Symposium on Oral Health

The Orofacial Structures and Their

Association with Congenital
Abnormalities

Ray E. Stewart, D.M.D., M.S.*

and Andrew E. Poole, D.D.S., Ph.D.f

This article will discuss the abnormalities of orofacial structures that can
occur in association with various congenital disorders and syndromes. The
importance of the association between orofacial anomalies and other congeni-
tal malformations can be appreciated when one considers that the dysmorphic
development of various tissue and organ systems is often associated with
craniofacial malformation. 23
Certain specific alterations of craniofacial form, structure, or function are
found to be associated with certain syndromes and systemic disturbances to
an extent that they may be classified as cardinal features of those conditions.
Because of this, it is important for the clinician to be cognizant of dys-
morphologic changes of orofacial structures in order to alert him or her to
'I consider certain specific disease entities and to rule out the involvement of
other tissues and organ systems that may be syndromically related.
Dysmorphic changes of craniofacial structures should be discussed using
the same descriptive terminology and nomenclature and the same systems of
classification that have been standardized in the field. In this article, we will
provide a brief review and discussion of (1) the general principles of
dysmorphology; (2) the identification and recognition of craniofacial dys-
morphology; (3) dental abnormalities associated with common congenital
disorders; and (4) orofacial considerations (other than teeth) in the diagnosis
of syndromes.

GENERAL PRINCIPLES OF DYSMORPHOLOGY

There are as many definitions of "a syndrome" as there are syndromolo-

gists, but, in general, any association of two or more abnormalities in the same

*Associate Professor of Pediatrics and Dentistry, Harbor-UCLA Medical Center, Torrance, Cali-
fornia
t Associate Professor of Dentistry, School of Dental Medicine, Department of Pediatric Dentistry,
University of Connecticut Health Center, Farmington, Connecticut

Pediatric Clinics of North America- Vol. 29, No, 3, June 1982

547
548 RAY E. STEWART AND ANDREW E. POOLE

individual can be viewed as a syndrome. The real value of syndrome

identification lies in the description of its natural history, phenotypic expres-
sion, and recurrence risk 6 • With careful delineation of these characteristics,
greater potential exists for the determination of the etiology and pathogenesis
of a syndrome with its prevention or treatment as a long-term view.
Syndromes have been named after individuals, after the systems or
organs affected, after the major symptoms, and more recently by letters of the
alphabet. At a recent meeting of an international committee, however, a first
step toward a standard nomenclature was taken by defining a malformation
and deformation and associated defects as follows: 22
Malformation: a primary structural defect resulting from a localized error
in morphogenesis; for example, cleft palate.
Deformation: an alteration in the shape or structure of a previously
normal part; for example, torticollis.
Malformation sequence: a defect resulting from interuption of a specific
step in development which leads to subsequent abnormalities; for e)(ample,
Robin anomalad.
Malformation syndromes: recognized patterns of malformation presum-
ably having a common etiology but not the result of a single localized error in
morphogenesis; for example, Down's syndrome.
An association: a series of malformations which occur together but do not
currently constitute a syndrome; for example, Wilms' tumor and hemihyper-
trophy.
This classification is not necessarily all-inclusive nor does it always
describe etiology. Many malformations occur alone or as part of a larger
malformation (for example, cleft palate) and may result from a single gene
defect, a combination of genes and environment, or from a pure environmen-
tal insuh. Cohen 6 adds to this list two other categories of syndromes:
dysmetabolic syndromes, which result from a metabolic defect, or dysplastic
syndromes, which result from abnormalities in cell division at the tissue level.
All these levels of abnormality affect the orofacial structures and lead to
nonspecific dysmorphology and to characteristic facies typical of syndromes
resulting from dysmetabolic (cell), dysplastic (tissue), malformation (organ),
and deformation (regional) defects.
Abnormalities of the dentition can include malformations (for example,
peg-shaped teeth), and deformations (for example, dilacerated teeth), but also
should include abnormalities in the number of teeth (missing teeth or
supernumerary teeth), which are probably the result of an error in tooth
induction prior to morphogenesis. Clearly, abnormalities of the dentition can
be commonly associated with generalized defects in calcification (for exam-
ple, pseudohypoparathyroidism), in skin and its appendages (for example,
ectodermal dysplasia), in growth disorders affecting bone matrix synthesis (for
example, osteogenesis imperfecta), and hormone synthesis (for example,
hypopituitarism), and in generalized protein-mucopolysaccharide synthesis
(for example, phenylketonuria and the mucopolysaccharidoses). These syn-
dromes are of the dysmetabolic type. A large category of dental and orofacial
defects fall into a nonspecific category of abnormalities that without knowl-
edge of the nature of the defect, could be part of many syndromes - for
example, enamel hypoplasias or discolored teeth. However, under the as-
 0ROFACIAL STRUCTURES ASSOCIATED WITH CONGENITAL ABNORMALITIES 549
Table 1. Recognizable Abnormalities of the Orofacial Structures
Head (Macrocephaly, Microphaly) Maxilla-Mandible
Aberrant hair pattern Flattened malar region
Malformed cranial vault Large upper jaw
High forehead Micrognathia
Wide fontanelles Prognathic jaw
Mectopic suture Microstomia
Prominent supraorbital ridges Macrostomia
Flattened occiput Downturned mouth

External Ears Oral Cavity

Auricular tags Notched vermillion border
Auricular pits Prominent lips
Abnormal helix Long philtrum
Protuberant ears Lip pits
Low-set ears High arched palate (submucous cleft)
Narrow external auditory meatus Cleft alveolus
Rotated ears Abnormal frenula
Small ears Macroglossia
Abnormal speech (hypernasality)
External Eyes Bifid tongue
Absence of eyelashes (extra eyelashes) Hypertrophied ridges
Epicanthal folds Asymmetric lips
Upward-slanting palpebral fissures
Downward-slanting palpebral fissures Facies
Hypotelorism Flattened
Hypertelorism Coarse
Telecanthus Expressionless
Size and shape of palpebral fissures Broad
Confluent eyebrows Round
Depressed nasal bridge Triangular
Asymmetric
Nose
I Small, upturned nose
Flat nasal bridge
Anteverted nostrils

II Narrow nose
Large, broad nose

I
.I sumption that "the more abnormalities that can be recognized in a given
syndrome, the easier the condition is to diagnose," 6 the recording of those
minor and major anomalies, such as cleft lip or palate, aglossia, anophthalmia,
and so on, (see Table 1) that might be present in the orofacial area is an
important step in delineating a diagnosis and managing the needs of the pa-
tient.

IDENTIFICATION AND RECOGNITION OF CRANIOFACIAL

DYSMORPHOLOGY

The first step in the delineation of a syndrome is similar to that used in

making a diagnosis of any disorder. This involves the taking of an accurate
history, including prenatal and postnatal development, and particularly ob-
taining a good family history. This would be followed by careful physical
550 RAY E. STEWART AND ANDREW E. POOLE

