Wright 2000
Wright 2000
Wright 2000
OO
From the Department of Pediatric Dentistry, School of Dentistry, The University of North
Carolina, Chapel Hill, North Carolina
b
PEDIATRIC CLINICS OF NORTH AMERICA
TOOTH DEVELOPMENT
occur, then teeth do not form. This fact has been proven experimentally
in transgenic mice, in which transcription factors, such as M S X l and
MSX2, were knocked out, after which no teeth developed.40
After tooth formation has been initiated by the invagination of the
oral epithelium, the ectodermal cells and the underlying ectomesenchy-
ma1 cells engage in a complex series of interactions and signaling mecha-
nisms. Instructive biochemical messages regulating cell proliferation,
differentiation, and matrix production are transmitted between the ecto-
dermal and mesenchymal cells. These interactions result in the differenti-
ation of highly specialized cells that produce the unique dental tissues
and establish the tooth size and shape. The location and type of tooth
(e.g., incisor, cuspid, premolar, or molar) are thought to be genetically
determined by the differential combinatorial expression of transcription
factors in the regions of the developing teeth.%The oral epithelium gives
rise to the enamel organ, which differentiates into the enamel-forming
cells, called ameloblasfs. The ectomesenchymal cells give rise to the odon-
toblasts, which form the dentin and pulp. The tooth root surface eventu-
ally is covered by cementum, which is formed by cementoblasts, which
are derived from the mesenchyme. For an intact and viable tooth to
develop, each of these cell types must differentiate, produce and process
a unique extracellular matrix, and regulate mineralization of the extracel-
lular matrix. All of these processes involve strict genetic control, so
they represent potential pathways for hereditary defects of teeth, as is
discussed later. Numerous excellent and detailed reviews on the mo-
lecular control and mechanisms of normal tooth development are avail-
able.40.60,61.68
Teeth are multifunctional appendages participating in diverse func-
tions, such as eating and speech. The human dentition also has a crucial
role in facial esthetics, so it is important in complex human socialization
processes. Dentition provides an efficient masticatory system that allows
incising, tearing, and grinding of food. The unique composition and
structure of the teeth allows them to survive the tremendous forces
and wear associated with mastication. Alteration of the composition or
NORMAL FORMATION AND DEVELOPMENT DEFECTS OF HUMAN DENTITION 977
DENTAL TISSUES
Enamel
Dental enamel is the hardest tissue in the human body and provides
the fracture-resistant and wear-resistant outer covering for the tooth
crown. Enamel is produced by ameloblasts, which secrete a unique
extracellular matrix; process this matrix; control the mineralization pro-
cess; protect the formed enamel during tooth eruption; and then become
a part of the epithelial attachment of the tooth to the gingiva.60Enamel
has no regenerative capacity because the ameloblasts are no longer
present in the fully formed and erupted tooth. Although the enamel is
initially deposited as an organic matrix, it mineralizes by the tightly
controlled processing of the extracellular matrix and regulation of cal-
cium and phosphate mineral deposition.x Defects in the enamel extracel-
lular matrix or its processing may lead to enamel formation that is
deficient (hypoplastic) or hyp~mineralized.~~ Fully developed enamel
consists primarily of carbonate-substituted hydroxyapatite mineral that
is highly organized into a unique structure. The apatite molecules are
organized into crystallites, which are then arranged and oriented into
interlocking prisms (Fig. 1). This complex and highly ordered structure
helps to give enamel its incredible strength and wear resistance. Healthy
enamel is approximately 96% mineral by weight with about 2% water,
1% protein, and 1% other component^.^^ Alterations in the mineral
composition, such as substituting fluorine for carbonate, markedly de-
crease the acid solubility of the Changes in the mineral, water,
or protein content of enamel result in alteration of the clinical appear-
ance, strength, dental caries, and wear resistance of the tissue. Healthy
enamel is highly translucent, so much of the color of teeth is derived
from the underlying dentin and pulp.
Dentin
Figure 2. Odontoblastic processes are seen entering the dentinal tdbules in normal human
dentin (scanning electron micrograph, original magnification x 2000).
