw and tongue, (311200)
other malformations of the CXORF5, Xp22.3-p22.2
face and skull, malformations
of the hands and teeth,
mental retardation
Conduction deafness, cleft palate, (311300, 304120)
characteristic facies, generalized bone FLNA, Xq28
dysplasia; type II is more severe
Mental retardation with frontal (311450)
prominence; anterior cowlick;
hypertelorism; antimongoloid
orbital slant; broad, flat nasal bridge;
midline notch of upper lip and
submucous cleft of the hard palate;
absent upper central incisors;
limited motion at the elbow;
pes cavus
Short stature, hypotelorism, prognathism, (607095)
hypodontia
Mental retardation, typical facies, (190685)
heart defects, short stature, Trisomy 21
dental anomalies
Glossopalatine ankylosis, cleft palate,
limb anomalies, hypoplastic
mandible, incisor hypodontia
Unilateral enlargement of maxillary
alveolar bone and gingival associated
with tooth agenesis, facial asymmetry
(continued)
 Teeth 439

Table 14-4. Syndromes with tooth agenesis as a component (continued)

Causation
Syndrome Prominent Features Locus/Gene

Oroacral, Verloes-Koulischer type168 Absence of the medial part of the (603446)

upper alveolar ridge, including
the gingiva, frenulum, and tooth
buds for the maxillary incisors and
canines
Sener169 Frontonasal dysplasia, dilated (606156)
Virchow-Robin spaces,
hypodontia, buccal frenula
Unusual facies, oligodontia, Minor digital anomalies, telecanthus, (603589)
and precocious choroid calcifications170 broad and flattened nasal bridge,
mild ocular proptosis, small nose with
anteverted nostrils, microretrognathia
Williams-Beuren171 Typical facies, mental retardation, (194050)
growth deficiency, cardio-vascular 7q11.23
anomalies, infantile hypercalcemia
Wolf-Hirschhorn172 Severe growth retardation and mental (194190)
defect, microcephaly, typical facies, Chromosomal Del 4p16.3
closure defects (cleft lip or palate,
coloboma of the eye, cardiac septal defects)

Table 14-5. Solitary maxillary central incisor defects Table 14-6. Epidemiologic Characteristics of Tooth Agenesis
Causation Characteristic Summary Information
Type of Defect Associated Gene/Locus 207
Frequency (primary dentition) 1.4%
Isolated defect173 AD (147250) Frequency (permanent 1.6–10%
SHH, 7q36 dentition, excluding
7q36.1 deletion174 Chromosomal third molars)208,209
Del 7q36.1 Ethnic differences210 Frequencies are
18p deletion or r(18)175–178 Chromosomal higher in Asians and lower
Del 18p or ring 18 in African-descent populations
CHARGE179,180 Multifactorial compared to Europeans
(214800) Gender differences211,212 M/F 2:3
Hypophyseal Unknown Familial patterns1,213,214 Approximately 35% are familial cases
short stature and cleft lip181 Sibling recurrence 1–9%
Holoprosencephaly182–194 Heterogeneous Monozygotic twin concordance 89%
(236100)
SHH, 7q36
SIX3, 2p21
TGIF, 18p13
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14.2
Supernumerary Teeth
Definition
Supernumerary teeth is the presence of more than the normal
complement of deciduous (20) and permanent teeth (32).
Diagnosis
Supernumerary teeth can be diagnosed by the actual count, clini-
cally or radiographically. Teeth in excess of the normal comple-
ment are named according to their location: mesiodens are located
on the palatal side of the maxillary central incisors; supernumerary
canines and premolars are located at the normal sites for such teeth;
paramolars are located buccal to the first, second, and third molars;
and distomolars (fourth molars) are located distal to the third
molar in line with the dental arch. There may also be lingual, intra-
dental, and interradicular supernumerary teeth. Supernumerary
teeth may be fused with teeth in the normal complement. Super-
numerary teeth can present as the only phenotypic feature (iso-
lated), in association with other anomalies (such as tooth agenesis
or orofacial clefts), or as part of a syndrome.1–3
Etiology and Distribution
Syndromes with supernumerary teeth as a component are listed
in Table 14-7. There is evidence that related etiologic factors
contribute to supernumerary teeth, tooth agenesis, and orofacial
clefts.3,33,34 Differences in the mesiodistal width of central incisors
depending on unilateral or bilateral occurrence of mesiodens and
the report of gemination of a deciduous incisor on the same side
of a mesiodens support the theory of the split in the tooth bud
inducing the development of supernumerary teeth over that of
a local hyperactivity of the dental lamina.33 Single and double
supernumeraries occur in 90% of cases, and multiple supernu-
meraries in 10% of cases.35 Epidemiologic characteristics of su-
pernumerary teeth are listed in Table 14-8.
Prognosis, Treatment, and Prevention
Supernumerary teeth may interfere with the eruption of teeth in
the normal complement or may cause their malalignment. Unless
they are features of a syndrome, prognosis is good. They are easily
extracted, even if they are impacted. There are no preventive
measures.
References (Supernumerary Teeth)
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1999.
 Teeth 445

Table 14-7. Syndromes with supernumerary teeth as a component

Syndrome Prominent Features Causation Gene/Locus

Autosomal Dominant Conditions

Adenomatous polyposis of the colon4,5
Cleidocranial dysplasia6,7
Gingival fibromatosis, hearing
loss, and supernumerary teeth8
Hallermann-Streiff9
LEOPARD10–12
Trichorhino-phalangeal types
I and III13,14
Uncombable hair, retinal pigmentary
dystrophy, dental anomalies,
brachydactyly15,16
Unusual facies, digital anomalies,
supernumerary teeth17
Adenomatous polyps of the colon and rectum, (175100)
congenital hypertrophy of the retinal pigment APC, 5q21–q22
epithelium, dental anomalies
Persistently open skull sutures with bulging calvaria, (119600)
hypoplasia or aplasia of the clavicles permitting abnormal CBFA1 (RUNX2), 6p21
facility in apposing the shoulders, wide pubic symphysis,
short middle phalanx of the fifth fingers, supernumerary
teeth, vertebral malformations
Gingival overgrowth at the time of deciduous tooth eruption, Unknown
hearing loss, supernumerary teeth, hypertelorism
Birdlike facies with hypoplastic mandible and beaked nose, (234100)
proportionate dwarfism, hypotrichosis, microphthalmia,
dental anomalies, congenital cataract
Multiple lentigines, electrocardiographic conduction (151100)
abnormalities, ocular hypertelorism, pulmonic stenosis, PTPN11, 12q24.1
abnormal genitalia, retardation of growth, sensorineural
deafness, delayed secondary sexual characteristics,
supernumerary teeth
Sparse hair, beaked nose, long upper lip, super-numerary teeth, (190350, 190351)
severe metacarpophalangeal shortening TRPS1 18q24.12
Congenital hypotrichosis and uncombable hair, associated with (191482)
juvenile cataracts, retinal pigmentary dystrophy, oligodontia,
brachymetacarpy
Prominent forehead with widow’s peak, supernumerary teeth, AD
subglottic tracheal hypoplasia, brachydactyly, club foot, clinodactyly

Autosomal Recessive Conditions

Oral-facial-digital with retinal
anomalies18
Rothmund-Thomson19,20
Steroid dehydrogenase deficiency21
Mild mental retardation; small notch in the upper lip; highly (258865)
arched palate with bifid tongue; supernumerary lower canine
bilaterally; lobulated, hamartomatous tongue; multiple frenula
(could also be X-linked)
Atrophy, pigmentation, telangiectasia, juvenile cataract, saddle (268400)
nose, congenital bone defects, disturbances of hair growth, RECQL4, 8q24.3
hypogonadism, dental anomalies, soft tissue contractures,
proportionate short stature, anemia, osteogenic sarcoma
Supernumerary teeth, steroid dehydrogenase deficiency Unknown

X-Linked Conditions

Cataract-dental22–28 Dense nuclear cataracts and frequently microcornea with (302350)

Focal dermal hypoplasia29
Orofaciodigital, types I, III30–32
mesiodens and incisor anomalies Xp22.13
Atrophy and linear pigmentation of the skin, herniation of fat (305600)
through the dermal defects, and multiple papillomas of the
mucous membranes or skin, digital anomalies, oral anomalies,
ocular anomalies, mental retardation
Clefts of the jaw and tongue, other malformations of the face and (311200, 258850)
skull, malformation of the hands and teeth, mental retardation CXORF5, Xp22.3–p22.2

21. Lyngstadaas SP, Crossner CJ, Nazer H, et al.: Severe dental aberrations
in familial steroid dehydrogenase deficiency: a new association. Clin
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22. Bixler D, Higgins M, Hartsfield J Jr: The Nance-Horan syndrome: a rare
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Clin Genet 26:30, 1984.
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cause the pleiotropic effects of Nance-Horan syndrome, including severe
446 Craniofacial Structures

Table 14-8. Epidemiologic characteristics of supernumerary crodontia is usually determined subjectively. Microdontia may affect
teeth only a few teeth, usually homologous teeth such as the maxillary
Characteristic Summary Information lateral incisors, or may be generalized. It may be an isolated trait,
may be associated with tooth agenesis or orofacial clefts, or may be
Frequency <0.1%
one feature in syndromes.1–6
(primary dentition)36
Frequency (permanent 1–5% Etiology and Distribution
dentition)37–39
Syndromes with microdontia as a component are listed in Table 14-
Ethnic differences37–39 No remarkable differences 10. It is likely that microdontia is a variable expression of tooth
in frequency among populations
agenesis and therefore is probably multifactorial in etiology. The
Gender differences39–42 M/F 2:1 in Europeans; 4:1 in more severe the tooth agenesis, the smaller the size of the tooth
Africans; 5.5:1 in Japanese; formed.3 Individuals with agenesis of one upper lateral incisor
and 6.5:1 in Chinese
present with a 13-fold increased risk of having microdontia involving
Familial patterns33 Approximately 30% are familial cases the contralateral upper lateral incisor. Also, cases with molar agenesis
have a fourfold increased risk of having microdontia involving an
upper lateral incisor. The suggestive association between molar
congenital cataract, dental anomalies, and mental retardation. Am J Hum agenesis and microdontia of the upper lateral incisor provides evi-
Genet 73:1120, 2003. dence that incisors and molars share some developmental genetic
29. Hall EH, Terezhalmy GT: Focal dermal hypoplasia syndrome. J Am mechanisms, which appear to be independent from those that reg-
Acad Dermatol 9:443, 1983. ulate premolar development.85 This is in agreement with the pattern
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 Teeth 447

Table 14-9. Average sizes of permanent and deciduous teeth

Permanent Deciduous
Heighta Widthb Heighta Widthb

Maxillary

Central incisors 10.5 8.5  7.0 6.0 6.5  5.0

Lateral incisors 9.0 6.5  6.0 5.6 5.0  4.0
Canines 10.0 7.5  8.0 6.5 7.0  7.0
First premolars 8.5 7.0  9.0 — —
Second premolars 8.5 7.0  9.0 — —
First molars 7.5 10.0  11.0 5.1 7.3  8.5
Second molars 7.0 9.0  11.0 5.7 8.2  10.0
Third molars 6.5 8.5  10.0 — —