examination of the total body especially observing major and minor defects in
all systems.
The characteristics described in Table 1 represent some of the cardinal
features of craniofacial dysmorphology. Space does not permit a detailed
discussion of all these features, and only those affecting maxilla-mandible and
oral cavity are presented here. The examination of the face and oral cavity can
consist of both qualitative (visual) and quantitative (measurement) observa-
tion. Both are reliable ways of determining craniofacial dysmorphology but
neither method can be the only approach used.
Quantitation of facial form or measurement of the size of the tongue, for
example, is difficult to perform using current methodology, and therefore
subjective clinical assessment is essential, Significant abnormality such as
severe micrognathia is very easy to observe, but a wide variation exists in the
assessment of mild to moderate micrognathia. The latter is often recognized
post hoc aftpr other cardinal features of the syndrome have been delineated.
Another confounding factor in syndrome identification are differences in
expressivity of all the features of the syndrome. This can occur whether the
syndrome is inherited or sporadic, although it is most noticeable in different
members of the same family in inherited syndromes. Only by careful
examination of all members of the family does the transmission from parent to
child become clear. Photographs of distant relatives who are not available for
examination are essential to ensure accuracy of the pedigree. Variation in
penetrance (transmission from generation to generation) and expressivity
(appearance within an individual) are often a characteristic of dominant,in-
heritance.
For this reason, many craniofacial dysmorphologists resort to quantitative
techniques such as direct anthropologic measurement of the face, and
me~surement using x-rays, models, and so on for delineation of abnormali-
ties.
Direct Measurement of the Face
The single most useful predictor of brain development is head circumfer-
ence. With standard charts available from the National Center for Health
Statistics, measurement of head circumference is done in most pediatric
offices and is particularly useful in children and adults with dysmorphic
features. Microcephaly is a particularly poor prognostic indicator for normal
mental development in the ne.wborn and is part of many syndromes affecting
the head and face region. Macrocephaly is also observed in hydrocephaly,
arrhinencephaly, and so on, and is also part of cerebral gigantism (Soto's
syndrome). Accompanying the measurement of head circumference should be
the delineation of the fontanelles, the distance between sutures, the general
shape of the cranial bones, and the amount, distribution and texture of the
hair.
Measurement of the face can be performed using the procedures of
Feingold and Bossert. 9 The distance between the eyes (inner and outer
canthal distance) and the interpupillary distance (hypotelorism and hyper-
telorism) are important observations to be recorded in an examination of the
face, and comparisons should be made to the norms found in standard graphs. 9
Similar measures exist for position, size, and rotation of the ears, breadth of
0ROFACIAL STRUCTURES ASSOCIATED WITH CONGENITAL ABNORMALITIES 551
the nose, nasolabial length, oral opening (intercommissural distance), and lip
thickness. In addition, upper and lower facial height, midface height, and
skull height measures can all be made directly on the face with appropriate
calipers and rulers. Since many of these measures have specific landmarks
from which measurements are made, qualitative assessment of facial sym-
metry is essential to the interpretation of this data.
Indirect Measurement of the Face
X-rays and study casts of the jaws and teeth are often useful in the
interpretation of craniofacial dysmorphology and oral abnormalities.
Cephalometric films of the skull allow measurements of both the bony
and soft tissues of the face to be compared with standard measurements of
normal individuals. These x-rays, both lateral and posteroanterior, are taken
in a standard head-holder that allows for accurate reproduction of the head
from one subject to the next and for rotations of the head in three dimensions
to be minimized. These films are particularly useful in determining whether,
for example, flattening of the malar region in a suspected Treacher-Collins
syndrome is the result of bony or soft tissue abnormalities. Measurement of
the length of the mandible between two well-established landmarks may also
quantitatively determine if micrognathia exists and may subsequently aid in
the prediction of "catch-up." However, these x-rays should be interpreted
with care, since in children with dysmorphology cephalometric x-rays may
not be as easy to standardize and many of the landmarks cannot be as readily
defined.
Study models of the teeth and jaws are especially useful in measurement
of jaw size, palatal vault dimensions, tooth anatomy and occlusion. Dental
x-rays are essential for determining tooth development (calcification), missing
and supernumerary teeth, and crown-root tooth dimension. X-rays are also of
value in recording the general structure and thickness of enamel and dentin
and the size and shape of the pulp cavity. Interpretation of these dental
findings may require the help of a dentist but can be of particular importance
in completely listing all the features of a syndrome.

DENTAL ABNORMALITIES ASSOCIATED WITH

GENERALIZED CONGENITAL DISORDERS

The development of the dentition is but a single factor in the highly

complex phenomenon of craniofacial development. Owing to the unique
pattern of growth and development and the remarkable metabolic stability of
their structure, the teeth provide the clinician with' an opportunity to examine
alterations in form and structure and to extrapolate these observations to
periods of metabolic disruption that occurred during the developmental
history of that tooth. The sequence and regularity of this development subject
the dentition to a wide range of potential disturbances extending over a
remarkably long period of time. The primary teeth contain a permanent
record of metabolic or environmental disturbances that occur during a specific
period of tooth development and incremental growth that begins during the
second trimester of pregnancy. Similarly, the permanent dentition provides
 <:11
<:11
~

Table 2. Normal Chronologie Development of Primary Teeth*

CALCIFICATION CROWN ROOT ROOT TOOTH
INITIATION BEGINS COMPLETED ERUPTION COMPLETED RESORPTION BEGINS SHED
TOOTH (WEEK IN UTERO) (WEEK IN UTERO) (MONTH) (MONTH) (YEAR) (YEAR) (YEAR)

Central incisor 7 14 (13-16) 1-3 6-9 H-2 5-6 7-8

~
Lateral incisor 7 16 (14t-H>!) 2-3 7-10 lt-2 5-6 7-9
Canine 7t 17 (15-18) 9 16-20 2t-3t 6-7 10-12
First molar 8 15t (14t-17) 6 12-16 2 -2t 4-5 9-11 ~
Second molar 10 18! (16-23!) 10-12 20-30 3 4-5 11-12 en
>-l
*From Gorlin, R J, Pindborg, J. ]., and Cohen, M. M., Jr.: Syndromes of the Head and Neck, 2nd. ed. New York, McGraw-Hill Book Co., 1976. Data Sources: t"l

~
Logan, W. H. G., and Kronfeld, R: Development of the human jaws and surrounding structures from birth to the age of 15 years. J. Am. Dent. Assoc., 20:379, 1933;
Schour, I., and Massier, M.: Studies in tooth development. The growth pattern of human teeth. J. Am. Dent. Assoc., 27:1918, 1940; Lunt, R C., and Law, D. B.: A
review of the chronology of calcification of the deciduous teeth. J. Am. Dent. Assoc., 89:599, 1974.

~
~
[;l
::::
tr1
.,
0
0
t"'
t"l
0ROFACIAL STRUCTURES ASSOCIATED WITH CONGENITAL ABNORMALITIES 553
Table 3. Normal Chronologie Development of Secondary Teeth*
CROWN ROOT
INITIATION CALCIFICATION COMPLETED ERUPTION COMPLETED
TOOTH (MONTH) BEGINS (YEAR) (YEAR) (YEAR)

Maxilla
Central incisor 5-5\ in utero 3-4 months 4-5 7-8 10
Lateral incisor 5-5t in utero 1 year 4-5 8-9 11
Canine 5t-6 in utero 4-5 months 6-7 11-12 13-15
First premolar Birth 1!-li years 5-6 10-11 12-13
Second premolar H-8 2-2~ years 6-7 10-12 12-14
First molar 3~-4 in utero Birth 2t-3 6-7 9-10
Second molar 81-9 2t-3 years 7-8 12-13 14-16
Third molar 3t-4 (yr) 7-9 years 12-16 17-25 18-25

Mandible
Central incisor 5-5\ in utero 3-4 months 4-5 6-7 9
Lateral incisor 5-5\ in utero 3-4 months 4-5 7-8 10
Canine 5t-6 in utero 4-5 months 6-7 9-11 12-14
First premolar Birth H-2 years 5-6 10-12 12-13
Second premolar H-8 2\-2~ years 6-7 11-12 13-14
First molar 3!-4 in utero Birth 2t-3 6-7 9-10
Second molar 8t-9 2t-3 years 7-8 11-13 14-15
Third molar 3t-4 (yr) 8-10 years 12-16 17-25 18-25

*From Carlin, R. J., Pindborg, J. J., and Cohen, M. M., Jr.: Syndromes of the Head and Neck.
'2nd. ed. New York, McGraw-Hill Book Co., 1976. Data Sources: Logan, W. H. G., and Kronfeld, R.:
Development of the human jaws and surrounding structures from birth to the age of 15 years,
J. Am. Dent. Assoc., 20:379, 1933; Schour, I., and Massier, M.: Studies in tooth development. The
growth pattern of human teeth. J. Am. Dent. Assoc., 27:1918, 1940. .

an accurate record of disturbances in normal developmental processes for a

period that extends from the time of birth to approximately the twelfth year of
postnatal life. Tables 2 and 3 show the chronologie development of both the
primary and permanent dentition. Familiarity with this sequence of dental
development can be valuable in determining the nature and timing of a
disturbance and can be of particular value in the evaluation of a patient w~th
congenital anomalies.
For descriptive purposes, anatomists have divided the phenomenon of
dental development into several stages: (1) initiation or bud stage; (2)
proliferation or cap stage; (3) histodifferentiation or bell stage; (4) morphodif-
ferentiation; (5) apposition; (6) calcification; and (7) eruption (Fig. 1). Abnor-
malities caused by genetic, environmental, or combinations of these factors
are known to occur at each developmental stage. The anatomy of the tooth and
its supporting structures can be separated into numerous tissues, which
include enamel, dentin, cementum, and the dental pulp, and all of these
tissue types can reflect generalized or specific disturbances in development
throughout the life of a particular tooth. Abnormalities of tissues that can
occur as a result of disruption at each of the developmental stages are
discussed in the context of the syndromes and systemic diseases with which
they are most frequently associated.
554 RAY E. STEWART AND ANDREW E. POOLE

Bud stage
B
Cap stage
c
Bell stage
D
Apposition and
Calcification af bone calcification of
enamel and dentin
y
GROWTH CALCIFICATION

E F G H
\ (Intra-osseous) (Into oral cavity) )
~----~~----~----~y~~,----------------------~.
ERUPTION ATTRITION
Figure L Diagram of life cycle of a human deciduous incisor. The normal resorption of the
root is not indicated. Enamel and bone are drawn in black. (From Bloom, W., and Fawcett, D.: A
Textbook of Histology. lOth ed. Philadelphia, W. B. Saunders Co., 1975. Redrawn and modified
from an original illustration in Schour, 1.: Noyes' Oral Histology and Embryology. 8th ed. Phila-
delphia, Lea and Febiger, 1960.)