NORMAL FORMATION AND DEVELOPMENT DEFECTS OF HUMAN DENTITION 979
Pulp
The dental pulp is a specialized tissue comprised of a layer of
odontoblasts, fibroblasts, blood vessels, nerves, and a complex extracel-
lular matrix. The pulp provides the reparative potential of teeth and
neurosensory functi0n.4~The dental pulp can increase the production of
dentin (reparative dentin) in an attempt to protect and wall off the vital
pulp tissue from injury or noxious stimuli.71Prompt treatments of dental
trauma and dental caries are critical steps toward maintaining a healthy
vital pulp and allowing an injured or diseased tooth to retain a vital
pulp. The pulp continues to lay down small amounts of dentin through-
out the life of teeth as a part of the normal pulp physiology.64This
process results in a smaller pulp chamber as people age and is part of
the reason that teeth continue to yellow with age. It is critical to maintain
a healthy dental pulp until the root is fully formed and its walls are of
adequate thickness to maintain the tremendous forces transmitted from
the crown during function. If the pulp becomes nonvital in a young tooth
that lacks complete root formation, successful completion of endodontic
treatment is much more difficult, and the likelihood of retaining the
tooth is diminished.
Cementum
Cementum is a unique tissue that covers the root surface and helps
to prevent teeth from becoming fused to, or resorbed by, the adjacent
alveolar bone. Cementum also provides the tissues by which each tooth
is anchored by a fibrous network, the periodontal ligament, to the
alveolar bone of the jawss3 To perform this specialized attachment
function, cementum is comprised of type 1 and other collagens, noncol-
lagenous proteins, and a mineralized matrix. The combined organic and
mineralized components of cementum allow fibers from the periodontal
ligament to insert into, and be held by, the cementum. Together, the
cementum, periodontal ligament, and alveolar bone produce a complex
attachment system that works as a flexible sling that holds the tooth in
place while allowing normal physiologic movement under the tremen-
dous masticatory loads placed on the dentition. All three of these tissues
can regenerate, allowing traumatized teeth (e.g., tooth avulsion) or ab-
normalities (e.g., periodontal disease) to be treated s~ccessfully.5~ A
comprehensive discussion of injury and treatment is included in the
article by McTigue later in this issue.
980 WRIGHT
35
30
25
10
0
Central Lateral Canine First Second
incisor incisor molar molar
Figure 3. Age and variability of normal primary tooth eruption. Hatched bar = mandibular;
solid bar = maxillary. (Data from Lunt RC, Law DB: A review of the chronology of
calcification of deciduous teeth. J Am Dent Assoc 89:872-879, 1974.)
NORMAL FORMATION AND DEVELOPMENT DEFECTS OF HUMAN DENTITION 981
20
18
16
14
12
h
x
v
a, 10
2
8
0
Central Lateral Canine First Second First Second Third
Incisor Incisor Premolar Premolar Molar Molar Molar
Figure 4. Age of normal permanent took eruption. Hatched bar = mandibular; solid bar
= maxillary. (Data from McDonald RE, Avery DR: Eruption of the teeth: Local, systemic
and congenital factors that influence the process. In McDonald RE, Avery DR (eds):
Dentistry for the Child and Adolescent, ed 5. St. Louis, Mosby, 1987, p 190.)
Figure 5. This radiograph of a newborn with natal teeth confirms they are the normal
primary central incisors and not supernumerary teeth.
982 WRIGHT
tion times exist.19Some reports show that black people have earlier tooth
eruption compared with white people.21Normally, the eruption of teeth
is bilaterally symmetric, with the left and right antimeres erupting at
similar times. Children deviating markedly from normal tooth eruption
chronology (>6 mo _t normal deviation) or symmetry should be evalu-
ated for abnormal dental eruption or congenitally missing teeth. A
generalized delay in the timing of tooth eruption can be familial or
occur in patients with conditions such as Down syndrome.12Complete
failure of tooth eruption is associated with various conditions that can
be localized (e.g., isolated to an individual tooth), generalized, or associ-
ated with a ~yndrome.~'
Figure 6. The result of untreated early ankylosis of the second primary molar that resulted
in severe submergence of the primary teeth and displacement of the permanent premolar
(arrows).