Mandibular

Central incisors 9.0 5.0  6.0 5.0 4.2  4.0

Lateral incisors 9.5 5.5  6.5 5.2 4.1  4.0
Canines 11.0 7.0  7.5 6.0 5.0  4.8
First premolars 8.5 7.0  8.0 — —
Second premolars 8.0 7.0  8.0 — —
First molars 7.5 11.0  10.5 6.0 7.7  7.0
Second molars 7.0 10.5  10.5 5.5 9.9  8.7
Third molars 7.0 10.0  9.5 — —
a
Height of crown in cm.
Mesiodistal width  buccolingual (buccopalatal) width in cm.
b

Modified from Renner.7

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Table 14-10. Syndromes with microdontia as a component
Syndrome
Autosomal Dominant Conditions
Ankyloblepharon-ectodermal defects-cleft
lip/palate8,9
Axenfeld-Rieger10–15
Ectodermal dysplasia 316,17
Ehlers-Danlos type VI18–20
Hair-nail-skin-teeth dysplasias21
Niikawa-Kuroki (Kabuki)22–24
Oculodento-digital dysplasia25,26
Otodental dysplasia27
Symphalangism, Kantaputra type28
Uncombable hair, retinal pigmentary
dystrophy, dental anomalies, brachydactyly29,30
Witkop (tooth-and-nail)31
Autosomal Recessive Conditions
Cartilage-hair hypoplasia32–35
Cleft lip/palate, congenital contractures,
ectodermal dysplasia, and
psychomotor and growth retardation36
Cleft lip/palate-ectodermal dysplasia37,38
448
Causation
Prominent Features Gene/Locus
Coarse, wiry, sparse hair; dystrophic (106260)
nails; slight hypohidrosis; scalp p63, 3q27
infections; ankyloblepharon
filiforme adnatum; hypodontia;
maxillary hypoplasia; cleft lip/palate
Eye, dental, and umbilical anomalies (180500)
PITX2, 4q25-q26
FOXC1, 6p25
13q14
Mild hypotrichosis, mild hypodontia, (129490)
variable degrees of hypohidrosis EDAR, 2q11-q13
(can also be autosomal recessive)
Ocular, muscular, and skin defects; (225400)
abnormal maxilla; occasional PLOD1, 1p36.3–p36.2
hypodontia and/or smaller teeth sizes
Large number of rare disorders (125640, 257980, 262020,
involving binary, ternary, or quaternary 272980, 275450)
combination of hair, nails, skin appendages,
and teeth anomalies (can also be
autosomal recessive or X-linked)
A peculiar face, characterized by eversion (147920)
of the lower lateral eyelid, arched eyebrows
with sparse or dispersed lateral one-third,
depressed nasal tip, prominent ears, skeletal
anomalies, dermatoglyphic abnormalities,
mild to moderate mental retardation,
postnatal growth deficiency, heart defects,
dental anomalies
Bilateral microphthalmos, abnormally (164200)
small nose, hypotrichosis, dental anomalies, GJA1, 6q21–q23.2
fifth finger camptodactyly, syndactyly of the
fourth and fifth fingers, missing toe phalanges
Sensorineural hearing loss, dental anomalies, (166750)
missing premolars
Distal symphalangism, microdontia, dental (606895)
pulp stones, narrowed zygomatic arch
Congenital hypotrichosis and uncombable hair, (191482)
associated with juvenile cataracts, retinal
pigmentary dystrophy, oligodontia, and
brachymetacarpy
Missing teeth and poorly formed nails (189500)
MSX1, 4p16.1
Short-limbed dwarfism due to skeletal dysplasia, (250250)
sparse hair, dental anomalies, lymphopenia, RMRP, 9p21–p12
anemia, neutropenia
Typical facies, congenital contractures, (301815)
orofacial clefts, oligodontia and other
teeth anomalies (may be X-linked)
Anhidrosis, hypotrichosis, dental anomalies, (225000)
dysplasia of nails, cleft lip and palate, PVRL1, 11q23–q24
deformity of the fingers and toes,
malformation in the genitourinary system,
popliteal perineal pterygium, syndactyly
(continued)
Table 14-10. Syndromes with microdontia as a component (continued)
Causation
Syndrome Prominent Features Locus/Gene

Cranioectodermal dysplasia39 Dolichocephaly; sparse, slow-growing, fine hair; (218330)

epicanthal folds; hypodontia and/or microdontia;
brachydactyly; narrow thorax
Ectodermal dysplasia, Margarita Scanty eyebrows and eyelashes; sparse, short, and (225060)
Island type38,40 dry scalp hair; dental anomalies; cleft lip/palate; PVRL1, 11q23–q24
syndactyly of fingers and toes; onychodysplasia
Ellis-van Creveld41–43 Skeletal dysplasia characterized by short limbs, (225500)
short ribs, postaxial polydactyly, dysplastic EVC, EVC2
nails and teeth
Gorlin-Chaudhry-Moss44 Craniofacial dysostosis, hypertrichosis, hypoplasia (233500)
of labia majora, dental and eye anomalies, patent
ductus arteriosus, normal intelligence
Immunoosseous dysplasia, Combination of spondyloepiphyseal dysplasia and (242900)
Schimke type45–47 numerous lentigines; microdontia and other SMARCAL1
dental abnormalities; slowly progressive immune
defect; immune-complex nephritis, which leads to
death at about age 8 years
Larsen48,49 Bilateral dislocation of the knees, pes cavus, (150250)
cylindrically shaped fingers, characteristic facies FLNB
(can also be autosomal dominant)
Microcephalic osteodysplastic Dwarfism, microcephaly, characteristic facies, bone (210720)
dwarfism, type II50,51 anomalies, microdontia
Odontotrichomelic52 Tetramelic deficiency, ectodermal dysplasia, (273400)
deformed pinnae
Polydactyly, postaxial, with Postaxial polydactyly and other abnormalities of the (263540)
dental and vertebral anomalies53 hands and feet, hypoplasia and fusion of vertebral
bodies, dental anomalies
Rothmund-Thomson54,55 Atrophy, pigmentation, telangiectasia, juvenile (268400)
cataract, saddle nose, congenital bone defects, RECQL4, 8q24.3
disturbances of hair growth, hypogonadism,
dental anomalies, soft tissue contractures,
proportionate short stature, anemia,
osteogenic sarcoma
Spondyloepimetaphyseal Generalized platyspondyly with epiphyseal and (601668)
dysplasia with abnormal dentition56 metaphyseal involvement, thin tapering fingers
with accentuated palmar creases, abnormal
dentition (oligodontia and pointed incisors)

X-Linked Conditions

Coffin-Lowry57–61 Mental retardation with peculiar pugilistic nose, (303600)

Ectodermal dysplasia 162–64
Ectodermal dysplasia, hypohidrotic,
with hypothyroidism and agenesis
of the corpus callosum65
large ears, tapered fingers, drumstick terminal RSK2, Xp22.2–p22.1
phalanges by radiograph, and pectus carinatum
Other complications: premature death, progressive
kyphoscoliosis, spinal stenosis, drop attacks,
abnormalities in dentition, hearing loss, ocular
abnormalities, excess of psychiatric illness in
carrier females
Males: characteristic facies; teeth often missing or (305100)
misshapen; fine, sparse hair; skin is thin, glossy, ED1, Xq12–q13.1
smooth, and dry with hypohidrosis
Females: sparse, thin scalp hair and mosaic patchy
distribution of body hair; abnormal teeth
and mild hypohidrosis
Severe mental retardation, macrocephaly, (225040)
hypertelorism, short and downward slanting eyelids,
small nose and mouth, dysplastic and low-set ears,
swallowing difficulties, reduced sweating, sparse scalp
hair, delayed dentition, small teeth with defective enamel
(continued)

449
450 Craniofacial Structures

Table 14-10. Syndromes with microdontia as a component (continued)

Causation
Syndrome Prominent Features Locus/Gene

Faciogenital dysplasia66–70 Ocular hypertelorism, anteverted (305400)

nostrils, broad upper lip, escrotum anomalies, FGD1, Xp11.21
occasional dental anomalies
Focal dermal hypoplasia71 Atrophy and linear pigmentation of the skin, (305600)
herniation of fat through the dermal defects,
multiple papillomas of the mucous membranes
or skin, digital anomalies, oral anomalies, ocular
anomalies, mental retardation
Incontinentia pigmenti72 Disturbance of skin pigmentation sometimes (308300)
associated with a variety of malformations of the NEMO, Xq28
eye, teeth, skeleton, and heart
Johanson-Blizzard73 Aplasia or hypoplasia of the nasal alae, congenital (243800)
deafness, hypothyroidism, postnatal growth
retardation, mental retardation, midline ectodermal
scalp defects, and microdontia or absent permanent teeth
Orofaciodigital, type I74,75 Clefts of the jaw and tongue, other malformations (311200)
of the face and skull, malformation of the hands CXORF5, Xp22.3–p22.2
and teeth, and mental retardation

Chromosomal and Other Conditions

Down76–81 Mental retardation, typical facies, heart defects, (190685)

short stature, dental anomalies Trisomy
Microcephaly, macrotia, and Microcephaly, mental retardation, huge ears with very (602555)
mental retardation82 large lobules, median frenulum of the upper lip,
ptosis, microdontia, bilateral ureterohydronephrosis
secondary to vesicoureteral reflux (can be autosomal
dominant or X-linked)
Microcephalic osteodysplastic primordial Growth retardation, opalescent and rootless teeth, severe microdontia, (607561)
dwarfism with tooth abnormalities83 hypoplastic alveolar process, unerupted teeth, long second toes
Williams-Beuren84 Typical facies, mental retardation, growth deficiency, (194050)
cardiovascular anomalies, infantile hypercalcemia 7q11.23