Initiation of Tooth Development

A pronounced thickening of the oral ectoderm is the first morphologic
manifestation of tooth development, preceded by an underlying inductive
phenomenon referred to as initiation. There is a growing body of evidence.
that ectomesenchyme derived from the neural crest provides the primary
induction factor in odontogenesis/ 5 Primary odontogenic tissues have dif-
ferentiated and can be identified as the dental lamina in the human embryo as
early as the twenty-eighth day of gestation. The dental lamina appears as an
0ROFACIAL STRUCTURES ASSOCIATED WITH CONGENITAL ABNORMALITIES 555

Figure 2. Photomicrograph of oral ectoderm showing initial invagination signaling initiation

of tooth germ.

epithelial thickening at the lateral margins of the stomodeum at about the

time that the oropharyngeal membrane breaks down.
Proliferation of the dental lamina as projections into the underlying
mesenchyme at specific locations forms the primordia of the primary dental or
enamel organs (Fig. 2). As cells multiply, they increase the size of the dental
organ and begin to undergo differentiation.
Problems during the initiation and proliferation stages are known to
produce anomalies in both number and structure of teeth and are frequently
associated with generalized dysmorphologic features or systemic disturb-
ances.
Abnormalities of Initiation and Proliferation
Congenitally Missing Teeth. Terms to describe the congenital absence
of teeth in the primary or the permanent dentition include hypodontia, the
absence of one or a few teeth; oligodontia, agenesis of numerous teeth
(commonly associated with specific syndromes and/or severe systemic abnor-
malities); and anodontia, an extreme expression of oligodontia indicating the
total absence of teeth. Anodontia has been commonly reported in the most
severe forms of ectodermal dysplasia (see Table 4).
Congenital absence of teeth may arise from: (1) physical obstruction or
disruption of the dental lamina, as seen in the orofaciodigital syndrome, in
which thick bands of hyperplastic connective tissue are attached to the
556 RAY E. STEWART AND ANDREW E. POOLE

Table 4. Syndromes and Systemic Disorders Associated with

Abnormalities of Tooth Number
Hypodontia
Albright hereditary osteodystrophy
. Down syndrome
Ectodermal dysplasia (several varieties)
Ectodermal dysplasia-ectrodactyly-clefting syndrome
Ellis-van Creveld syndrome
Goltz syndrome (focal dermal hypoplasia)
Hallermann-Streiff syndrome
Incontinentia pigmenti syndrome
Johanson-Blizzard syndrome
Miibius-hypoglossia hypodactyly syndrome
Pycnodysostosis
OFD syndrome
Osteogenesis imperfecta
Otopalatodigital syndrome
Rieger syndrome
Trichodento-osseous syndrome
Williams syndrome

Supernumerary Teeth
Cleidocranial dysplasia
Gardner syndrome
Hallermann-Streiff syndrome
OFD syndrome

developing alveolus overlying the dental lamina in the mandibular incisor

area; (2) space limitation, where competition for minimum nutritional re-
quirement in a spatially constricted area can cause tooth germ regression and
agenesis (for example, the third molar); (3) functional abnormalities of the
dental epithelium possibly in some ectodermal dysplasias (Fig. 3); or (4)
failure of induction of the underlying mesenchyme as in neural crest abnor-
malities.8
Supernumerary Teeth (hyperdontia). This phenomenon results from an
overproliferation of cells at various locations along the developing dental
lamina. As with hypodontia, hyperdontia in the primary dentition is rare. It is
seen in approximately 0.5 per cent of children. 14 Supernumerary deciduous
teeth are more prevalent in males and are most frequently located in the
maxillary anterior region. 8
Although hyperdontia has been observed in all tooth-bearing areas of
the permanent dentition, it is seen most frequently (9: 1) in the maxilla. The
trait shows a sex predilection (2: 1) for malesY
Mesiodens is a special type of supernumerary tooth that is usually conical
in shape and is located at or near the midline in the incisal region of the
maxilla. When it erupts, it is normally found either palatal to or between the
central incisors and frequently causes an improper alignment of these teeth.
The sex ratio is 2:1 favoring males. 2
Multiple supernumerary teeth are commonly associated with certain
disorders (for example, cleidocranial dysplasia, an autosomal dominant syn-
drome; and the Gardner syndrome, which is also autosomal dominant) and
0ROFACIAL STRUCTURES ASSOCIATED WITH CONGENITAL ABNORMALITIES 557

Figure 3. Congenital absence of teeth resulting from defective development at initiation and
proliferation stages.

have occasionally been reported in association with the Hallermann-Streiff

and orofaciodigital syndromes. Supernumerary teeth in the maxillary lateral
incisor area are frequently reported in patients with cleft lip and palate. 23
Histodifferentiation and Morphodifferentiation
Histodifferentiation describes the process during tooth development in
which a series of cellular changes results in the formation of four distinct cell
types arranged in layers or zones (Fig. 4: (1) the outer dental epithelium, OE;
(2) the stellate reticulum, SR; (3) the stratum intermedium, Sl; and (4) the
inner enamel epithelium. These layers develop before any enamel or dentin
formation. Various cell types become differentiated in these various zones:
ameloblasts, AM; odontoblasts, OB. Other cell types will differentiate later in
development and include cementoblasts and differentiated pulp compo-
nents.
Morphodifferentiation is the process whereby the tooth germ assumes the
form of the developing crown- that is, an incisor, canine, pre-molar, or molar
(Fig. 5). The process begins along the periphery of the dental organ, where
the ameloblasts are displaced outwardly, beginning at the tip of the tooth, and
lay down the enamel matrix in an incremental fashion as they retreat (Fig. 6).
The cell layer continues to move outward until the full enamel cap of the
crown is formed in the shape of the developing tooth. A simultaneous process
occurs on the inside of the dental organ where a unicellular layer of
mesodermal cells, the odontoblasts, develop opposite the ameloblasts. These
cells are displaced inward, laying down dentin in an incremental pattern,
 558 RAY E. STEWART AND ANDREW E. POOLE

Figure 4. HiHistodifferentiation;
todiff r ntiation ; th thetooth
toothg germ
rm con ·i ·t ofof several
consists ral c cell
II type
typesat atthithis tag .
stage.
Ameloblasts
m lobla t ( (AM), odontoblasts
i ), odontobla. (OB),
t (OB), andandariou
various
' tistissue
u prprecursors such
cur ors ' uch a as
d dental pulp
ntal pulp (P),t stellate
(P), lIat
reticulum
r ticulum (SR)
( R) andand outouter
r nam I pith
enamel epithelium
lium ( (OE)
E ) ar are
di distinguishable.
tingui habl .

Figur
Figure5. 5. During
Duringmorphodif~ r ntiation th the
morphodifferentiation tooth
toothgerm
germa assumes
um th thehap ofof
shape th the
crown ofof
crown th the
tooth that
tooth \i ill
that d develop.
will lop . In In
thithis
cascase,
, onone
r cogniz . th the
recognizes g germ
rm a!> asada developing
loping in incisor.
i or.
0ROFACIAL STRUCTURES ASSOCIATED WITH CONGENITAL ABNORMALITIES 559

Figure 6. During apposition and calcification, the ameloblasts (AM) and odontoblasts (Ob)
begin to lay down enamel matrix (EM) and dentinal matrix (DM), which begin to calcify soon after
formation.

again beginning at the tooth tip. The process continues inward and downward
to form the bulk of the crown and root of the tooth, enclosing the mesodermal
tissue in the center to form the structure that ultimately becomes the dental
pulp.