984 WRIGHT
thin and lack sufficient structure for periodontal fiber insertion, resulting
in premature tooth 1 0 ~ sIn . ~children with hypophosphatasia, primary
Figure 8. Eruption of the permanent mandibular incisors behind the primary incisors is not
infrequent because of the lingual position of the developing permanent incisor to the
mandibular incisor tooth root.
Table 1. CONDITIONS ASSOCIATED WITH PREMATURE PRIMARY TOOTH EXFOLIATION
Condition Oral Manlfestatlons Systemic Manifestations Cause
Hypophosphatasia Tooth loss as early as 1 year of age, Decreased alkaline phosphatase, severe Autosomal dominant and recessive
(OMM 146300 & 241500) minimal soft-tissue cases can have bone manifestations, forms, mutations in tissue
inflammation, large dental pulp bowing of legs, short stature nonspecific alkaline phosphatase
chambers, variable enamel gene
hypoplasia
Papillon LeFevere Tooth loss beginning 2nd to 3rd Hyperkeratosis of palmar and plantar Autosomal recessive trait,
syndrome (OMM year of life, marked soft-tissue surfaces mutation in cathepsin gene
245000) inflammation, generalized
alveolar bone loss
Cyclic neutropenia Severe erythematous gingivitis, can Recurrent fevers, malaise, sore throat, Autosomal dominant trait, defect
(OMIM 162800) have rapid periodontal anorexia, 21-day periodicity of in neutrophil elastase
breakdown and bone loss decreased neutrophils
Chediak Higashi syndrome Ulcerations of oral mucosa, severe Partial albinism, neutropenia, recurrent Autosomal recessive trait,
(Oh4JM 214500) gingivitis, glossitis, periodontal infections of skin and respiratory ’ deficiency of natural killer
breakdown and bone loss tract, frequently lethal before age 7 y lymphocytes
Langerhans’ cell Ulcerative gingivitis, root exposure Bone Iksions, multiorgan involvement, Proliferation of Langerhans’ cells
histiocytosis and premature tooth mobility seborrheic scalp rash, diabetes (dendritic histiocytes),
(Histiocytosis X) typically starting with posterior insipidus, growth retardation immunologic dysregulation
teeth
Prepubertal periodontitis Variable gingival inflammation Autosomal dominant trait,
(OMIM 170650) (localized minor to generalized leukocyte defect involving
severe), alveolar bone loss chemotaxis or phagocytosis
typically starting with posterior
teeth
Datafrom references 27, 28,44, 45, 69, and 84.
NORMAL FOWATION AND DEVELOPMENT DEFECTS OF HUMAN DENTITION 987
Figure 9. A young woman missing all her posterior teeth. Her father was similarly affected.
Figure 10. This child with X-linked ED has a conical shaped incisor and multiple missing
teeth characteristic of this condition.
NORMAL FORMATION AND DEVELOPMENT DEFECTS OF HUMAN DENTITION 989
ENAMEL DEFECTS
enamel (Fig. 11). Severe fluorosis results in the enamel being markedly
hypomineralized, with a brown color and propensity to break and exces-
sively wear.23
Hereditary enamel defects may occur as a part of a generalized
condition or syndrome or a defect involving only Many heredi-
tary disorders of the ectodermal and combined ectodermal and mesenchy-
ma1 types, such as the trichodento-osseous syndrome (OMIM 1903320),
incontinentia pigmenti, tuberous sclerosis, and junctional epidermolysis
bullosa (OMIM 226700), may have marked enamel involvement.n
Enamel defects associated with syndromic conditions vary substan-
tially, depending on the molecular defect and the role of the genes in
tooth formation. For example, in the trichodento-osseous syndrome, an
autosomal dominant disorder caused by a mutation in the Distal-less 3,
homeobox gene (DLX3), the teeth have enamel hypoplasia that may be
smooth or pitted (Fig. 12) and have taurodontism or elongation of the
pulp chamber.4y,82 Individuals with this condition also have kinky, curly
hair at birth and develop dense or thickened bone.82The DLX3 gene
functions as a transcription factor regulating the expression of other
genes and is important in hair, tooth, and bone formation. Individuals
with junctional forms of eyidermolysis bullosa have varying severities
of generalized enamel hypoplasia and variable expression of skin fragil-
ity and blistering.81The molecular defects that cause junctional epider-
molysis bulosa involve genes that produce proteins essential to main-
taining the integrity between the dermis and epidermis and are
important in normal functioning of the ameloblasts.'