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76. Down JL: Observations on an ethnic classification of idiots. Clin Lect
Rep London Hospital 3:249, 1866.
451
77. Lejeune J, Gautier M, Turpin R: Etude des chromosomes somatiques
de neuf enfants mongoliens. C R Hebd Seances Acad Sci 248:1721,
1959.
78. Mikkelsen M: Down’s syndrome cytogenetic epidemiology. Hereditas
86:45, 1977.
79. Hook EG: Epidemiology of Down syndrome. In: Down Syndrome.
Advances in Biomedicine and the Behavioral Sciences. Pueschel SM,
Rynders JE, eds. Ware Press, Cambridge, 1982, p 11.
80. Thuline HC, Pueschel SM: Cytogenetics in Down syndrome. In: Down
Syndrome. Advances in Biomedicine and the Behavioral Sciences.
Pueschel SM, Rynders JE, eds. Ware Press, Cambridge, 1982, p 133.
81. Shapira J, Chaushu S, Becker A: Prevalence of tooth transposition,
third molar agenesis, and maxillary canine impactation in individuals
with Down syndrome. Angle Orthod 70:290, 2000.
82. Verloes A, Lesenfants S, Philippet B, et al.: Microcephaly, macrotia,
unusual mimics and mental retardation syndrome: new syndrome or
variant of de Lange type 2 syndrome. Genet Couns 7:277, 1996.
83. Kantaputra PN: Apparently new osteodysplastic and primordial short
stature with severe microdontia, opalescent teeth, and rootless molars
in two siblings. Am J Med Genet 111:420, 2002.
84. Ewart AK, Morris CA, Atkinson D, et al.: Hemizygosity at the elastin
locus in a developmental disorder, Williams syndrome. Nat Genet
5:11, 1993.
85. Barbosa ARS, Modesto A, Meira R, et al.: Molar agenesis is associated with
abnormalities of superior lateral incisors. In: International Association for
Dental Research 82nd General Session Program Book, 2004, p 194.
86. Vieira AR: Oral clefts and syndromic forms of tooth agenesis as models
for genetics of isolated tooth agenesis. J Dent Res 82:162, 2003.
87. Saito T: A genetic study on the degenerative anomalies of deciduous
teeth. Jpn J Hum Genet 4:27, 1959.
88. Schulze C: Developmental abnormalities of the teeth and jaws. In:
Thoma’s Oral Pathology. Gorlin RJ, Goldman HM, eds. Mosby, St.
Louis, 1970.
89. Sumiya Y: Statistical study on dental anomalies in the Japanense.
J Anthropol Soc Nippon 67:171, 1959.
14.4
Macrodontia
Definition
Macrodontia is a tooth that is much larger than its contralateral
homolog or teeth from the same group from an opposing arch (the
maxillary central incisors are exceptions); a tooth that ‘‘overfills’’
its space in the dental arch, crowds out adjacent teeth, or is rotated
to accommodate its size; or a tooth that appears large because of
exaggerated dimension. Fused teeth (joining of two teeth by the
pulp tissue and dentin) and germination (budding of a second
tooth from one tooth germ) might fit well into the later category.
Diagnosis
Macrodontia is diagnosed by simple observation or measurement
and comparison with standards for tooth size (Table 14-9). Even
though there are anatomic standards, the criteria stated above are the
most useful to the clinician. Macrodontia is usually an isolated trait
but can be accompanied by other dental anomalies or occur as part
of a syndrome.1–3 Also, patients with supernumerary teeth present
significantly larger teeth compared to the general population.4
Etiology and Distribution
Syndromes with macrodontia as a component are listed in Table
14-11. Because of the association with sexual chromosome anoma-
lies, it appears that there are dental growth-promoting factors on
both the X and the Y chromosomes. The promoting effect of the Y
chromosome on tooth growth seems to be stronger than that of the
452 Craniofacial Structures

Table 14-11. Syndromes with macrodontia as a component

Causation
Syndrome Prominent features Gene/Locus

KBG5 Short stature, characteristic facies, mental retardation, skeletal AD (148050)

Polydactyly, postaxial, with dental
and vertebral anomalies6
Oculofaciocardio-dental7–9
47, XXY (Klinefelter)10
47, XYY11,12
Hemihyperplasia13,14
anomalies, oligodontia, macrodontia
Postaxial polydactyly and other abnormalities of the hands and feet, AR (263540)
hypoplasia and fusion of vertebral bodies, dental anomalies
Cataracts, microphthalmia, oligodontia, radiculomegaly, septal heart defects XL (300166)
BCL6 corepressor (BCOR)
Tall stature, delayed speech in 50% of the cases, behavior disorders (314240)
Chromosomal
Tall stature, 1/3 of the cases will present with delayed speech (314240)
or language development, higher risk for criminal behavior Chromosomal
The enlarged area may vary from a single digit, a single limb, or Sporadic (235000)
unilateral facial enlargement to involvement of half the body 11p15

X chromosome.10 Occasionally, exaggerated tooth size is seen in
conjunction with absence of an adjacent tooth, suggesting that the
large tooth may be fusion of two adjacent teeth. The frequency of
macrodontia is unknown; it is certainly rare.
13. Gorlin RJ, Meskin LH: Congenital hemihypertrophy. J Pediatr 61:870,
1962.
14. West PMH, Love DR, Stapleton PM, et al.: Paternal uniparental
disomy in monozygotic twins discordant for hemihypertrophy. J Med
Genet 40:223, 2003.

Prognosis, Treatment, and Prevention

There are no morbid features associated with isolated macro-
dontia. Malalignment of adjacent tooth and malocclusion can
occur, depending on the site and extent of macrodontia. Treat-
ment may be indicated for aesthetic reasons. There are no useful
preventive measures for macrodontia.
References (Macrodontia)
1. Ekman-Westborg B, Julin P: Multiple anomalies in dental morphol-
ogy: macrodontia, multituberculism, central cusps, and pulp invagi-
nations. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 38:217,
1974.
2. Ritzau M, Carlsen O, Kreiborg S, et al.: The Ekman-Westborg-Julin
syndrome: report of a case. Oral Surg Oral Med Oral Pathol Oral
Radiol Endod 84:293, 1997.
3. Yoda T, Ishii Y, Honma Y, et al.: Multiple macrodonts with odontoma
in a mother and son—a variant of Ekman-Westborg-Julin syndrome.
Report of a case. Oral Surg Oral Med Oral Pathol Oral Radiol Endod
85:301, 1998.
4. Brook AH, Elcock C, al-Sharood MH, et al.: Further studies of a model
for the etiology of anomalies of tooth number and size in humans.
Connect Tissue Res 43:289, 2002.
5. Herrmann J, Pallister PD, Tiddy W, et al.: The KBG syndrome—a
syndrome of short stature, characteristic facies, mental retardation,
macrodontia amd skeletal anomalies. Birth Defects Orig Artic Ser XI(5),
1975.
6. Rogers JG, Levin LS, Dorst JP, et al.: A postaxial polydactyly-dental-
vertebral syndrome. J Pediatr 90:230–235, 1977.
7. Shepard MK: An unidentified syndrome with abnormality of skin and
hair. Birth Defects Orig Artic Ser VII(8):353, 1971.
8. Hayward JR: Cuspid gigantism. Oral Surg Oral Med Oral Path Oral
Radiol Endod 49:500, 1980.
9. Gorlin RJ, Marashi AH, Obwegeser HL: Oculo-facio-cardio-dental
(OFCD) syndrome. Am J Med Genet 63:290, 1996.
10. Alvesalo L, Portin P: 47,XXY males: sex chromosomes and tooth size.
Am J Hum Genet 32:955, 1980.
11. Alvesalo L, Osborne RH, Kari M: The 47,XYY male, Y chromosome,
and tooth size. Am J Hum Genet 27:53, 1975.
12. Alvesalo L, Kari M: Size and deciduous teeth in 47, XYY males. Am J
Hum Genet 29:486, 1977.
14.5
Abnormalities of Tooth Shape
Definition
Abnormalities of tooth shape occur in the crowns or roots of teeth.
Crown form may be entirely distorted with the loss of the usual
cusp and groove relationships (globodontia), or the crowns may
have abnormal or supernumerary cusps (referred as talon cusps for
incisors and canines and supernumerary cusps for premolars and
molars) or invaginations (dens invaginatus). Shovel-shaped inci-
sors are yet another variation of crown shape. Roots may be fore-
shortened or bent (dilacerated), or there may be supernumerary
roots. The pulp chambers can be vertically enlarged (taurodontia).
Diagnosis
Globodontia, talon cusps, supernumerary cusps, dens invaginatus,
shovel-shaped incisors, dilacerations, supernumerary roots, and
taurodontia may occur as isolated traits or be associated with tooth
agenesis, supernumerary teeth, microdontia, or macrodontia. More
than one abnormality of tooth shape can be present in the same case.
Abnormalities of tooth shape can be part of various syndromes.
Short stature is often described as accompanying abnormalities of
tooth shape.1–15 Globodontia can be the only obvious feature in
someone with otodental dysplasia, an autosomal dominant trait that
presents with sensorineural hearing loss and dental anomalies.16
Abnormalities of crown shape are determined clinically. Di-
lacerated and supernumerary roots and taurodontia can be de-
termined by radiographs.
Etiology and distribution
Syndromes with shovel-shaped and other incisor abnormalities as
a component are listed in Table 14-12, and those with globo-
dontia or supernumerary cusps as a component are listed in Table
14-13, and those with taurodontia as a component are listed in
Table 14-14. Globodontia is probably not seen as an isolated trait.
It is found in otodental dysplasia, an autosomal dominant syn-
 Teeth 453

Table 14-12. Syndromes with shovel-shaped and other incisor abnormalities as a component
Causation
Syndrome Prominent Features Gene/Locus

Rubinstein-Taybi17–22 Mental retardation, broad thumbs, and facial abnormalities; AD (180849)

Orofaciodigital type II23,24
Cataract-dental25–31
Incontinentia pigmenti32,33
47, XXY (Klinefelter)34,35
47, XYY36,37
Down38–42 (190685)
Congenital syphilis43
Sturge-Weber19,44,45
90% of the cases present with talon cusps CREBBP, 16p13.3
Poly-, syn-, and brachydactyly, lobate tongue with papilliform AR (252100)
protuberances, angular form of the alveolar process of the
mandible, supernumerary sutures in the skull, neuromuscular
disturbances, cleft palate, and talon cusps
Dense nuclear cataracts and frequently microcornea with XL (302350)
mesiodens and incisors of Hutchinson Xp22.13
Disturbance of skin pigmentation sometimes associated XL (308300)
with a variety of malformations of the eye, teeth, skeleton, and heart NEMO, Xq28
Tall stature, delayed speech in 50% of the cases, behavior (314240)
disorders, occasional shovel-shaped incisors Chromosomal
Tall stature, 1/3 of the cases will present with (314240)
delayed speech or language development, higher risk for criminal Chromosomal
behavior, occasional shoved-shaped incisors
Mental retardation, typical facies, heart defects, short Trisomy 21
stature, dental anomalies
Skin ulcers, rashes, fever, weakened or hoarse crying sounds, swollen Prenatal infection
liver and spleen, yellowish skin, anemia, bone deformities,
incisors of Hutchinson
Nevus flammeus of the face, angioma of the meninges, Sporadic (185300)
glaucoma, occasional talon cusps 4q, chromosome 10

Table 14-13. Syndromes with globodontia or supernumerary cusps as a component

Causation
Syndrome Prominent Features Gene/Locus

Otodental dysplasia16 Sensorineural hearing loss, dental AD (166750)

Cartilage-hair hypoplasia46–49
Rothmund-Thomson50,51
anomalies, missing premolars
Short-limbed dwarfism due to skeletal AR (250250)
dysplasia, sparse hair, dental anomalies RMRP, 9p21–p12
(supernumerary cusps), lymphopenia,
anemia, neutropenia
Atrophy, pigmentation, telangiectasia, AR (268400)
juvenile cataract, saddle nose, congenital RECQL4, 8q24.3
bone defects, disturbances of hair growth,
hypogonadism, dental anomalies, soft tissue
contractures, proportionate short stature,
anemia, osteogenic sarcoma

drome, and in Rothmund-Thomson syndrome, an autosomal
recessive condition.16,50,51 The etiology of supernumerary cusps is
unknown, although the differences in the prevalences of such
abnormality among males and females suggest a multifactorial
trait (male to female ratio is 1:2). Supernumerary cusps have a
prevalence in the population as high as 47.6%.15
Dens invaginatus is probably a multifactorial trait with higher
frequencies in those of Chinese, Japanese, Native Americans, and
Eskimos, compared to European and African descents.15,90–93
Shovel-shaped incisors are more common among Native Ameri-
cans, Inuit, and Asian populations (60–75%) compared to other
ethnic groups, and it is probably a multifactorial trait.94
The cause for dilacerated and supernumerary roots is unknown;
however, roots can be dilacerated as a consequence of trauma to
erupting teeth. The supernumerary roots may be due to the dis-
turbances of the Hertwig’s epithelial root sheath forming the
root.95,96 Taurodontia can be caused by a delay in the formation of
horizontal extensions of Hertwig epithelial root sheath, whose in-
vagination determines the position of the pulpal floor. Taurodontia
has been reported in 0.5% of those of Japanese descent, 0.57–3.2% of
those of European descent, and 4.37% of those of African descent. It
is probably a multifactorial trait, although there have been a few
reported families in which it appears to be transmitted in an auto-
somal dominant fashion.97
Prognosis, Treatment, and Prevention
None of the abnormalities discussed above is morbid or progres-
sive. At most, they complicate certain types of dental treatment:
endodontics (root canal therapy) and extractions. Prevention is not
possible or necessary.
454 Craniofacial Structures