Abnormalities of Histodifferentiation and Morphodifferentiation

Abnormalities, resulting in a variety of clinical entities, can occur at
either of these stages and are due to either genetic or environmental factors or
a combination of both.
Melnick and Shields 16 have proposed a model for the classification of the
various forms of structural anomalies, which they call "odontodysmorphogen-
esis." This model is based on the fact that the developmental steps leading to
the formation of any organ, including teeth, involve a sequence of events that
can generally be thought of as induction of cell groups, cellular migration,
cellular interaction with a new "environment," and differentiation into
specific tissue types.
This model provides a coherent and unified classification of the various
forms of odontodysmorphogenesis. The model includes two major causes,
mutational dysmorphogenesis and environmental dysmorphogenesis. The
first would be mutant somatic mesodermal organizer genes leading to aber-
rant cell surface proteins and thus to abnormal migration; the second subclas-
sification would be mutant interpretational genes leading to an abnormal oral
mesodermal type and thus to incorrect induction of the oral epithelium.
Environmental dysmorphogenesis would include malformations such as
fusion and dilaceration.
Table 5 outlines various dental abnormalities that can be attributed to
various categories of odontodysmorphogenesis.
560 RAY E. STEWART AND ANDREW E. POOLE

Table 5. Forms of Structural Abnormalities of

Histodifferentiation and Morphodifferentiation
Mutational Dysmorphogenesis
Mutant mesodermal organizer genes
Anodontia
Supernumerary teeth
Predeciduous teeth
Multiple odontomas
Odontodysplasia
Mutant mesodermal interpretational genes
Anodontia, partial or complete
Absence of single tooth or pair of homologous teeth
Peg-shaped lateral incisors
Microdontia
Macrodontia
Schizodontism (gemination)
Dens invaginatus
Dens evaginatus
Single odontomas
Environmental Dysmorphogenesis
Syndontism (fusion)
Dilaceration

Apposition
Apposition describes the phase during the development of the tooth
when the ameloblasts and odontoblasts begin to secrete and deposit enamel
and dentin proteins respectively. During periods prior to matrix formation,
the ameloblasts exert an influence on adjacent mesenchyme to differentiate a
layer of cells that will become preodontoblasts (the precursors of dentin-
forming cells). The ultimate shape of the dentoenameljunction is determined
at this time. Enamel matrix is initially deposited at the occlusal or incisal
surface of the developing tooth and is followed almost immediately by
deposition of dentin matrix (See Fig. 6).

CALCIFICATION

The process of calcification of enamel and dentin occurs beginning with

the matrix material, which is formed first (at the dentoenamel junction) and
progresses outwardly in the case of enamel and inwardly in the case of dentin.
The specific details of how each of these tissues undergoes calcification and
the abnormalities that can .arise in each will be discussed separately.

ABNORMALITIES OF ENAMEL FORMATION

Enamel hypoplasia is the incomplete or defective formation of dental

enamel. It may involve only the primary dentition, only the permanent
dentition, or both, and presents extensive variability in its clinical appear-
ance. Mild hypoplasia may be manifested by a few small grooves, pits, or
0ROFACIAL STRUCTURES ASSOCIATED WITH CONGENITAL ABNORMALITIES 561
fissures on the enamel surface. In more severe conditions, the enamel may
exhibit rows of deep pits or grooves horizontally across the tooth surface. In
the most severe cases, there is absence of enamel, suggesting a prolonged
disturbance of the ameloblasts.
Enamel formation occurs in two stages: deposition of enamel matrix and
calcification of the matrix during the maturation stage. Enamel hypoplasia
occurs as a result of disturbance in the formation of enamel matrix, resulting in
a deficient amount of matrix, which may calcify normally. Conversely, a
normal amount of matrix may be formed that does not calcify properly. Yet
another possibility is that the matrix is formed in normal amounts and calcifies
properly, but after eruption, calcification is altered owing to exposure to
substances that remove calcium ions from the apatite structure.
A number of factors can adversely affect the ameloblasts and produce
hypoplasia: (1) nutritional deficiency (vitamins A, C, and D); (2) exanthema-
tous disease (measles, chickenpox, scarlet fever); (3) congenital syphilis; (4)
birth related injuries such as prematurity, Rh hemolytic disease; (5) local
infection or trauma: (6) ingestion of chemicals (fluoride, tetracycline); and (7)
genetic causes (amelogenesis imperfecta). 24
As indicated earlier, the crowns of developing teeth, by the very nature of
their developmental history, provide a permanent record of any metabolic or
systemic disturbances that occur during the course of the tooth's formation. By
correlating the position of the hypoplasia clinically with the chronology of
development (Tables 2 and 3), the clinician can estimate the timing of the
systemic events leading to this hypoplasia (Fig. 7A and B).
Nutritional Deficiency
The most commonly repmted form of enamel hypoplasia occurs in
children subjected to chronic vitamin deficiency, particularly of vitamin D.
This phenomenon was especially prevalent before vitamin D supplementa-
tion of milk supplies. Insufficient quantities of vitamin D cause rickets with
characteristic bowing of weight-bearing bones and development of rachitic
rosary at the costochondral junction. These deformities may become perma-
nent if the dietary deficiencies are not corrected early.
Of children sufferi.ng from rickets, approximately 50 per cent will also
show signs of enamel hypoplasia. This hypoplasia occurs most commonly as a
pitting that appears in horizontal rows on the tooth and corresponds to the
matrix formed at the time of the dietary deficiency. The extent of the pitting is
directly proportional to the duration of the deficiency; the longer the time, the
greater the area of hypoplasia. The pitting characteristically picks VP stains
and discolorations that are extrinsic and not incorporated into the enamel
matrix itself. Although vitamin D deficiency is most widely associated with
enamel hypoplasia, deficiencies of vitamins A and C have also been implicat-
ed.
Exanthematous Disease
Many of the so-called "diseases of childhood" are accompanied by a
temporary elevation in body temperature that may remain elevated for
prolonged periods (several weeks), and under these circumstances the ame-
loblasts are adversely affected. 24 The result can be an enamel hypoplasia that
562 RAY E. STEWART AND ANDREW E. POOLE

Figure 7. A, Hypocalcification of primary teeth. B, Hypocalcification of permanent teeth. Note

distinct lines of involvement indicating specific times in development when the hypoplasia oc-
curred.
0ROFACIAL STRUCTURES ASSOCIATED WITH CONGENITAL ABNORMALITIES 563
is clinically identical to the pitted hypoplasias seen in nutritional deficien-
cies.
Congenital Syphilis
The teratogenic effects of microorganisms on developing teeth has not
been substantiated in many instances, but because of the susceptibility of
ameloblasts to environmental insults it would not be surprising if enamel
defects occurred in fetuses exposed to prenatal infection during critical stages
of tooth development.
The enamel defect caused by exposure to Treponema pallidum is
characterized by a generalized hypoplasia that significantly alters crown
formation and size. The most dramatically affected teeth are the permanent
incisors and first molars. Affected incisors are characteristically "screwdriver"
shaped, with tapering marginal ridges convering toward the incisal edge,
which is frequently notched. Such teeth are referred to as "Hutchinson
incisors." The crowns of first permanent molars involved in congenital
syphilis often have irregular occlusal surfaces with multiple enamel pearls or
globules and are referred to as "mulberry molars."
Another microorganism that has been associated with enamel defects is
the rubella virus. Children born to mothers who contracted rubella during the
first trimester of pregnancy often show generalized enamel hypoplasia in
conjunction with the other neurologic and anatomic defects associated with
this syndrome.
Local Trauma or Infection
Localized enamel hypoplasia, involving a single or very few teeth, often
results from damage to a developing tooth bud due to trauma or infection from
a primary predecessor. The extent and nature of the hypoplasia can vary from
mild, in which there is a slight brown discoloration of the enamel, to severe,
in which pitting and irregularity may extend over the whole crown. The
severity of the defect depends on the stage of development of the permanent
tooth and on the magnitude of the insult from the primary predecessor. This
type of defect is termed Turner hypoplasia.
Hypoplasia Due to Fluoride Ingestion
Endemic fluorosis is a disturbance of dental development related to
excessive ingestion of fluoride during critical stages of dental development.
In its mildest form, it affects the ameloblasts during the appositional stage of
enamel formation. However, there is no histologic evidence that actual cell
damage, in more severe forms, causes the production of defective or deficient
organic matrix. At extremely high levels there may be interference with the
calcification process. The fluorosis is characterized by a lusterless, opaque
appearance to the enamel, which is white in the mild forms and yellow to
brown in the more severe forms (Fig. 8). In its most severe form, fluorosis can
grossly alter the morphology of the crown. It occurs symmetrically in the
dental arches but sometimes with significant variability in the degree ofhypo-
plasia.18
Ingestion of Hypoplasia Caused by Tetracycline
Observations as early as 1956 noted the association between ingestion of
tetracycline and intrinsic staining of dental enamel. Tetracycline is incor-
564 RAY E. STEWART AND ANDREW E. POOLE

Figure 8. Hypoplasia due to excessive fluoride ingestion.

porated into calcifying enamel matrix by the formation of a tetracycline-

calcium orthophosphate complex. Incorporation of tetracycline during min-
eralization produces this complex, which on eruption of the teeth and
exposure to ultraviolet light (sunlight) causes discoloration ranging from light
yellow to brown and varying degrees ofhypocalcification. To prevent this, the
clinician should avoid, when possible, prescribing tetracyclines during preg-
nancy and postnatally until the child reaches eight years of age, when most
teeth have completed calcification. The dose, time of administration, and
type of drug all influence the nature and extent of the discoloration. This is a
very disfiguring dental defect that can be avoided and has recently become
important medicolegally. 18
Amelogenesis Imperfecta
Amelogenesis imperfecta is a relatively rare developmental disturbance
of the dentition that occurs either as a result of abnormal function of the
enamel-forming cells (the ameloblasts) or in the structural deposition and
calcification of the enamel matrix secreted by the ameloblasts.
The classification of the various types of amelogenesis imperfecta is
based on the clinical appearance of the defect, the stage in enamel develop-
ment in which the abnormality occurs, and the pattern of genetic transmission
in families. 26
Table 6 provides a summary of the currently recognized forms of
amelogenesis imperfecta and the various features that characterize each type.
Figures 9 thru 15 demonstrate the clinical features of many of these disturb-
ances.