Amelogenesis imperfecta (AI) represents a group of hereditary con-
ditions (Table 2) that manifest enamel defects without evidence of gener-
alized or systemic These conditions are clinically and geneti-
cally diverse. The most widely accepted classification system for A1
considers mode of inheritance and clinical manifestations, with 14 dis-
Figure 11. These incisors with moderate fluorosis have an opaque white appearance and
a round lesion (arrow) in which hypomineralized enamel has been abraded from the surface
during normal function.
NORMAL FORMATION AND DEVELOPMENT DEFECTS OF HUMAN DENTITION 991
Figure 12. The permanent incisors of this adolescent male with the tricho-dento-osseous
syndrome are small and have thin enamel.
DENTIN DEFECTS
Figure 13. This adolescent male shows the brown tooth coloration characteristic of one X-
linked form of amelogenesis imperfecta (pro41thre amelogenin mutation).
tend not to have the severe clinical sequelae that occur with enamel
defects, but dentin malformations that severely affect the form and
function of teeth occur in numerous syndromic and nonsyndromic he-
reditary conditions. The most common Mendelian traits affecting dentin
historically have been classified based on phenotype and histologic
features.59,7x
The dentinogenesis imperfectas (DIs) and dentin dysplasias (DD;
Table 3 ) were classified using clinical, radiographic, and histopathologic
features in 1973, and this nosology remains in use today.59DI has been
classified based on its association with osteogenesis imperfecta (type 1;
OMIM 166240) or not (type 2; OMIM 125490) or with the Brandywine
triracial isolate and large pulp chambers (type 3; OMIM 125500). The
molecular defects in patients with osteogenesis imperfecta include nu-
merous mutations in the pro-alpha chains of collagen type 1 that result
in a phenotype characterized by increased bone fragility.” Although the
dental phenotypes of DI types 1 and 2 seem similar, type 2 is not
associated with any of the nondental phenotypic features of osteogenesis
imperfecta and is not caused by a collagen 1 defect. DI types 2 and 3
are autosomal dominant conditions that have been linked to chromo-
some 4922-21, suggesting that these may be allelic m~tati0ns.l~ Although
the genes responsible for DI types 2 and 3 are unknown, several likely
candidates have been identified, including the dentin matrix acid phospho-
protein gene ( D M P I ) and the dentin sialophosphoprotein gene (DSPP).3,4, 3x
In all three DI types, the teeth have a variable blue-gray to yellow-
brown discoloration that appears opalescent because of the defective,
abnormally colored dentin shining through the translucent enamel (Fig.