Table 14-14. Syndromes with taurodontia as a component

Causation
Syndrome Prominent Features Gene/Locus

Autosomal Dominant Conditions

Apert52–58 Skull malformation (acrocephaly of brachysphenocephalic type) and syndactyly (101200)

Axenfeld-Rieger52,59–64
Basal-cell nevus52,65,66
Ectodermal dysplasias52
Otodental dysplasia52
Trichodentoosseous52,67,68
of the hands and feet of a special type (complete distal fusion with a FGFR2, 10q26
tendency to fusion also of the bony structures)
Eye, dental, and umbilical anomalies (180500)
PITX2, 4q25–26
FOXC1, 6p25 13q14
Basal cell nevi; medulloblastoma; congenital thoracic scoliosis; astrocytoma (109400)
with severe hydrocephalus; the palms and soles may show pits; bridging PTCH2, 9q22.3
of the sella turcica; mild mandibular prognathism; lateral displacement of
the inner canthi; frontal and biparietal bossing; odontogenic keratocysts
of the jaws; kyphoscoliosis; bifid, missing, fused, and/or splayed ribs;
imperfect segmentation of cervical vertebrae; characteristic lamellar
calcification of the falx cerebri; ovarian fibromata and lymphomesenteric
cysts, which tend to calcify; short fourth metacarpal
Large number of disorders characterized by hair, skin, dental, and nail Genes for the most
anomalies (can also be autosomal recessive or X-linked) common forms
have been identified
Sensorineural hearing loss, dental anomalies, including missing premolars (166750)
Enamel hypoplasia and hypocalcification with associated strikingly curly hair (190320)
DLX3

Autosomal Recessive Conditions

Ackerman69 Pyramidal molar roots, taurodontia, fused molar roots, juvenile (200970)
glaucoma, unusual upper lip

X-Linked Conditions

Dyskeratosis congenita52,70–74
Fragile X52,75–78
Orofaciodigital, type I52,79,80
Cutaneous pigmentation, dystrophy of the nails, leukoplakia of the oral (305000)
mucosa, continuous lacrimation due to atresia of the lacrimal ducts, often DKC1, Xq28
thrombocytopenia, anemia, testicular atrophy in most cases
Moderate to severe mental retardation, macroorchidism, large ears, (309550)
prominent jaw, high-pitched and jocular speech FMR1, Xq27.3
Clefts of the jaw and tongue, other malformations of the face and skull, (311200)
malformation of the hands and teeth, mental retardation CXORF5, Xp22.3–p22.2

Chromosomal and Other Conditions

47, XXY (Klinefelter)81
49, XXXXY81
Down52,82–86 (190685)
Dyschondrosteosis52,87–89
Tall stature, delayed speech in 50% of the cases, behavior disorders (314240)
Chromosomal
Mild microbrachycephaly, ocular hypertelorism, up-slanting palpebral Chromosomal
fissures, epicanthic folds, strabismus, myopia, low broad nasal bridge,
poorly modeled ears, short neck, taurodontia
Mental retardation, typical facies, heart defects, short stature, dental Trisomy 21
anomalies
Typical deformity of the distal radius and ulna and proximal Pseudo-autosomal
carpal bones, mesomelic dwarfism genes SHOX or SHOXY

5. Saulk JJ Jr, Delaney JR: Taurodontism, diminished root formation and

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defects of the anterior chamber of the eye. Am J Hum Genet 68:364, 2001.
62. Priston M, Kozlowski K, Gill D, et al.: Functional analyses of two newly
identified PITX2 mutants reveal a novel molecular mechanism for
Axenfeld-Rieger syndrome. Hum Mol Genet 10:1631, 2001.
63. Saadi I, Semina EV, Amendt BA, et al.: Identification of a dominant
negative homeodomain mutation in Rieger syndrome. J Biol Chem
276:23034, 2001.
64. Borges AS, Susanna Junior R, Carani JCE, et al.: Genetic analysis of PITX2
and FOXC1 in Rieger Syndrome patients from Brazil. J Glaucoma 11:51,
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65. Gorlin RJ, Goltz RW: Multiple nevoid basal-cell epithelioma, jaw cysts
and bifid rib: a syndrome. New Eng J Med 262:908, 1960.
66. Smyth I, Narang MA, Evans T, et al.: Isolation and characterization of
human Patched 2 (PTCH2), a putative tumour suppressor gene in basal
cell carcinoma and medulloblastoma on chromosome 1p32. Hum Mol
Genet 8:291, 1999.
67. Price JA, Bowden DW, Wright JT, et al.: Identification of a mutation in
DLX3 associated with tricho-dento-osseous (TDO) syndrome. Hum
Mol Genet 7:563, 1998.
68. Price JA, Wright JT, Kula K, et al.: A common DLX3 gene mutation is
responsible for tricho-dento-osseous syndrome in Virginia and North
Carolina families. J Med Genet 35:825, 1998.
69. Ackerman JL, Ackerman AL, Ackerman AB: Taurodont, pyramidal and
fused molar roots associated with other anomalies in a kindred. Am J
Phys Anthropol 38:681, 1973.
70. Heiss NS, Knight SW, Vulliamy TJ, et al.: X-linked dyskeratosis
congenita is caused by mutations in a highly conserved gene with
putative nucleolar functions. Nat Genet 19:32, 1998.
71. Knight SW, Heiss NS, Vulliamy TJ, et al.: X-linked dyskeratosis congenita
is predominantly caused by missense mutations in the DKC1 gene. Am J
Hum Genet 65:50, 1999.
72. Vulliamy TJ, Knight SW, Heiss NS, et al.: Dyskeratosis congenita
caused by a 3-prime deletion: germline and somatic mosaicism in a
female carrier. Blood 94:1254, 1999.
73. Heiss NS, Megarbane A, Klauck SM, et al.: One novel and two
recurrent missense DKC1 mutations in patients with dyskeratosis
congenita (DKC). Genet Couns 12:129, 2001.
74. Knight SW, Vulliamy TJ, Morgan B, et al.: Identification of novel
DKC1 mutations in patients with dyskeratosis congenita: implications
for pathophysiology and diagnosis. Hum Genet 108:299, 2001.
75. Kremer EJ, Pritchard M, Lynch M, et al.: Mapping of DNA instability
at the fragile X to a trinucleotide repeat sequence p(CCG)n. Science
252:1711, 1991.
76. De Boulle K, Verkerk AJMH, Reyniers E, et al.: A point mutation in the
FMR-1 gene associated with fragile X mental retardation. Nat Genet
3:31, 1993.
77. Lugenbeel KA, Peier AM, Carson NL, et al.: Intragenic loss of function
mutations demonstrate the primary role of FMR1 in fragile X syn-
drome. Nat Genet 10:483, 1995.
78. Wang YC, Lin ML, Lin SJ, et al.: Novel point mutation within intron 10
of FMR-1 gene causing fragile X syndrome. Hum Mutat 10:393, 1997.
79. Fenton OM, Watt-Smith SR: The spectrum of the oro-facial-digital
syndrome. Br J Plast Surg 38:532, 1985.
80. Ferrante MI, Giorgio G, Feather SA, et al.: Identification of the gene for
oral-facial-digital type I syndrome. Am J Hum Genet 68:569, 2001.
81. Komatz Y, Tomoyoshi T, Yoshida O, et al.: Taurodontism and
Klinefelter’s syndrome. J Med Genet 15:452, 1978.
82. Down JL: Observations on an ethnic classification of idiots. Clin Lect
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84. Mikkelsen M: Down’s syndrome cytogenetic epidemiology. Hereditas
86:45, 1977.
85. Hook EG: Epidemiology of Down syndrome. In: Down Syndrome.
Advances in Biomedicine and the Behavioral Sciences. Pueschel SM,
Rynders JE, eds. Ware Press, Cambridge, 1982, p 11.
86. Thuline HC, Pueschel SM: Cytogenetics in Down syndrome. In: Down
Syndrome. Advances in Biomedicine and the Behavioral Sciences.
Pueschel SM, Rynders JE, eds. Ware Press, Cambridge, 1982, p 133.
87. Shears DJ, Vassal HJ, Goodman FR, et al.: Mutation and deletion of
the pseudoautosomal gene SHOX cause Leri-Weill dyschondrosteosis.
Nat Genet 19:70, 1998.
88. Grigelioniene G, Eklof O, Ivarsson SA, et al.: Mutations in short stature
homeobox containing gene (SHOX) in dyschondrosteosis but not in
hypochondroplasia. Hum Genet 107:145, 2000.
89. Huber C, Cusin V, Merrer M, et al.: SHOX point mutations in
dyschondrosteosis. J Med Genet 38:323, 2001.
90. Sumiya Y: Statistic study on dental anomalies in the Japanese.
J Anthropol Soc Nippon 67:215, 1959.
91. Merril RG: Occlusal anomalous tubercles on premolars of Alaskan
Eskimos and Indians. Oral Surg Oral Med Oral Pathol Oral Radiol
Endod 17:484, 1964.
92. Yip WK: The prevalence of dens invaginatus. Oral Surg Oral Med Oral
Pathol Oral Radiol Endod 38:80, 1974.
93. Lin LC, Roan RT: Incidence of dens evaginatus investigated from three
junior middle schools at Kaohsiung City. Formosan Sci 34:113, 1980.
94. Hrdlicka A: Shovel-shaped teeth. Am J Phys Anthropol 3:429, 1920.
95. Kannan SK, Suganya, Santharam H: Supernumerary roots. Indian
J Dent Res 13:116, 2002.
96. Kamat SS, Kumar GS, Raghunath V, et al.: Permanent maxillary central
incisor impaction: report of two cases. Quintessence Int 34:50, 2003.
97. Jorgenson RJ, Salinas CF, Shapiro SD: The prevalence of taurodontism
in a select population. J Craniofac Genet Dev Biol 2:125, 1982.
14.6
Dental Malocclusion
Definition
Dental malocclusion consists of teeth that are not properly aligned
in the arch for a reason other than skeletal discrepancy. Maloc-
clusion results from abnormal relationships of the different com-
ponents of the maxillofacial complex. Malocclusion can be of dental
origin or due to skeletal discrepancy. Skeletal malocclusions occur
when the maxilla and/or the mandible are not properly aligned in
relation to the skull or when the maxilla and mandible are mis-
aligned relative to each other. Some malocclusions involve a dental
and skeletal component.
Diagnosis
Dental malocclusion can be diagnosed clinically. It can be asso-
ciated with trauma, caries, oral habits (thumb finger, pacifier),
tooth agenesis, supernumerary teeth, microdontia, macrodontia,
and abnormalities of tooth shape. Dental malocclusion can also
have no apparent cause. Some syndromes with malocclusion have
no other dental anomalies.
Etiology and Distribution
Syndromes with malocclusion as a component are listed in Table
14-15. Dental malocclusion may be caused by genetic and envi-
ronmental factors. In pure ethnic stocks, such as Melanesians of the
Philippine islands, malocclusion is almost nonexistent. However, in
heterogeneous populations, the incidence of jaw discrepancies and
occlusal disharmonies is significantly greater.21 Highest rates of
normal occlusion are reported in British (67.3%), followed by Eu-
ropean descent North-Americans (51%), Lebanese (40.3%), North-
American Indians (34.5%), Egyptians (34.33%), and Swedish (10%).
 Teeth 457