ABNORMALITIES OF DENTINOGENESIS
Dentin matrix is formed by odontoblasts that arise as specialized cells
from the dental papilla shortly after ameloblast formation. The first signs of
0ROFACIAL STRUCTURES ASSOCIATED WITH CONGENITAL ABNORMALITIES 565
dental papilla formation occur at the bud stage of tooth development as a
condensation on its inferior surface. The formation of the ameloblast layer
from the inner enamel epithelium induces differentiation of the odontoblasts.
These odontoblasts produce collagen fibril bundles that make up the matrix
for the first dentin, or predentin. Soon after the matrix is laid down, the
calcification begins with seeding of apatite crystals throughout the matrix.
These start out as tiny spherules that grow and eventually fuse with their
neighbors until a uniform calcifying front is formed. All components of the
matrix become mineralized except the cell processes, which become trapped
in dentin tubules.
Abnormalities of dentin formation will be considered in two large groups:
(1) those that are primary diseases of dentin itself and (2) those in which the
dentin defect accompanies defects in other tissue types or organ systems. The
latter category, of secondary dentin defects, contains syndromes in which
there is an obvious relationship between the dentin and other affected tissues
(for example, vitamin D-resistant rickets) and syndromes with no apparent
relationship among the affected tissues (Ehlers-Danlos syndrome).
Primary Diseases
Primary dentin defects can be classified into two basic groups, the
dentinogenesis imperfectas and the dentin dysplasias. Within each group,
types are identified by Roman numerals (with type I the least severe and type
II the most severe. Table 7 lists the specific findings for each type as a means
of differentiation. 21
Secondary Diseases
Dental Manifestations of Familial Hypophosphatemic Rickets or
VDRR. The clinical, radiographic, and histopathologic dental features of
vitamin D-resistant rickets are sufficiently characteristic to require a separate
discussion. The dental problems may be the first overt signs of this syndrome;
thus the knowledgeable dentist may be the first person to bring it to the
attention of the physician.
The clinical evidence of this problem is the spontaneous appearance of
abscesses and fistulae in teeth that have no other obvious pathology. The
problem affects both primary and permanent teeth and radiographically
exhibits enlarged pulp chambers often with the extension of the pulp horns
into the cusp tips. Vitamin D-resistant rickets rarely affects enamel, its. effects
being largely confined to dentin. In contrast, one of the routine clinical
findings with vitamin D-dependent rickets is a severe hypoplasia of the
incisal and occlusal enamel, with radiographs showing dentin changes ex-
emplified by large pulp chambers and delayed closure of root apices.
Hereditary Osteodystrophy of Albright. Albright hereditary osteodys-
trophy is a symptom complex whose primary feature is a failure of end-organ
responsiveness to parathyroid hormone (PTH). Chemically, the disease is
characterized by hypocalcemia and hyperphosphatemia, just as in hypo-
parathyroidism.
There are defects of all the primary dental structures: (1) enamel
hypoplasia manifested as a dull-white appearance with pitting of the surface;
(2) small crowns and short roots with blunted apices; (3) large pulp chambers;
(4) unusual histopathologic changes in the dentin; and (5) cementum that is
Text continues on page 572
 ~
Q')
Q')

Table 6. Varieties of Amelogenesis lmperfefta"

ALL TEETH PRIMARY PERMANENT
AFFECTED DENTITION DENTITION
CLINICAL FEATURES INHERITANCE EQUALLY AFFECTED AFFECTED

HYPOPLASTIC TYPES
Local hypoplastic type Varies from horizontal rows of pits or linear Autosomal dominant ± + ±
depressions to large areas of hypoplastic
depressions
Smooth hypoplastic type Enamel is thin, hard, glossy, with smooth Autosomal dominant + + + ::0
:>
(Fig. 8) surface. Color varies from white to brown. ~

Spacing between teeth. t:"l

Rough hypoplastic type Enamel is hard, with rough granular surface. Autosomal dominant Vl
>-l
(Fig. 9) Enamel is deficient in amount, white to t<j

yellow-white in color. ~
~
Rough hypoplastic type Nearly complete absence of enamel. Autosomal recessive + + + >-l
(enamel agenesis) Yellow color. Surface is rough and :>
(Fig. 10) granular. Teeth appear widely spaced.
zt)
Numerous missing teeth and impactions.
Pitted hypoplastic type
~
t)
Enamel 'is hard, normal thickness with Autosomal dominant + ± +
(Fig. 11) numerous pinhole pits on all surfaces. ~
Pits become stained brown or black. :;::
Smooth hypoplastic type Appearance different in males and females. X-linked dominant males + + t:"l
Males: smooth, shiny, thin, yellow-brown. + "d
0
Females: lines of alternating normal and females 0
t"'
hypoplastic enamel. t<j
HYPOMATURATION TYPES 0
Hypomaturation-hypoplastic type Associated with taurodontism, possibly same Autosomal dominant ~
as trichodento-osseous syndrome
~
+ +
~
Sex linked hypomaturation type Males: enamel normal thickness, soft, X-linked recessive males
(Fig. 12) mottled yellow-white color, chips easily + CJl
females >-l
Pigmented hypomaturation type Enamel colored milky. Brown, become Autosomal recessive + + + ~
n
(Fig. 13) darkly stained after eruption. Normal >-l
thickness but chips easily
c:
~
HYPOCALCIFIED TYPES
"'
>
Common hypocalcified type Most common form of amelogenesis Autosomal dominant + + + "'"'0
(Fig. 14) imperfecta. Enamel normal thickness, n
very soft and cheesy, many impactions. ;;:
>-l
Yellow to brown color. Enamel rapidly worn t'l
0
away. Anterior open bite, extensive
:18
calculus accumulation.
Recessive hypocalcified type Same as common variety but more severe. Autosomal recessive + + + ~
ll
0
•Modified from Witkop, C.}.: Heritable defects of enamel. In Stewart, R. E., and Prescott, G. H. (eds.): Oral Facial Genetics. St. Louis, C. V. Mosby Co., z
1976. C'l
t'l
z
~
>
c;
z
0

~
t"
a
t'l
"'

I:Jl
~
.....
568 RAY E. STEWART AND ANDREW E. POOLE

Figure
Figur9. 9. Amelogenesis
Am log n 'isimperfecta, smooth
imp r£ eta, moothhypoplastic typepinherited
hypopla tiet inh rit as autosomal
dasauto omaldominant.
dominant.

Figure
Figur 10.1 . Amelogenesis
Am log n imperfecta,
imp rfeeta,rough
roughhypoplastic
h p pIa tietype.
t p Autosomal
. Auto omaldominant
dominantinheri-
inheri-
tance.
tane .
 0ROFACIAL STRUCTURES ASSOCIATED WITH CONGENITAL ABNORMALITIES 569

Figure11.11. Am
Figur Amelogenesis
Jog n imperfecta,
imp roughhypopJa
r~ eta, rough hypoplastic type.
tie typ Autosomal
. Auto omaJ r recessive
e inherit-
e inh rit-
ance.
ane .

Figure12.12. m
Figur Amelogenesis
Jog n imp rt ta, pitt
imperfecta, pitted
d h hypoplastic
popJa tie typtype. Autosomal
. Auto dominant
omaJ domin nt inhinherit-
rit-
anance.
570 RAY E. STEWART AND ANDREW E. POOLE

Figur
Figure 13.
13. m log n i. imp
Amelogenesis rt eta, hhypomaturation
imperfecta, pomaturation ttype.
p . X-linked
-link d inh rit, ne .
inheritance.