Table 3. HERITABLE CONDITIONS OF DENTIN
Condition Clinical Features Radiographic Features Molecular Defect
Dentinogenesis imperfecta Variable blue-gray to yellow-brown Variable pulp obliteration, bulbous Mutations of collagen type 1
type 1 (occurs in some teeth, enamel fracturing, crowns, altered root genes (COLIAI and
forms of osteogenesis excessive wear, primary teeth morphology, increased risk for COLIlA.2)
imperfecta) (OMIM usually more affected than dentigerous cysts
166240) permanent
Dentinogenesis imperfecta Same appearance and variability as Pulp chamber obliteration that can Unknown, linked to 4921
type 2 (OMIM 125490) in DI type 1, often similar begin before tooth eruption, lOCUS
severity in primary and abnormal crown and root
permanent dentitions morphology
Dentinogenesis imperfeda Similar clinical phenotype as DI Large pulp chambers, very thin Unknown, linked to 4921
type 3 (OMIM 125500) types 1 and 2 although typically dentin, bulbous crowns and locus
severe expression with enamel diminished root structure
loss and extensive wear
occurring early
Dentin dysplasia type 1 Normal clinical crown morphology Pulp obliteration and short blunt Unknown, no locus
(OMIM 125400) and coloration in primary and roots in both primary and identified
permanent dentitions, malaligned permanent dentitions
teeth, frequent dental abscess
Dentin dysplasia type 2 Primary dentition has same Pulp obliteration in primary Unknown, linked to 4921
(OMIM 125420) phenotype as DI, permanent dentition, abnormal pulp lotus
dentition has normal to slight morphology and pulp stones in
blue gray discoloration permanent dentition
DI = dentinogenesis imperfecta.
NORMAL FORMATION AND DEVELOPMENT DEFECTS OF HUMAN DENTITION 995
Figure 14. Marked discoloration and severe attrition of the primary dentition are seen in
this child with dentinogenesis imperfecta type II.
996 WRIGHT
Figure 15. The abnormal tooth morphology and complete obliteration of the dental pulp
chambers characteristic of dentinogenesis imperfecta type II.
treatment for the malaligned teeth may increase the longevity of the
dentition.30
DD type 2 (OMIM 125420) is also inherited as an autosomal domi-
nant trait. The primary dentition of DD type 2 seems virtually identical
to that of DI type 2, with yellow-brown to blue-gray discoloration of the
teeth and pulpal obliteration, but in patients with DD type 2, the color
of permanent dentition is normal or only minimally discolored but the
permanent dentition displays abnormal pulpal morphology that may be
shaped like a thistle tube in the anterior teeth.5oPulp stones also are
common in the permanent teeth. Because of the similar phenotype of
the primary teeth, DD type 2 may be an allelic mutation of the gene
responsible for DI type 2. Although the molecular defect for DD type 2
is unknown, it has been linked to the same region as DI type 2 on
chromosome 4921, consistent with it being an allelic mutation.I8 Treat-
ment of DD type 2 in the primary dentition follows the same course as
that used for children with DI.
Many systemic conditions include abnormal dentin formation as a
result of the molecular defect interfering with different dentin develop-
mental pathways. For example, conditions with molecular defects that
influence mineralization, such as hypophosphatasia (i.e., alkaline phos-
phatase defect) and vitamin D-resistant rickets (i.e., vitamin D metabo-
lism defect), can have significant dentin involvement. Many children
with vitamin D-resistant rickets develop dentoalveolar abscesses be-
cause of large pulps with extensive pulp projections (pulp horns) that
become exposed to the oral environment and allow for bacterial invasion
into the tooth.25Other systemic conditions with dentin involvement
include Ehlers-Danlos syndrome, mucopolysaccharidoses, and tumoral
calcinosis.
NORMAL FORMATION AND DEVELOPMENT DEFECTS OF HUMAN DENTITION 997
SUMMARY
Oral health and systemic health are intimately related, and a thor-
ough evaluation of the oral health of children is critical in providing
appropriate health care. By understanding the normal sequence and
patterns of tooth development, clinicians can readily identify children
who deviate from normal dental development and provide appropriate
interventions or make appropriate referrals. Developmental defects of
the human dentition are not uncommon and can severely adversely
affect the physical and psychological health of children. Despite the
severity of some developmental defects of the dentition, the ability to
diagnose and manage these conditions, in most cases, allows children
the benefit of optimal oral health.
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with special reference to the fiber arrangement. Anat Embryo1 (Berl) 188537-549, 1993
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. Address reprint requests to
J. Tim Wright, DDS, MS
Department of Pediatric Dentistry
School of Dentistry CB # 7450
The University of North Carolina
Chapel Hill, NC 27599-7450
e-mail: tim-wright@dentistry.unc.edu