Table 14-15. Syndromes with malocclusion as a component

Causation
Syndrome Prominent Features Gene/Locus

Autosomal Dominant Conditions

Brachydactyly type B11 Involvement of the distal phalanges, nail aplasia, coloboma (113000)
of the macula, characteristic facies, renal agenesis, double ROR2, 9q22
uterus and vagina, mixed hearing loss, high-arched palate,
crowed teeth, supernumerary ribs
Marfan2–10 Increased height; disproportionately long limbs and digits; anterior chest (154700)
deformity; mild to moderate joint laxity; vertebral column deformity FBN1, 15q21.1
(scoliosis and thoracic lordosis); narrow, highly arched palate with
crowding of the teeth
Prader-Willi11–17 Diminished fetal activity, profound poor muscle tone, feeding problems in (176270)
infancy, underdeveloped sex organs, short stature and retarded bone age, Pat del 15q11-q13
small hands and feet, delayed developmental milestones, characteristic facies, Mat UPD 15
cognitive impairment, onset of gross obesity in early childhood due to insatiable
hunger, tendency to develop diabetes in adolescence and adulthood
when weight was not controlled

Autosomal Recessive Conditions

Mannosidosis, Alpha, Susceptibility to infection, vomiting, coarse features, macroglossia, flat nose, large (248500)
lysosomal18–20 clumsy ears, widely spaced teeth, large head, big hands and feet, tall stature, slight MANB
hepatosplenomegaly, muscular hypotonia, lumbar gibbus, radiographic skeletal
abnormalities, dilated cerebral ventricles, lenticular opacities, hypogammaglo-
bulinemia, ‘‘storage cells’’ in the bone marrow, vacuolated lymphocytes in the
bone marrow and blood

However, dental malocclusion rates are higher in Swedish (83%),
followed by North-American Indians (53%), Lebanese (35.5%),
Egyptians (33.3%), European-descent North-Americans (26%), and
British (13.7%). Skeletal discrepancy, which is more influenced by
population mix, is higher in Egyptians (31.6%), followed by Leba-
nese (24.2%), European-descent North-Americans (23%), British
(19%), North-American Indians (10.5%), and Swedish (7%).22–27
No differences between males and females have been noted for
dental malocclusion.27
A relationship exists between certain discrete malpositions of
the permanent canine and tooth agenesis. Studies indicate signifi-
cantly elevated prevalence rates for tooth agenesis in association with
palatally displaced canine, mandibular lateral incisor–canine trans-
position, and maxillary canine–first premolar transposition. Like
tooth agenesis, these three positional anomalies involving the canine
have been reported in families and appear to be under strong genetic
control.28–41 Palatally displaced canine occurs in 1–3% of the pop-
ulation, mandibular lateral incisor–canine transposition in 0.03%,
and maxillary canine–first premolar transposition in 0.25%.42–48
Maxillary canine–first premolar transposition has a higher frequency
in Down syndrome.49 Dental transposition is indicative of faulty
field gene function, which would explain why there is an increased
occurrence of tooth agenesis on either side of transposed teeth. This
may also explain the fact that teeth in the critical marginal areas of
dental lamina, lateral incisors, second premolars, and third molars
are the most vulnerable for tooth agenesis.21 MSX1 and PAX9, which
have been associated with preferential agenesis of posterior teeth,
might be involved in the genetic control of positional anomalies
involving the canine.41,50
Prognosis, Treatment, and Prevention
Dental malocclusion is not a morbid trait. It may pose aesthetic
problems that might lead to lower self-esteem. Other possible con-
sequences are periodontal disease and temporomandibular joint
problems. Orthodontic treatment is recommended and usually
successful. Preventive and interceptive orthodontics is possible and
desirable. Prevention through other techniques is not possible.
References (Dental Malocclusion)
1. Oldridge M, Fortuna AM, Maringa M, et al.: Dominant mutations in
ROR2, encoding an orphan receptor tyrosine kinase, cause brachy-
dactyly type B. Nat Genet 24:375, 2000.
2. Dietz HC, Cutting GR, Pyeritz RE, et al.: Marfan syndrome caused by a
recurrent de novo missense mutation in the fibrillin gene. Nature
352:337, 1991.
3. Hayward C, Keston M, Brock DJH, et al.: Fibrillin (FBN1) mutations
in Marfan syndrome. Hum Mutat 1:79, 1992.
4. Dietz HC, McIntosh I, Sakai LY, et al.: Four novel FBN1 mutations:
significance for mutant transcript level and EGF-like domain calcium
binding in the pathogenesis of Marfan syndrome. Genomics 17:468,
1993.
5. Hewett DR, Lynch JR, Smith R, et al.: A novel fibrillin mutation in the
Marfan syndrome which could disrupt calcium binding of the epidermal
growth factor-like module. Hum Mol Genet 2:475, 1993.
6. Hayward C, Porteous MEM, Brock DJH: Identification of a novel
nonsense mutation in the fibrillin gene (FBN1) using nonisotopic
techniques. Hum Mutat 3:159, 1994.
7. Dietz HC, Pyeritz RE: Mutations in the human gene for fibrillin-1
(FBN1) in the Marfan syndrome and related disorders. Hum Mol
Genet 4:1799, 1995.
8. Hayward C, Brock DJH: Fibrillin-1 mutations in Marfan syndrome
and other type-1 fibrillinopathies. Hum Mutat 10:415, 1997.
9. Hayward C, Porteous ME, Brock DJH: Mutation screening of all 65
exons of the fibrillin-1 gene in 60 patients with Marfan syndrome:
report of 12 novel mutations. Hum Mutat 10:280, 1997.
10. Silva DB, Freitas FCN, Vieira AR, et al.: Sı́ndrome de Marfan:
caracterı́sticas clı́nicas, implicações dentais e relato de caso. J Bras
Odontoped Odonto Bebê 2:230, 1999.
458 Craniofacial Structures
11. Prader A, Labhart A, Willi H: Ein syndrom von adipositas, kleinwuchs,
kryptorchismus und oligophrenie nach myatonieartigem zustand im
neugeborenenalter. Schweiz Med Wschr 86:1260, 1956.
12. Buiting K, Greger V, Brownstein BH, et al.: A putative gene family in
15q11-13 and 16p11.2: possible implications for Prader-Willi and
Angelman syndromes. Proc Nat Acad Sci 89:5457, 1992.
13. Buiting K, Dittrich B, Gross S, et al.: Molecular definition of the
Prader-Willi syndrome chromosome region and orientation of the
SNRPN gene. Hum Mol Genet 2:1991, 1993.
14. Buiting K, Dittrich B, Gross S, et al.: Sporadic imprinting defects in
Prader-Willi syndrome and Angelman syndrome: implications for
imprint-switch models, genetic counseling, and prenatal diagnosis.
Am J Hum Genet 63:170, 1998.
15. Ohta T, Gray TA, Rogan PK, et al.: Imprinting-mutation mechanisms
in Prader-Willi syndrome. Am J Hum Genet 64:397, 1999.
16. Ming JE, Blagowidow N, Knoll JHM, et al.: Submicroscopic deletion in
cousins with Prader-Willi syndrome causes a grandmatrilineal inher-
itance pattern: effects of imprinting. Am J Med Genet 92:19, 2000.
17. Buiting K, Gross S, Lich C, et al.: Epimutations in Prader-Willi and
Angelman syndromes: a molecular study of 136 patients with an imprinting
defect. Am J Hum Genet 72:571, 2003.
18. Nilssen O, Berg T, Riise HMF, et al.: Alpha-mannosidosis: functional
cloning of the lysosomal alpha-mannosidase cDNA and identification
of a mutation in two affected siblings. Hum Mol Genet 6:717, 1997.
19. Gotoda Y, Wakamatsu N, Kawai H, et al.: Missense and nonsense
mutations in the lysosomal alpha-mannosidase gene (MANB) in severe
and mild forms of alpha-mannosidosis. Am J Hum Genet 63:1015,
1998.
20. Berg T, Riise HMF, Hansen GM, et al.: Spectrum of mutations in
alpha-mannosidosis. Am J Hum Genet 64:77, 1999.
21. Mossey PA: The heritability of malocclusion: part 2. The influence of
genetics in malocclusion. Br J Orthod 26:195, 1999.
22. Goose DH, Thomson DG, Winter FC: Malocclusion in schoolchildren
of the west Midlands. Br Dent J 102:174, 1957.
23. Grewe JM, Cervenka J, Shapiro BL, et al.: Prevalence of malocclusion
in Cheppewa Indian children. J Dent Res 47:302, 1968.
24. Ingervall B: Prevalence of dental and occlusal anomalies in Swedish
conscripts. Acta Odontol Scand 32:83, 1974.
25. El-Mangoury NH, Mostafa YA: Epidemiologic panorama of dental
occlusion. Angle Orthod 60:207, 1990.
26. Tipton RT, Rinchuse DJ: The relationship between static occlusion and
functional occlusion in a dental school population. Angle Orthod
16:57, 1991.
27. Saleh FK: Prevalence of malocclusion in a sample of Lebanese school-
children: an epidemiological study. East Mediterr Health J 5:337, 1999.
28. Racek J, Sottner L: Contribution to the heredity of retention of canine
teeth. Cesk Stomatol 77:209, 1977.
29. Peck L, Peck S, Attia Y: Maxillary canine-first premolar transposition,
associated dental anomalies and genetic basis. Angle Orthod 63:99,
1993.
30. Peck S, Peck L, Kataja M: The palatally displaced canine as a dental
anomaly of genetic origin. Angle Orthod 64:249, 1994.
31. Peck S, Peck L: Classification of maxillary tooth transpositions. Am J
Orthod Dentofacial Orthop 107:505, 1995.
32. Peck S, Peck L, Kataja M: Prevalence of tooth agenesis and peg-shaped
maxillary lateral incisor associated with palatally displaced canine
(PDC) anomaly. Am J Orthod Dentofacial Orthop 110:441, 1996.
33. Peck S, Peck L, Kataja M: Site-specificity of tooth agenesis in subjects
with maxillary canine malpositions. Angle Orthod 66:473, 1996.
34. Pirinen S, Arte S, Apajalahti S: Palatal displacement of canine is ge-
netic and related to congenital absence of teeth. J Dent Res 75:1346,
1996.
35. Peck S, Peck L: Palatal displacement of canine is genetic and related to
congenital absence of teeth. J Dent Res 76:728, 1997.
36. Peck S, Peck L, Hirsh G: Mandibular lateral incisor-canine transpo-
sition in monozygotic twins. J Dent Child 64:409, 1997.
37. Sottner L: Our concept of inheritance of tooth retention from the
aspect of molecular biology and genetics. Cesk Stomatol 97:43, 1997.
38. Peck S, Peck L, Kataja M: Mandibular lateral incisor-canine transpo-
sition, concomitant dental anomalies and genetic control. Angle Orthod
68:455, 1998.
39. Plunkett DJ, Dysart PS, Kardos TB, et al.: A study of transposed
canines in a sample of orthodontic patients. Br J Orthod 25:303, 1998.
40. Shapira Y, Kuftinec MM: Maxillary tooth transpositions: characteristic
features and accompanying dental anomalies. Am J Orthod Dentofa-
cial Orthop 119:127, 2001.
41. Peck S, Peck L, Kataja M: Concomitant occurrence of canine malposition
and tooth agenesis: evidence of orofacial genetic fields. Am J Orthod
Dentofacial Orthop 122:657, 2002.
42. Röhrer A: Displaced and impacted canines. Int J Orthod Oral Surg
Radiogr 15:1003, 1929.
43. Dachi SF, Howell FV: A survey of 3874 routine full-mouth radio-
graphs. II. A study of impacted teeth. Oral Surg Oral Med Oral Pathol
Oral Radiol Endod 14:1165, 1961.
44. Niczky E, Müller K, Slavik J: Transposition. Cesk Stomatol 67:227,
1967.
45. Shah RM, Boyd MA, Vakil TF: Studies of permanent tooth anomalies
in 7,886 Canadian individuals. I: impacted teeth. J Can Dent Assoc
44:262, 1978.
46. Järvinen S: Mandibular incisor-cuspid transposition: a survey. J Pedod
6:159, 1982.
47. Sandham A, Harvie H: Ectopic eruption of the maxillary canine
resulting in transposition with adjacent teeth. Tandlaegebladet 89:9,
1985.
48. Hirschfelder U, Petschelt A: Impaction of teeth from an orthodontic
point of view. Dtsch Zahnärztl Z 41:164, 1986.
49. Shapira J, Chaushu S, Becker A: Prevalence of tooth transposition,
third molar agenesis, and maxillary canine impactation in individuals
with Down syndrome. Angle Orthod 70:290, 2000.
50. Vieira AR: Oral clefts and syndromic forms of tooth agenesis as models
for genetics of isolated tooth agenesis. J Dent Res 82:162, 2003.
14.7
Enamel Dysplasia
Definition
Enamel dysplasia is any abnormality of enamel formation. These
defects affect the quality or quantity of enamel and can be divided
into those that are influenced by environmental factors and those
that are idiopathic or genetic in origin. Many environmentally
related factors can contribute to alterations of enamel. These are
listed in Table 14-16.1 Amelogenesis imperfecta (AI) collectively
refers to the group of hereditary enamel malformations that occur
in the absence of a systemic disorder.
Diagnosis
Environmental defects affecting enamel typically manifest as hy-
poplasia, diffuse opacities, or demarcated opacities.1 Since envi-
ronmental factors affect only the teeth that are developing at the
time of the insult, few teeth or only one dentition may be involved.
The affected enamel may be localized or present on many teeth,
with varying degrees of involvement on each affected tooth. He-
reditary dysplasias typically affect all the teeth of both dentitions,
though there are exceptions. A common pattern seen in environ-
mental dysplasias with an insult of short duration is dysplastic,
horizontal bands of enamel. The location of the bands can be
correlated to the stage of tooth development at the time of the
insult and the width to the time interval of the insult. In instances
where genetic dysplasias localize, the resulting defect is in a vertical
direction because of the manner in which amelogenesis occurs
(apex to occlusal direction).2
 Teeth
Table 14-16. Environmental factors associated with
enamel dysplasias1
Systemic
Birth-related trauma
Chemicals
Chromosomal abnormalities
Infections
Inherited diseases
Malnutrition
Metabolic disorders
Neurologic disorders
Local
Local acute mechanical trauma
Electric burn
Irradiation
Local infection
Etiology and Distribution
Natal dysplasia
Horizontal bands of enamel hypocalcification, hypomaturation, or
hypoplasia may be seen across the surfaces of teeth that are devel-
oping at the time of birth: the middle third of the deciduous incisors
and cuspids and the tips of the canines and molars. The trauma of
birth or the physiologic changes that occur at birth are responsible
for these lines. They are most often found in the deciduous dentition
and their presentation is not easily visible. A similar pattern of en-
amel defects involving the cuspids, bicuspids, and second molars
is seen when the traumatic insult occurs around the age of 4 to
5 years.1,3
Ingestional Dysplasia
Severe vitamin D deficiency can cause enamel dysplasia in the typical
horizontal distribution. Ingestion of more than 1.8 parts per million
(ppm) of fluoride in water also causes enamel hypoplasia. While
only 10% of those ingesting 1.8 ppm are affected, 90% of those
ingesting 6 ppm or more are affected. The dysplasia varies from
mottling of the enamel to hypocalcification and hypoplasia. Even
when an entire tooth surface is mottled because of long-term in-
gestion of fluoride, there are superimposed horizontal lines across
the surface that demarcate periods of high and low ingestion.3
Debilitative Dysplasia
Prolonged debilitative disorders are capable of causing a pattern of
enamel dysplasia that is also known as fever hypoplasia. While the
eruptive diseases of childhood most commonly cause debilitative
dysplasia, any serious illness, with or without fever, during the
period of tooth development may do so. The extent of the dysplasia
(width of the dysplastic horizontal line) reflects the duration of the
disease, and the pattern of the dysplasia (number and type of teeth
affected) reflects the approximate age at the time of the disease. The
dysplasia is usually bilateral, as homologous teeth on the left and
right sides are affected equally.
Debilitative diseases with prenatal effect on enamel develop-
ment include congenital syphilis and rubella. Rh incompatibility,
when severe enough to cause erythroblastosis fetalis, may cause
459
enamel dysplasia similar to that of other debilitative diseases or
may cause a general discoloration of the enamel as a consequence of
pigment deposition during amelogenesis.3
Turner Hypoplasia
Trauma to deciduous teeth or periapical inflammation of an
overlying primary tooth may interfere with amelogenesis of suc-
cedaneous teeth. The interference leads to hypoplasia or hypo-
calcification of the enamel of the permanent teeth in a distribution
dependent on the extent of the trauma or infection or on the stage
of development of the permanent tooth. Traumatic dysplasia af-
fects the permanent incisors more often than other teeth, because
injuries to the deciduous incisors are common during childhood.
Infectious dysplasia affects premolars more often than other teeth
because of the frequency of abscesses under deciduous molars.
Permanent molars are least likely to be affected by overlying peri-
apical inflammatory processes since they do not replace a decidu-
ous tooth.3
Hypoplasia Caused by Antineoplastic Therapy
An emerging cause of enamel dysplasia is therapeutic radiation or
chemotherapy used in the treatment for pediatric cancer. The ex-
tent of dysplasia is directly related to the age of the individual at
treatment, the type of therapy administered, and the dose and field
of radiation, if used.1
Amelogenesis imperfecta
AI is a collective term used to describe a group of conditions that
demonstrate developmental alterations in enamel structure without
systemic involvement. Though a number of classification systems
currently exist, the most widely accepted was proposed by Witkop
and Sauk and is based predominantly on the observed phenotype.4
Four major types of AI have been identified based on clinical and
histologic characteristics of enamel: 1) hypoplastic, 2) hypoma-
turation, 3) hypocalcified, and 4) hypomaturation-hypoplastic (Fig.
14-5). This organization scheme is correlated to a disturbance in one
of the phases of amelogenesis: 1) secretion of an organic matrix, 2)
mineralization of the matrix, and 3) maturation of enamel. The four
major groups are subsequently subdivided into 15 subtypes based
primarily on phenotype and, secondarily, by mode of inheritance
(Table 14-17).5
The complexity of the diagnosis for amelogenesis imperfecta
implies genetic heterogeneity. There are currently two genes im-
plicated in the pathogenesis of AI. The first genetic association
was the discovery of the amelogenin gene in the p21.1-22.3 region
of the X chromosome. The second defect was found in the en-
amelin gene on chromosome 4q21. Both of these genes encode
proteins that contribute to the formation of the enamel matrix
during amelogenesis.
As advances are made in determining the genetic etiology of the
various forms of AI, a classification system based on the specific
molecular defect rather than the observed phenotype may emerge.6
To date, seven types of hypoplastic AI have been described.1
They are all characterized by an inadequate deposition of enamel
matrix. Smooth hypoplastic AI may be inherited as an autoso-
mal dominant trait or as an X-linked dominant one. In autosomal
dominant AI, the enamel is thin, smooth, and white and contrasts
with the dentin on radiographs. The teeth are small and somewhat
conical. In the X-linked dominant type, the enamel in males is thin,
smooth, and brown and contrasts with the dentin on X-rays, while
the enamel in females shows alternate vertical bands of normal and
abnormal enamel.
460 Craniofacial Structures