Figur 14.
Figure m log n
14. Amelogenesis imp r~ ta, pigmented
imperfecta, pigm nt d hypomaturation
hypomaturation type.
t p . Autosomal
Auto omal recessive
r
inh ritane
inheritance.
 Figure 15. Amelogenesis imperfecta, common hypocalcified type. Autosomal dominant in-
heritance.

Table 7. Diagnostic Features of Types I, II, and III

Dentinogenesis I mperfecta and Types I and II Dentin Dysplasia* f
DI-I m-rr DI-III DD-I DD-II

Clinical Features
Primary teeth amber, translucent + ++ + + ++
Secondary teeth discolored + ++ ++
Discoloration in both dentitions + ++ ++
Loose teeth + + ++
Rapid attrition of crowns + ++ ++
Fragile roots + + + +
Radiographic Features
Ovoid crowns ++ ++ ++
Short tapering roots + + + ++
Obliteration of pulp cavities
Before eruption + + + ++
After eruption + ++ + +
Horizontal line at DEJ
(crescent-shaped pulp chamber) ++
Apical extension of pulp chamber
Multiple apical radiolucencies + + + ++
Thistle-tube shape to pulp chamber +
Reduced x-ray contrast of dentin ++ ++ + ++
Pulp stones iu pulp chamber ++
Histopathologic Features
True denticles + + + ++ ++
False denticles + + + +
Features in Common
Primary teeth more severely affected ++ ++ ++ ++ ++
Normal mantle dentin ++ ++ ++ ++ ++
Abnormal radicular dentin ++ ++ ++ + ++
Normal enamel + + + ++ ++
Interglobular dentin + ++ + + ++
Scalloping of DEJ + + + ++ ++

*From Bixler, D., In Stewart, R. E., and Prescott, G. H. (eds.): Oral Facial Genetics, St. Louis,
The C. V. Mosby Co., 1976.
fKey: ++,typically evident in all teeth; +,variable in frequency or severity; -absent.

571
 572 RAY E. STEWART AND ANDREW E. POOLE

thick and of the cellular type with a cartilage-like appearance. The enlarged
pulp chambers in this condition are mostly filled with calcified material that
shows a whorled pattern. In reviewing these findings, Ritchie 19 noted that
they are similar to the dental changes observed in idiopathic hypoparathyroi-
dism. Thus, the dental alterations are representative of the overall metabolic
picture, which favors generalized ectopic calcification and other mineraliza-
tion defects and is therefore not a primary dental disease in itself. .
Dentin Defects, in Other Syndromes. Dental changes nearly identical to
those observed in type I dentin dysplasia have been observed in patients with
generalized calcinosis and in the Ehlers-Danlos syndrome. The significance
of these observations is presently unknown, but they are included in this
discussion because of their possible relationship to a heritable primary
disease of dentin.
Ehlers-Danlos syndrome is a disease complex presently consisting of at
least eight different heritable entities. In each case, a specific defect of
collagen is probable although such specificity has been identified only for a
few of the different types. Nevertheless, reports indicate that dentin and
cementum abnormalities exist in the teeth of persons affected with certain
types of Ehlers-Danlos syndrome.
Calcinosis is abnormal deposition of calcium within tissues, and two
broad categories can be recognized: calcinosis universalis and calcinosis
circumscripta. A third rare form, tumoral calcinosis, has also been described.
In it, calcific deposits are typically periarticular, dense, irregular, and occur in
subcutaneous tissue. Tooth roots have gross pulp stones in the coronal third
that obliterate the pulp and even expand the root area. This is a developmen-
tal abnormality believed to be due to calcification of the dental papilla.
Abnormalities in Eruption
There is a broad range of variation in normal eruption times of the
deciduous and permanent teeth. Because of this inherent biologic variation, it
is difficult to determine when the eruption dates for a given person are
outside normal limits. Nevertheless, certain eruption times are grossly
beyond the extremes of normal and may be considered pathologic, although
the significance of this is frequently not apparent.
The normal eruption sequence of the dentition is similar in all popula-
tions (Tables 2 and 3). The central incisors are the first teeth to erupt in
children- followed by the lateral incisors, first molars, canines, and second
molars, in that order. Various factors have been implicated in the control of
eruption: genetic, environmental, and systemic.
Socioeconomic levels, which affect nutrition and personal hygiene, 8 have
also been linked to retarded eruption of anterior teeth and accelerated
emergence of posterior teeth.
Low birth weight, but not birth order, has been associated with delayed
emergence of permanent teeth. Conversely, early eruption has been associat-
ed with increased birth weight. In monozygotic twins, the child with the
higher recorded birth weight also has the earlier eruption time. 18
Although nutrition has been implicated as a factor in dental development,
teeth are at a substantially lower risk than are skeletal and other somatic
structures for detrimental environmental influences. In one study, nutrition
0ROFACIAL STRUCTURES ASSOCIATED WITH CONGENITAL ABNORMALITIES 573
Table 8. Syndromes and Systemic Disorders Associated with
Anomalies of Eruption
Neonatal Teeth Premature Eruption
Ellis-van Creveld syndrome Precocious puberty
Hallermann-Streiff syndrome Hyperthyroidism
Pachyonychia congenita syndrome Hemifacial hypertrophy
Sturge-Weber syndrome
Delayed Eruption
Albright hereditary osteodystrophy Premature Loss
Cleidocranial dysplasia Acrodynia
Down syndrome Hajdu-Cheney syndrome
Dubowitz syndrome (aero-osteolysis syndrome)
Hypothyroidism Hypophosphatasia syndrome
Hypopituitarism Hand-Schiiller-Christian syndrome
Hemifacial atrophy Werner syndrome
Ellis-van Creveld syndrome Papillon-Lefevre syndrome
Gardner syndrome Juvenile periodontosis (Gottlieb syndrome)
Goltz syndrome Ehlers-Danlos syndrome Type VIII
Mucopolysaccharidosis
lncontinentia pigmenti syndrome
Osteogenesis imperfecta
Progeria

was shown to correlate only slightly with dental development, accounting for
less than 1 per cent of the variability. 11
Delayed eruption may be due to systemic disorders and has been
associated with several syndromes (Table 8). Delayed permanent tooth
eruption is associated with the Down syndrome, Turner syndrome, cleido-
cranial dysplasia, and hemifacial atrophy. 23
Precocious eruption is rare compared with retarded eruption but is seen
in cases of precocious puberty, hyperthyroidism, and hemifacial hypertrophy
as well as in affected areas of the dental arch in Sturge-Weber syndrome. 23
If deciduous teeth emerge before the first three months of life, they are
classified as premature or predeciduous. Those that are present at .birth are
called natal teeth; those that erupt during the neonatal period, from birth to
30 days, are designated neonatal teeth (Figs. 16 and 17). Of the total, 90 per
cent are premature primary teeth (85 per cent of which are mandibular
incisors) and 10 per cent are supernumerary calcified structures or prede-
ciduous teeth. There is no apparent sex predilection. Natal teeth appear more
frequently than neonatal teeth (3: 1) although they are an expression· of the
same characteristic. Familial occurrences have been reported frequently.
Hereditary transmission has been most characteristic of an autosomal domi-
nant trait. 1
Natal and neonatal teeth are reportedly associated with three syndromes:
chondroectodermal dysplasia or Ellis-van Creveld syndrome (autosomal
recessive), Hallermann-Streiff syndrome (autosomal dominant), and pa-
chyonychia congenita (autosomal dominant). 23
Premature Loss of Teeth
Premature loss of teeth is commonly caused by dental caries or periodon-
tal disease and their complications. Premature development of the succedan-
574 RAY E. STEWART AND ANDREW E. POOLE

Figure 16. Radiograph of patient with cleidocranial dysplasia demonstrating large number of
unerupted permanent teeth. Patient wore dentures for 13 years prior to this radiograph.

eous permanent teeth may also give rise to early shedding. Premature loss of
primary teeth may be seen in acrodynia, Hand-Schiiller-Christian disease,
neonatal maxillitis, hypophosphatasia, and Papillon-Lefevre syndrome. Pre-
mature loss of permanent teeth is seen in various chronic metabolic dis-
eases.24

ORO-FACIAL CONSIDERATIONS IN THE DIAGNOSIS OF

SYNDROMES

Only those characteristics (other than teeth) specifically related to the oral
cavity and its associated areas of the face will be discussed here. The most
common general syndromes affecting these structures are listed in Table 9.

Figure 17. Natal tooth in newborn.

0ROFACIAL STRUCTURES ASSOCIATED WITH CONGENITAL ABNORMALITIES 575

Table 9. Orofacial Considerations in the Diagnosis

of Craniofacial Syndromes
ORGAN FEATURE SYNDROME INHERITANCE

Tongue Macroglossia Beckwith-Wiedemann Sporadic

Microglossia-aglossia Aglossia-adactylia Sporadic
Mobius Sporadic
M ultilobulated OFD I Dominant, X-linked
or autosomal
Bifid OFD II A.R.
Hypermobility Ehlers-Danlos Various
Palate Cleft lip and palate Isolated Multifactorial
Associated with several
syndromes, including:
EECsyndrome,OFDiandll, A.D. (see above)
Trisomy 18, Chromosomal
VanderWoude, etc. A.D.
High-Arched A pert A.D.
Cleidocranial dysplasia A.D.
Crouzon, etc. A.D.
Isolated cleft palate A pert A.D.
(bifid uvula) Robin Sporadic
Stickler A.D.
OFDI (see above)
Treacher-Collins, etc. A.D.
Soft tissue Frenulae OFD I and II (see above)
of mouth Ellis-van Creveld A.R.
Gingivae Ehlers-Danlos
Papillon Lefevre A.R.
Cowder A.D.
Mandible Micrognathia First arch Various
Hypoglossia-hypodactylia Sporadic
Robin Sporadic
Fetal methadone Sporadic
Hallermann-Streiff A.D.
Chromosomal (13, 18 trisomies)
Asymmetric Facioauriculovertebral Sporadic
Klippel-Trenaunay-Weber Sporadic
Prognathism Acrodysostosis Sporadic
Maxilla Hypoplasia Maxillonasal dysplasia ? Sporadic
Stickler A.D.
Crouzon A.D.
18q-
de Lange Sporadic
Oral Opening Microstomia Otopalatodigital X-linked dominant
Robinow A.D.
Hallermann-Streiff A.D.-Sporadic
Macrostomia Facioauriculovertebral Sporadic
Mucopolysaccharidoses Various
18q-
576 RAY E. STEWART AND ANDREW E. POOLE

Figure 18. Large tongue (mac-

roglossia) in Beckwith-Wiedemann
syndrome.

This list is not intended to be all-inclusive and, for the most part, includes
only those syndromes in which abnormal orofacial structures are an important
part of the diagnosis.
The tongue can be altered either in size, shape, or mobility. Macroglossia
is a relative term referring to an actual increase in the volume of the tongue
in the oral cavity. In Beckwith-Wiedemann syndrome (exophthalmos-mac-
roglossia-gigantism- Fig. 18), the tongue is very large, often protrudes
from the mouth, and can be extended a considerable distance without
narrowing. Persistence of this tongue size can cause significant feeding
problems and, usually later, divergence and protrusion of the lower teeth.
Increase in tongue size can also be associated with a sh01t neck and anterior
placement of the hyoid bone (as in Down syndrome). In Down syndrome,
surgical correction is not usually indicated but is often necessary in Beckwith-
Wiedemann syndrome. Microglossia (hypoglossia) or aglossia (Fig. 19) is
seen in aglossia-adactylia syndrome usually in association with hypoplastic
alveolar ridges, micrognathia, and limb reduction deformities. Babies with
this syndrome often have some feeding problems in the newborn period. A
small tongue is also a feature of congenital facial diplegia (Mobius syn-
drome).
Change in the shape of the tongue can be the result of hemihypertrophy
(as in Klippel-Trenaunay-Weber syndrome) and is occasionally the result of a
hemangioma or cystic hygroma in the body of the tongue. Hemihypertrophy
0ROFACIAL STRUCTURES ASSOCIATED WITH CONGENITAL ABNORMALITIES 577

Figure 19. Microglossia in hypoglossia-hypodactylia syndrome.

can also result from unilateral involvement of the twelfth cranial nerve with
resultant deviation of the tongue to the affected side on protrusion. With time,
asymmetric tongue development can result in asymmetric development of the
jaws.
A multilobulated tongue is common in orofacial digital (OFD) syndrome
I and II. OFD type I is seen only in females, in whom the tongue is often
multilobulated and associated with abnormal frenula extending from the
cheeks and lips over the alveolar ridges (Fig. 20). It consists additionally of
characteristic facies, asymmetrical limb reduction deformities with clin-
odactyly and cleft palate. These children need early careful observation for

Figure 20. Irregular clefts in alveolar ridge, palate, and tongue in OFD syndrome.
578 RAY E. STEWART AND ANDREW E. POOLE

Figure 21. Hypertrophic lingual frenum. Frequently referred to as ankyloglossia.

more generalized defects (such as renal) and many die in infancy. OFD II
(Mohr syndrome) is generally less severe and the tongue is more frequently
bifid; hyperplastic frenula do occur and conductive deafness is frequently as-
sociated.
Change in the mobility of the tongue can be the result of a short, or
thickened lingual frenum (Fig. 21) and can be part of OFD I and II or the
Ellis-van Creveld syndrome. Hypermobility of the tongue is common in the
various types of Ehlers-Danlos syndrome in which hyperextensibility of the
tongue is common. Benign forms of this syndrome are often not recognized
until the teenage years. The ability to extend the tongue to the tip of the nose
is a frequent sign.
The palate can be cleft or high arched with or without the presence of a
submucous cleft. Cleft palate can be found alone or in conjunction with cleft
lip. Most data suggest that isolated cleft palate represents a genetically
separate defect from cleft lip and cleft palate. 10 A few of the syndromes
associated with clefts are found in Table 9. Cohen 6 lists at least 30 such
syndromes, and many more undoubtedly exist. In examining 154 syndromes
involving cleft lip and cleft palate, Cohen reported that over 50 per cent were
single gene defects (autosomal dominant, recessive, and sex-linked), 20 per
cent were chromosomal defects, 4 per cent were due to environmental
teratogens, and over 25 per cent were of unknown etiology. 7 The Robin
anomaly, a special V or U -shaped cleft of the palate associated with signific~nt
micrognathia and often with respiratory and feeding problems in the new-
born, is a defect often seen alone or following the use of environmental
teratogens such as alcohol, methadone, or hydantoin early in pregnancy (tenth
to twelfth weeks). It can occur in conjunction with a specific syndrome, such
as Stickler syndrome, and is often associated with growth delay. A complete
discussion of clefts is beyond the scope of this article, but of particular note is
the van der Woude syndrome, an autosomal dominant condition in which
0ROFACIAL STRUCTURES ASSOCIATED WITH CONGENITAL ABNORMALITIES 579

Figure 22. Congenital lip pits in van der Woude syndrome.

characteristic bilateral pits or cysts of the lower lip occur (Fig. 22). Families
with these pits are at a high risk for cleft lip with or without lip pits, which are
inherited together or separately in an autosomal dominant fashion. Families
should be counselled for this. 5 In general, cleft lip or palate is considered to
be the result of a multifactorial pattern of inheritance, and data suggest that
some isolated clefts of the palate may have a similar etiology. 2 ° Cleft uvula
may be a microform of cleft palate and, as such, is listed with cleft palate in
Table 9. Bifid uvula, however, also occurs in a greater frequency in families

Figure 23. Bifid uvula.