an autosomal dominant and recessive fashion.3 In the autosomal

Fig. 14-5. Amelogenesis imperfecta. A. Intraoral photograph of
patient afflicted with amelogenesis imperfecta. Note the small crown
size of the permanent teeth (arrow) and consequent open contacts
(*). B. Radiograph of the affected teeth, revealing generalized enamel
agenesis on erupted as well as unerupted teeth.
Rough hypoplastic AI is inherited in an autosomal dominant
manner. The enamel is thin, rough, and yellow-brown and con-
trasts with dentin on radiographs.
There are two types of pitted hypoplastic AI. In one type, the
pitting is inherited in an autosomal dominant manner and is
generalized, although vertical orientation of the pits may be seen
and the labial surfaces are more frequently pitted than the lingual
surfaces. In the other type, the pitting is limited to the middle
third of the crown and is distributed horizontally. This pattern of
localized pitting has been characterized in cases inherited in both
recessive enamel agenesis pattern, there is a total lack of enamel
formation. The surface of the dentin is rough and an anterior
open bite is occasionally seen.1
In hypomaturation AI, the deposition and initial mineraliza-
tion of the enamel matrix is normal. There is, however, a defect in the
maturation of the enamel structure.1 To date, four types of hypo-
maturation AI have been described. Pigmented hypomature AI may
be inherited as an autosomal recessive or an X-linked recessive trait.
The enamel in males with either type is normally thick, yellow-
brown, and soft and does not contrast with the dentin on radio-
graphs. The enamel in females with the autosomal recessive form is
identical to that in males. By contrast, X-linked recessive form in
females shows alternate vertical bands of normal and hypomature
enamel. Localized hypomature AI, typically inherited as an autoso-
mal dominant trait, is believed to also occur as an X-linked trait.1 It is
characterized by white, opaque enamel over the incisal and occlusal
two-thirds of the teeth. The distribution of the defect is horizontal,
contrary to the normal vertical distribution observed in other genetic
dysplasias, leading to the descriptive term snow-capped teeth.3
In the hypocalcified form of AI, the enamel matrix is deposited
normally but fails to mineralize to any significant extent.1 Two
types of hypocalcified AI have been identified. One is inherited as
an autosomal dominant trait, and the other as autosomal recessive.
The enamel of both types is normally thick, yellow-brown and
friable and appears moth-eaten on radiographs.3
The hypomaturation/hypoplastic form of AI demonstrates both
enamel hypoplasia and hypomaturation. Though the two identified
patterns are similar, they are differentiated by the thickness of enamel
and the overall tooth size. The hypomaturation/hypoplastic pattern is
characterized by enamel hypomaturation, where the enamel appears
mottled yellow-white to yellow-brown. This is accompanied by
varying degrees of taurodontism. The hypoplastic/hypomaturation
form of AI has thin enamel as a hallmark feature and also demon-
strates hypomaturation.1
AI affects approximately one in 1500 Americans of Caucasian
background, with autosomal dominant hypocalcified AI account-
ing for 40% of all cases. While the frequency of AI among Amer-
icans of other racial backgrounds has not been reported, there is no