580 RAY E. STEWART AND ANDREW E. POOLE

with histories of cleft lip and palate (Fig. 23). These data seem to contradict
the concept that cleft lip and cleft palate have a separate etiology. 20
High arched palate seems to be described in conjunction with almost
every craniofacial syndrome in which narrowing of the maxilla is evident. A
particularly high-arched palate with crowding of the dentition and an open
bite anteriorly is present in Apert syndrome and cleidocranial dysplasia.
Apert is further characterized by craniosynostosis and syndactyly. Cleido-
cranial dysplasia (dysostosis) syndrome has additional findings of aplasia of
the clavicles, late closure of cranial sutures with wormian bones, and
supernumerary teeth.
Soft tissues of the oral cavity listed in Table 9 include abnormalities of
the frenula and abnormal gingiva. The frenula associated with OFD I and
II have been discussed earlier. Characteristic multiple frenula extending
over the alveolar ridge and giving it a lobular appearance in the newborn is a
feature of Ellis-van Creveld syndrome (chondroectodermal dysplasia). These
children also have neonatal teeth (25 per cent), severe prenatal growth delay
with mesomelic dwarfism, ectodermal dysplasia (especially of the nails), and
congenital heart defects ·(50 per cent of cases).
Gingival abnormalities are of two broad general categories: those with
periodontal disease and those with gingival hyperplasia or overgrowth.
Periodontal diseases are very common in the adult population, and 90 per
cent or greater have gingival inflammatory disease with gradations from
simple gingivitis to advanced periodontal disease with alveolsr hone loss and
tooth mobility. The bacterial origin of these diseases is undoubted. Advanced
periodontal disease in children is seen in several conditions but most
noteworthy from a syndrome point of view is Type VIII Ehlers-Danlos
syndrome and Papillon Lefevre syndrome. Ehlers-Danlos syndromes in
general are associated with periodontal disease but the recently described
Type VIII syndrome appears to be a condition with minimal joint and skin
involvement but significant periodontal disease. Papillon Lefevre syndrome
is a condition in which significant bone loss is noted around teeth that
ultimately leads to their loss. It is a progressive disease that affects the
primary and permanent dentition and is concurrently associated with hyper-
keratosis of the palms, soles of the feet and elbows, and so on. It has an
autosomal recessive inheritance pattern. The only effective treatment to date
appears to be to remove all the erupted teeth and to use aggressive anti plaque
prevention as new teeth erupt.
Gingival enlargement is commonly associated with the taking of pheny-
toin, with isolated hereditary gingival fibromatosis, and with several blood
dyscrasias. It is also seen in Cowden syndrome, a condition characterized by
multiple neoplastic lesions in the breast, thyroid, ovaries, and so on and with
papillomatous lesions of the gingiva, palate, and tongue. This is an autosomal
dominant syndrome.
Mandibular defects can be classified as micrognathia, asymmetrical bone
growth, or as overgrowth of the mandible or prognathism.
Micrognathia is again a common feature of many syndromes. Smith23 lists
over 50 in which this condition is frequently or occasionally a feature. Many of
these have already been discussed and a few of the common ones are listed in
Table 9. Of particular note again is the Robin anomaly, discussed earlier in
0ROFACIAL STRUCTURES ASSOCIATED WITH CONGENITAL ABNORMALITIES 581
which abnormal development of the mandible prenatally is believed to be a
cause of this abnormality. Micrognathia is also a characteristic of a group of
conditions known as first arch syndromes. The mandibular arch embryologi-
cally is largely responsible for development of the lower jaw with its attached
muscles, nerves (fifth cranial nerve), and blood vessels (maxillary artery).
Meckel's cartilage is the embryonic inducer of the mandible and is retained
postnatally in the growing condylar head and in the malleus of the middle ear.
Thus, micrognathia is commonly associated with abnormalities of the external
or middle ear, including middle ear deafness, absence of the external auditory
meatus and external ear abnormalities. Microforms of these syndromes are
seen as low set and/or small rotated ears often with ear tags. Treacher-Collins
syndrome (mandibulofacial dysostosis) is a prototype of this type of defect.
Most first arch defects are diagnosed as part of specific syndromes such as this
but the grouping of these first arch characteristics is often useful in the
diagnosis of craniofacial syndromes.
The Hallermann-Streiff syndrome is marked by micrognathia with very
short rami, brachycephaly with frontal bossing, microstomia and flattening of
the midface over the zygomatic bones with a small thin nose. The condition is
also associated with growth delay and a variety of ocular defects that often end
in blindness. Hypoglossia (aglossia)-hypodactylia was discussed earlier.
Asymmetric mandibular development is often seen with abnormalities
involving unilateral condylar development and abnormal growth on the
affected side. Hemifacial microsomia is the commonest type of this abnormal-
ity and is often seen with abnormal external or middle ear development on the
affected side. This defect is now considered to be a lesser form of facioauri-
culovertebral anomalad (Goldenhar syndrome) in which vertebral and rib
defects are commonly seen. The anomalad appears to be sporadic, although
70 per cent of cases occur in males. Occasionally, eye defects and other
abnormalities are seen, including mild mental retardation, but as simple
hemifacial microsomia it responds well to early and repeated surgical inter-
vention. Asymmetric mandibular development is also seen in the Klippel-
Trenaunay-Weber syndrome if the craniofacial structures are involved. This
syndrome is associated with multiple hemangioma and commonly involves
the limbs. Involvement of the orofacial structures often leads to delayed
eruption or shedding of the teeth and enlargement of the tongue only on the
affected side (Fig. 24).
Prognathic jaw is often considered to be an isolated autosomal dominant
characteristic that is common in males and can also result from late-onset
hyperpituitary syndrome. It is also seen in acrodysostosis in association with
small dysostotic hands and some growth delay.
Hypoplasia of the maxilla leads to significant midfacial flattening with
pseudoprognathism. Maxillonasal dysplasia is a clear example of flattening of
the midface region involving both the maxillary and nasal bones with
significant concave facial profile, or "dish" face. This is usually a benign
condition (apart from the psychological difficulties in severe cases, associated
with teasing in school) that can be treated with surgery in the post-growth
years. It occasionally is associated with aero-osteolysis of the terminal
phalanges of the hands, which might lead to short fingers. It is to be
distinguished from frontonasal dysplasia or median cleft syndrome, a syn-
582 RAY E. STEWART AND ANDREW E. POOLE

Figure 24. Lower jaw of patient, age 14 years, with Kippel-Trenaunay-Weber syndrome. Note
the delayed dental development on the affected side.

drome with very severe hypertelorism and occasionally associated with

midline central nervous system abnormalities. A true midline cleft may exist
in this condition or it may result only in mild nasal notching.
The other syndromes listed in Table 9 have been discussed elsewhere
with the exception of the de Lange syndrome. This is a syndrome with a broad
range of expression but is most often associated with significant growth delay,
moderate to very severe mental retardation, limb reduction deformities,
and/or small feet and characteristic facies. The face involvement consists of
bushy, confluent eyebrows; small, upturned nose; small, downturned mouth
with a midline point; hirsutism; micrognathia; and some midfacial deformity.
Infants are often noted to have a low-pitched cry and neonatal microcephaly.
Although considerable variation exists in the facial appearance of infants with
de Lange syndrome, the face plays an important role in the diagnosis of this
often severe disorder.
The oral opening can be described as very small (microstomia) or very
large (macrostomia). Even in very small, young infants, the mouth can be
opened to a vertical distance of 2V2 to 3 em. The intercommissural distance
varies from a mean of 27 mm in infancy to 50 mm in adulthood, 4 with girls
generally having smaller measurements than boys at any given age. Although
these measurements are often difficult to perform on conscious children, they
do give some point of reference for the assessment of these pathologic stigma-
ta.
Otopalatodigital syndrome is a condition manifested by deafness, cleft
palate, and characteristic hands and feet having short, broad phalanges and
curved toes and fingers. The oral opening is generally small and associated
0ROFACIAL STRUCTURES ASSOCIATED WITH CONGENITAL ABNORMALITIES 583
with midfacial hypoplasia but characteristic lateral supraorbital bossing. It is
an X-linked dominant condition with semidominant expression in females.
The Robinow syndrome (fetal face syndrome) 23 is also associated with
midfacial flattening and a small, bow-shaped oral opening. Microcephaly is
common with a large anterior fontanelle that closes late. Shortening of the
forearms and abnormal genitalia are characteristic. Hallermann-Streiff syn-
drome, in which microstomia is also common, was discussed earlier.
A large mouth is usually the result of failure of fusion of the embryonic
maxillary and mandibular processes in early prenatal development. In the
mucopolysaccharidoses, however, the large oral opening may be secondary to
the enlargement of the soft tissues, especially the tongue, and is not particu-
larly diagnostic of these conditions. As an embryologic defect, macrostomia
can be an isolated event of part of the teratogenic effects involving all of the
first arch derivatives. Relative macrostomia is found occasionally in the
facioauriculovertebral anomalad discussed earlier.
In these discussions, very little mention has been made of the oral
findings in chromosomal abnormalities, although a few have been listed in
Table 9. Any infant born with congenital anomalies involving multiple organ
systems should be considered for cytogenetic examination. Except in a few
cases -for example, Down syndrome- the craniofacial stigmata are not
sufficiently characteristic or carefully enough delineated to be diagnostic by
themselves and have therefore not been discussed here. The reader is
referred to the excellent atlas of Goodman and Gorlin 12 for clear illustrations
of the craniofacial and other characteristics of the many chromosomal abnor-
malities. Other excellent texts in this and all areas of syndromology are listed
in the references and this article serves only as a guide to these more
comprehensive volumes.

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3. Bixler, D.: Heritable disorders affecting dentin. In Stewart, R. E., and Prescott, G. H. (eds.):
Oral Facial Genetics. St. Louis, C.V. Mosby Co., 1976.
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15. Johnston, M. C., and Pratt, R. M.: The neural crest in normal and abnormal craniofacial
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