Table 14-17. Classification of amelogenesis imperfecta5

Type Pattern Specific Features Inheritance Genetic Defect

IA Hypoplastic Generalized pitted AD Unknown

IB Hypoplastic Localized pitted AD (104500) Enamelin (ENAM)
IC Hypoplastic Localized pitted AR (204650) Unknown
ID Hypoplastic Diffuse smooth AD (104500) Enamelin (ENAM)
IE Hypoplastic Diffuse smooth XLD (300391) Amelogenin(AMELX)
IF Hypoplastic Diffuse rough AD Unknown
IG Hypoplastic Enamel agenesis AR Unknown
IIA Hypomaturation Diffuse pigmented AR (204700) Unknown
IIB Hypomaturation Diffuse XLR (301100) Amelogenin (AMELX)
IIC Hypomaturation Snow capped X-linked Unknown
IID Hypomaturation Snow capped AD Unknown
IIIA Hypocalcified Diffuse AD Unknown
IIIB Hypocalcified Diffuse AR Unknown
IVA Hypomaturation-hypoplastic Taurodontism AD (104510) Unknown
IVB Hypoplastic-hypomaturation Taurodontism AD Unknown
 Teeth 461

Table 14-18. Syndromes with enamel dysplasia as a feature3

14.8
Syndrome Dysplasia Type
Dentin Dysplasia
Autosomal Dominant Conditions
Amelo-onycho-hypohidrotic Hypocalcification/hypoplasia Definition
Oculodentoosseous dysplasia Hypoplasia Dentin dysplasia is an abnormal formation of dentin. The dysplasia
Trichodentoosseous Hypocalcification/hypoplasia may manifest in the absence of a systemic disorder or in con-
Tuberous sclerosis Pitted hypoplasia
junction with other anomalies and have either an environmental or
genetic origin. Environmentally induced dentin dysplasias include
EEC Hypoplasia
pigmentary and physiologic dysplasia. Dentinogenesis imperfecta
Ectodermal dysplasia, Basan type Hypocalcification (DI) refers to one of the inherited dentin dysplasias that presents
without a systemic component. This includes types I and II dentin
Autosomal Recessive Conditions
dysplasia; DI types I, II, and III; pulpal dysplasia; and fibrous
Morquio syndrome (MPS-IV) Hypoplasia
dysplasia of the dentin.
Vitamin D–dependent rickets Rough hypoplasia
Kohlschutter Hypoplasia Pigmentary Dysplasia
McGibbon Aplasia Pigmentary dysplasia can be seen clinically because of the trans-
Epidermolysis bullosa (AR type) Pitted hypoplasia lucent nature of the overlying enamel. Erythropoietic porphyria
causes red-brown discoloration of the teeth; in primary teeth the
X-Linked Conditions pigmentation (porphyrin deposition) may involve all layers,
Amelocerebrohypohidrotic Hypoplasia
whereas in permanent teeth the pigmentation is predominantly in
Pseudohypoparathryoidism Pitted hypoplasia the dentin and cementum. Erythroblastosis fetalis (hemolytic dis-
Focal dermal hypoplasia Hypoplasia ease of the newborn) causes yellow-green pigmentation; again, the
enamel may be affected, but the heaviest pigmentation (deposition
of hemolyzed fetal blood products) is in the dentin. Tetracycline
causes a yellow to yellow-brown discoloration of dentin. Agents
and compounds that may discolor fully formed teeth include silver
evidence that it differs greatly from that among Caucasians. Enamel amalgam (black), copper (blue-green), nickel and chromium
dysplasia is also seen as a component of many syndromes of genetic (green), lead (brown), bismuth (gray-blue), oil of cloves (brown-
and environmental origin. These are summarized in Table 14-18.3 black), bilirubin (green), hemin and hematin (blue-black), met-
hemoglobin (red-brown), and hematoidin (orange). Physiologic
Prognosis, Treatment, and Prevention processes through which fully formed teeth may become discolored
Enamel dysplasia, while not inconsequential, has a generally good include internal resorption (pink), pulp disease (gray-black), and
prognosis. Other tooth layers are not affected, and the teeth can be dental caries (color dependent on staining agent to which dentin is
maintained for a lifetime. Whether it is environmental or genetic exposed).
in etiology, enamel dysplasia is easily and successfully treated,
albeit the necessary restorative dentistry may be expensive. Seal- Physiologic Dysplasia
ants, composite restorations, crowns, and other restorative tech- Most physiologic dysplasias are seen as exaggerated develop-
niques work well and are used interchangeably, depending on the mental lines on histologic sections.
site and extent of the dysplasia.3
Enamel dysplasia of environmental origin can be prevented by
Dentinogenesis Imperfecta
avoiding the known cause. Enamel dysplasia of genetic origin can
be dealt with through genetic counseling. While most couples may The types of DI (Table 14-19) can be differentiated by clinical and
not modify family planning because of a risk for AI, some will; radiographic features (Fig. 14-6). In classical DI (DI-IA), the teeth
those who do not can be alerted through counseling of the risks so are yellow-brown to blue-gray in color and appear translucent.
that prognosis is improved by early diagnosis and treatment.3 The crowns are bulbous because of an exaggerated constriction at
the cementoenamel junction. The pulp chambers of some primary
References (Enamel Dysplasia) teeth and all secondary teeth are obliterated by atypical dentin.
1. Neville BW, Damm DD, Allen CM, et al.: In: Oral and Maxillofacial The obliteration is progressive, beginning before eruption and
Pathology, ed 2. WB Saunders Company, Philadelphia, 2002, p 49. continuing afterwards. The roots are excessively tapered and
2. Jorgensen RJ, Yost C: Etiology of enamel dysplasias. J Pedodontol foreshortened. Histopathologic studies reveal (1) absence of ex-
6:315, 1982. tensions of dentinal tubules into the enamel, (2) smooth (not
3. Jorgenson RJ: Teeth. In: Human Malformations and Related Anomalies, scalloped) dentin-enamel junctions, and (3) abnormal dentinal
ed 1. Stevenson RE, Hall JG, Goodman RM, eds. Oxford University tubules.
Press, New York, 1993, p 383. In DI-IB, the teeth are also yellow-brown to blue-gray in color
4. Witkop CJ, Sauk JJ: Heritable defect of enamel. In: Oral Facial
and appear translucent. Crown shape is like that of DI-IA, but the
Genetics. RE Stewart, GH Prescott, eds. CV Mosby, St. Louis, 1976,
pulp chambers of primary teeth, rather than being obliterated, are
p 151.
5. Witkop CJ: Amelogenesis imperfecta, dentinogenesis imperfecta and excessively large. There is very little dentin, with most of the pulplike
dentin dysplasia revisited: problems in classification. J Oral Pathol inner portion of the teeth consisting of coarse collagen bundles.
17:547, 1988. In DI-II, also called radicular dentin dysplasia or rootless teeth,
6. Aldred MJ, Savariarayan R, Crawford PJM: Amelogenesis imperfecta: a the crowns are normal in color and shape. The pulp chambers are
classification and catalogue for the 21st century. Oral Dis 9:19, 2003. virtually obliterated, but there are crescent-shaped radiolucencies in
462 Craniofacial Structures

Table 14-19. Classification of dentinogenesis imperfecta (DI)1–3

Type Features Alternative Classification Genetic Defect

IA Obliterated appearance, obliterated pulps, Shields II (125420) Dentin sialo-phosphoprotein

exaggerated coronal constriction (DSPP)
IB Similar to IA, but pulp chambers of DI Brandywine type, Shields III Likely dentin matrix acidic
deciduous teeth are enlarged (125500) phospho-protein-1 (DMP1)
II Obliterated pulp (crescent-shaped Dentin dysplasia I (125400) Unknown
radiolucencies), foreshortened roots,
premature loss of teeth
III Opalescence of deciduous teeth, Dentin dysplasia II, pulpal Dentin sialo-phosphoprotein
thistle-tube pulp chambers dysplasia (125420) (DSPP)
IV Obliterated pulps, fibrous dentin Fibrous dysplasia of dentin Unknown

the central portions of the teeth. The roots are virtually absent,
leading to premature ‘‘loosening’’ and loss of teeth. There are also
multiple periapical radiolucencies around most roots. Histopatho-
logic studies reveal that, in fact, the pulp is absent, having been
replaced by regularly formed, eumorphous concretions.
In DI-III, also termed coronal dentin dysplasia, the color of
the crowns of the primary teeth resembles that of DI-I, but the
crowns of the secondary teeth are normal in color and shape. On
radiographs the pulp chambers of affected teeth resemble the
Fig. 14-6. Dentinogenesis imperfecta (DGI). A. Intraoral photograph
of patient afflicted with DGI. Note the discoloration and extensive
loss of tooth structure. B. Radiograph of the affected teeth, revealing
bulbous crowns, obliterated pulp chambers, and narrowed root canals.
(Courtesy of Dr. Nadarajah Vigneswaran, University of Texas Health
Science Center, Houston, TX.)
thistle-tube glassware used in chemistry laboratories. Roots are
well formed, and there is seldom premature tooth loss.
In DI-IV, the crowns of teeth are also normal in size and
shape, as are the pulp chambers, but pulpal tissue is obliterated by
atypical dentin, and the dentin itself is abnormal in histopatho-
logic study.
Etiology and Distribution
DI-I is a relatively common disorder, affecting approximately one in
8000 individuals. It has recently been linked to mutations in the
dentin sialophosphoprotein (DSPP) gene on chromosome 4q21.4
The gene product is cleaved into two dentin-specific matrix proteins,
dentin sialoprotein (DSP) and dentin phosphoprotein (DPP). DPP,
a highly acidic protein, is the major noncollagenous component of
dentin, being solely expressed by the ectomesenchymal-derived
odontoblast cells of the tooth. Unique to all of the reported cases of
DI-I, all patients have a positive family history (have affected pro-
genitors), and all patients whose ancestry can be traced are des-
cended from the population in a particular province in France.
DI-IA is inherited as an autosomal dominant trait, with vir-
tually complete penetrance and remarkably little variation in ex-
pression. Variation is so minimal, in fact, that its occurrence (e.g.,
enlarged pulp chambers of primary teeth) is evidence that favors
the existence of DI-IB. DI-IB is largely limited to a triracial isolate
in the United States, although it has recently been reported among
Ashkenazi Jews. Linkage analysis revealed the most likely candidate
gene for DI-IB in a branch of the Brandywine kindred was dentin
matrix acidic phosphoprotein-1.5 These results again were con-
sistent with the hypothesis that DI-I and DGI-III are allelic or the
result of mutations in two tightly linked genes, DSPP and DMP1.
DI-II is more rare than DI-I, occurring in only one in
100,000 persons. The mutation rate for the DI-II gene seems low
and clinical variation is minimal. While the primary defect is
unknown, it has been suggested that the epithelial component of
the root sheath invaginates too early in development and causes
root aplasia.
DI-III is less common than the other dentin dysplasias,
having been reported in only a few families. It is an autosomal
dominant disorder in which mineralization of the dentin of the
primary teeth is abnormal. On the basis of the phenotypic overlap
and shared chromosomal location with dentinogenesis imperfecta
type I, it has been proposed that the two conditions are allelic. A
missense mutation (encoding an aspartic acid to tyrosine change)
was reported in DSPP in a family with dentin dysplasia type II.6
The substitution in the hydrophobic signal peptide domain
caused a failure of translocation of the encoded proteins into the
 Teeth
endoplasmic reticulum. It is hypothesized that this would likely
lead to a loss of function of both DSP and DPP.
DI-IV is the rarest of the dentin dysplasias, having been re-
ported in a single family as an autosomal dominant trait. The
primary defect underlying this disorder is unknown.
Prognosis, Treatment, and Prevention
Individuals affected by DI-I are prone to lose teeth because the in-
herent weakness at the dentin-enamel junction causes the enamel to
fracture, thereby exposing the more delicate, underlying dentin to
occlusal forces and cariogenic agents. Any treatment that protects the
dentin should prove effective. Stainless steel crowns and other types
of full crown coverage are adequate. Dental restorations, such as
amalgam fillings and gold inlays, are likely to fail. Individuals with DI-
II lose their teeth because excessive mobility leads to periodontal
disease or exfoliation. Short of extractions and prostheses, treatment is
not effective. DI-III and DI-IV do not predicate the loss of teeth.
Prevention is possible only through family planning by affected in-
dividuals.
References (Dentin Dysplasia)
1. Shields ED, Bixler D, EI-Kafrawy AM: A proposed classification for
heritable human dentine defects with a description of a new entity.
Arch Oral Biol 18:543, 1973.
2. Jorgenson RJ: Problems in nomenclature of craniofacial disorders.
J Craniofac Genet Dev Biol 9:7, 1989.
3. Jorgenson RJ: Teeth. In: Human Malformations and Related Anom-
alies. Stevenson RE, Hall JG, Goodman RM, eds. Oxford University
Press, New York, 1993, p 383.
4. Patel PI: Soundbites. Nat Genet 27:129, 2001.
5. MacDougall M, Jeffords LG, Gu TT, et al.: Genetic linkage of the
dentinogenesis imperfecta type III locus to chromosome 4q. J Dent Res
78:1277, 1999.
6. Rajpar MH, Koch MJ, Davies RM, et al.: Mutation of the signal peptide
region of the bicistronic gene DSPP affects translocation to the
endoplasmic reticulum and results in defective dentine biomineralization.
Hum Mol Genet 11:2559, 2002.
14.9
Cementum Dysplasia
Cementum dysplasia is a neoplastic disease that is described here
because it is relatively common and its neoplastic nature is not al-
ways recognized at discovery. At the time of discovery, cementum
dysplasia often resembles hypercementosis or fibrous dysplasia of
the adjacent alveolar bone. Cementum is the most poorly under-
stood layer of the teeth. Nonetheless, three entities should be men-
tioned here: concrescence, familial cementoma, and cementum
dysplasia.
Concrescence is simply the fusion of adjacent teeth by ce-
mentum only. Concrescence is probably caused by nothing more
than close approximation of the roots of developing teeth. Its
frequency in the population has not been well-established. Fa-
milial cementomas are neoplastic lesions that appear in all four
quadrants, a combination that is thought to be inherited as an
autosomal dominant trait. Only a few families have been reported.
Cementum dysplasia is a neoplastic process that is found in two to
three individuals per 1000 in the general population. Females are
more commonly affected than males and blacks more commonly
than whites. Mandibular anterior teeth are more commonly af-
fected than other teeth.
463
Each of these disorders is benign, requires no treatment, and
cannot be prevented. Each may complicate extraction of affected
teeth that have to be removed for other reasons.1
Reference (Cementum Dysplasia)
1. Jorgenson RJ: Teeth. In: Human Malformations and Related Anom-
alies. Stevenson RE, Hall JG, Goodman RM, eds. Oxford University
Press, New York, 1993, p 383.
14.10
Abnormalities of Tooth Eruption
Definition
Abnormalities of tooth eruption can be early, delayed, or a lack
of tooth eruption. All of these conditions can manifest indepen-
dently or as a component of an underlying disorder. The nor-
mal eruption sequence for each tooth is shown in Tables 14-1A
and 14-1B.
Ordinarily, the deciduous teeth erupt between ages 6 months
and 2 years in the following sequence: incisors, 6 to 9 months; first
molars, 12 to 14 months; canines, 16 to 18 months; and second
molars, 20 to 24 months. The permanent teeth ordinarily erupt
between ages 6 and 21 years in the following sequence: first molars
and lower central incisors, 6 to 7 years; lower lateral incisors, 7 to 8
years; upper lateral incisors, 8 to 9 years; lower canines, 9 to 10
years; premolars, 10 to 12 years; upper canines, 11 to 12 years;
second molars, 12 to 13 years; and third molars, 17-21 years. Small
variations from these eruption patterns are common and may even
be familial. Teeth in females generally erupt earlier than those
in males.
Natal Teeth
Natal teeth are those that are present at birth or erupt within the first
month. While natal teeth are most commonly lower central incisors,
other teeth may erupt early or the natal teeth may be supernumer-
ary (predeciduous). Natal teeth may be inherited in an autosomal
dominant fashion.1 They occur in roughly one in 3000 newborns.2
Natal teeth are found in cyclopia, Ellis-van Creveld syndrome,
Hallermann-Streiff syndrome, pachyonychia congenita, Pallister-
Hall syndrome, short rib-polydactyly type II, and Wiedemann-
Rautenstrauch syndrome.
Eruption Delays or Impaction
Developmental delays in tooth eruption are most commonly at-
tributed to mechanical interferences caused by supernumerary teeth,
crowding, soft tissue impaction, or odontogenic tumors and cysts.
Ankylosis typically occurs after partial eruption of the tooth into the
oral cavity; it is defined as the fusion of cementum or dentin to
alveolar bone due to cellular changes in the periodontal ligament
caused by trauma and other pathologies. When the tooth becomes
ankylosed, it appears to submerge in relation to adjacent teeth that
continue to erupt. Eruption failure and delayed eruption are con-
ditions that do not naturally involve ankylosis and are associated
with craniofacial dysostosis, hypothyroidism, hypopituitarism and
several genetic and medical syndromes.3–6 Eruption defects can also
present as a component of various syndromic conditions and are
summarized in Table 14-20.
Primary failure of eruption (PFE) is characterized by a lo-
calized failure of eruption of permanent posterior teeth and lacks
any systemic involvement. The affected teeth are nonimpacted,
464 Craniofacial Structures

nonankylosed, and fully formed, but are unable to reach the oc-
clusal plane presumably due to a primary defect in the eruption
mechanism itself. Attempts to close the resultant ‘‘open bite’’
orthodontically often result in ankylosis of PFE-affected teeth.7
(Fig. 14-7)
Prognosis, Treatment, and Prevention
Most natal teeth are firmly imbedded and pose no risk to the neo-
nate. Those that are loose should be extracted to avoid aspiration.
Delayed eruption can have considerable consequence on ultimate

Table 14-20. Syndromes with tooth eruption defects as a feature6

Causation
Syndrome Eruption Phenotype Gene/Locus

Cleidocranial dysplasia Delayed eruption AD (600211)

RUNX2/CBFA1, 6p21
Osteopetrosis Failure of eruption AR and AD
TRAF6
GAPO Failure of eruption AR
Osteopathia striata with cranial sclerosis Failure of eruption in some cases AD
Osteoglophonic dysplasia Failure of eruption of 28 teeth AD
Singleton-Merten Dysplastic development with AD possibly
delayed eruption of 28 teeth
Aarskog Delayed eruption XLR (305400)
FGDY1, Xp21.1
Acrodysostosis Delayed tooth eruption AD (101800)
(23% of cases)
Albright hereditary osteodystrophy Delayed eruption AD (103580)
GNAS, 20q13.2
Apert Delayed and ectopic eruption AD (101200)
FGFR2
Chondroectodermal Delayed eruption and AR (225500)
dysplasia (Ellis–van Creveld) partial anodontia Several mutations
in the EVC gene
Cockayne Delayed eruption AR
CSB (ERCC6)
gene (helicase)
De Lange Delayed eruption AD
NIPBL, 5p13.1
Dubowitz Delayed eruption and hypodontia AR possibly
Frontometaphyseal Delayed eruption and retained deciduous AD (304120)
dysplasia (Gorlin-Cohen) teeth FLNA, Xq28
Goltz (Focal dermal hypoplasia) Delayed eruption and hypodontia XLD, lethality in
with hypoplastic teeth hemizygous males
Hunter Delayed eruption XL (309900)
IDS, Xq28
Incontinentia pigmenti Delayed eruption and XLD, lethality in males
hypodontia in 80% NEMO, Xq28
heterogeneous
Killian/Teschler-Nicola Delayed eruption Mosaic tetrasomy
12p in skin fibroblasts
Levy-Hollister Delayed eruption of 18 teeth AD
Maroteaux-Lamy mucopoly- Delayed eruption with small teeth AR (253200)
saccharoidosis (MPS VI) ASB, 5q11–q13
Osteogenesis imperfecta, type I Delayed eruption and dysplastic teeth AD
COL1A1, COL1A2
Progeria (Hutchinson-Gilford) Delayed eruption of 18 and 28 AR (176670)
teeth and hypodontia of 28 teeth LMNA, 1q21.2
Pyknodysostosis Delayed eruption and occasional anodontia AR (265800)
CTSK, 1q21
Primary failure of eruption* Failure of 28 teeth to erupt partially or
completely

*Not associated with overt systemic disease.

 Teeth 465

occlusion. The choices of treatment for impacted teeth include long-

term observation, orthodontically assisted eruption, transplantation,
or surgical removal. The presence of infection, nonrestorable carious
lesions, cysts, tumors, or destruction of adjacent teeth necessitates
surgical removal of the affected teeth.8 None of the conditions af-
fecting tooth eruption is preventable.

References (Abnormalities of Tooth Eruption)

1. Bodenhoff J, Gorlin RJ: Natal and neonatal teeth; folklore and fact.
Pediatrics 32:1087, 1963.
2. Jorgenson RJ, Shapiro SD, Salinas CF, et al.: Intraoral findings and
anomalies in neonates. Pediatrics 69:577, 1982.
3. Sauk JJ: Genetic disorders involving tooth eruption anomalies. In: The
Biological Mechanisms of Tooth Eruption and Root Resorption.
Davidovitch Z, ed. EBSCO Media, Birmingham, 1988, p 171.
4. Gorlin RJ, Cohen MM, Levin LS: Syndromes of the Head and Neck,
ed 3. Oxford University Press, New York, 1990.
5. Jones KL: Smith’s Recognizable Patterns of Human Malformation,
ed 5. WB Saunders Company, Philadelphia, 1997.
6. Wise GE, Frazier-Bowers S, D’Souza RN: Cellular, molecular, and
genetic determinants of tooth eruption. Crit Rev Oral Biol Med 13:323,
2002.
7. Proffit WR, Vig KW: Primary failure of eruption: a possible cause of
posterior open-bite. Am J Orthod 80:173, 1981.
8. Neville BW, Damm DD, Allen CM, et al.: Oral and Maxillofacial
Pathology, ed 2. WB Saunders Company, Philadelphia, 2001, p 49.

Fig. 14-7. Primary failure of eruption. Intraoral photograph (A),

dental models (B), and panoramic radiograph (C) showing nonanky-
losed, submerged upper left posterior quadrant and resulting posterior
lateral open bite (arrows).