PERMANENT CANINE AGENESIS IN DOWN SYNDROME

ARTICLE

ABSTRACT Distribution of permanent canine

The purpose of this study was to
investigate the distribution of permanent
canine agenesis in subjects with Down
syndrome (DS). Subjects with canine
agenesis were determined by means of
panoramic radiographs from 150 DS
subjects attending a center for special
care dentistry. Our results confirm the
high prevalence of agenetic canines in
DS (21 canines, 14%). We found spe-
cific effects on the distribution both of
phenotype and of location (jaw). In
subjects with a mild expression of
hypodontia (phenotype nonoligodontia)
agenetic canines primarily occurred in
the mandibula, whereas in subjects with
severe hypodontia (phenotype oligodon-
tia) agenetic canines virtually only
occurred in the maxilla. In both pheno-
types cooccurrence of an agenetic
lateral incisor with an agenetic canine
was observed in the maxilla. It was strik-
ing that canine agenesis in the
mandibula did not cooccur with agene-
sis of other teeth. These results can be
important for treatment planning.
KEY WORDS: Down syndrome,
hypodontia, oligodontia, canines
agenesis in Down syndrome: 15 cases
from a Centre for Special Care Dentistry
Wimke Reuland-Bosma;1* Merijn C. Reuland;2 Ewald Bronkhorst3
1Centrefor Special Care Dentistry, CBT Rijnmond in Rotterdam, The Netherlands; 2Physician,
Department of Internal Medicine, VU University Medical Center Amsterdam, The Netherlands;
3Department of Cariology and Preventive Dentistry, Radboud University Nijmegen Medical Centre,
The Netherlands.
*Corresponding author e-mail: wimke@reuland.nl, wimke.reuland@gmail.com
Spec Care Dentist 35(2): 78-82, 2015
In t r od uct ion
Many dental anomalies in subjects with Down syndrome (DS; trisomy 21) have been
reported worldwide. Abnormalities in number (hypodontia), size (smaller), morphol-
ogy (peg shaped), and late development of their dentition are often observed.1,2 The
prevalence of agenesis (usually bilateral) of permanent teeth (excluding the third
molars) has been reported to be higher in children with DS than in normal children;
the results given vary from 30%3 to 60%.4 The pattern of agenesis in the maxilla, as
reported in the literature about DS, has been found to be identical to the pattern seen
in normal children, with agenesis of the lateral incisors being most frequent, followed
by the second premolars. In the mandibula the pattern is different. Whereas central
and lateral incisors are less affected by agenesis in normal European children, agenesis
of the central or lateral incisors (or both) has often been reported in DS, in addition to
agenesis of the second premolars.2,5,6 When both central lower incisors are agenetic in
DS, this appears to be a predictor for a more severe disorder, namely the subsequent
development of oligodontia.7

The phenotype oligodontia is charac- central incisors, and their agenesis is

terized by the congenital absence of six
or more permanent teeth, excluding the
third molars,8 whereas non-oligodontia is
characterized by the congenital absence
of 1 up to 5 teeth. Note that the contrast
between the phenotypes oligodontia
versus nonoligodontia is not only quanti-
tative but also qualitative.8
Several investigators have reported
agenetic canines in DS.2,4–7,9,10 In people
without syndromes canines are among
the least affected teeth in the dentition.
For example, in a Hungarian population
a prevalence of 0.29% has been
reported.11 Canines are generally consid-
ered stable teeth, along with the upper
rare.12
The purpose of the present study was
to shed light on the factors determining
the distribution of permanent canine
agenesis in DS. In order to do so we
focused on (1) the distribution over DS
subjects with oligodontia versus nonoli-
godontia; and (2) the differences in
distribution of canine agenesis between
the jaws.
Ma t er ia l a nd m e t h o d s
This was a retrospective cross-sectional
study. The sample consisted of 150 indi-
viduals with DS (82 male and 68 female).

© 2014 Special Care Dentistry Association and Wiley Periodicals, Inc.

78 S p e c C a r e D e n t i s t 3 5 ( 2 ) 2 0 1 5 DOI: 10.1111/scd.12086

scd12086.indd 78 13/02/15 11:15 AM

 PERMANENT CANINE AGENESIS IN DOWN SYNDROME
Figure 1. Distribution of agenetic teeth in subjects with DS: Total group (150 subjects) with 355
agenenetic teeth, ranging from 0–15 per subject.
All were referred to the Centre for Special
Care Dentistry, CBT Rijnmond, in
Rotterdam, The Netherlands, by general
practitioners. All participants gave
informed consent (in the case of DS sub-
jects by parent or guardian) in
accordance with the ethical principles of
the world medical association declaration
of Helsinki 2002. The age of the subjects
was 7.03 to 26.35 years (mean 16.63
years; SD 4.8 years). Two patients below
the age of 9 years were included in the
study, because calcification of the premo-
lars was already finished. From each
subject, a standardized record was
obtained, including a detailed clinical
examination with panoramic radio-
graphs. During dental treatment under
general anesthesia, a standardized roent-
gen set was made after written parental
informed consent was obtained.
Permanent teeth that were hypoplastic or
radiographically observed, but not yet
erupted, were considered to be present.
For registration the FDI numbering
system was used. Absent teeth were reg-
istered by tooth number.13 For the
descriptive statistics agenetic teeth were
represented in a histogram (Figure 1).
R es u lts
In the whole group of DS persons in
this study (n = 150) a total of 355 teeth
Reuland-Bosma et al.
scd12086.indd 79
were agenetic, ranging from 0 to 15 per
subject. The group consisted of 82 males
and 68 females. In 58 subjects no
agenesis was observed, whereas 92
subjects (61.3%) had one or more
agenetic teeth (Figure 1). The latter
group was divided in two subgroups,
one with oligodontia (23 subjects), the
other with nonoligodontia (69 subjects).
In both groups, agenesis of one or more
permanent canines was observed
(7 subjects in the nonoligodontia and 8
subjects in the oligodontia group) with a
total number of 21 agenetic canines in
15 subjects for the whole group n = 150
(14%). In Table 1, the 15 subjects are
listed by sex, differentiating between uni-
and bilateral absence of canines. Given
the FDI numbering system, the jaw posi-
tion of the agenesis can be read off the
table (upper/lower and right/ left).
Cooccurrence of agenetic canines with
other congenitally agenetic teeth was
recorded.
Evaluation of the pattern of
canine agenesis in DS
In both groups: The frequency of agenesis
of canines in DS was generally higher in
males than in females (10/5) with a pref-
erence for agenesis to the left side of the
jaw compared to the right side (14/ 7). A
certain preference for unilateral com-
pared to bilateral canine agenesis was
observed (9/6) whereas small differences
were also observed between the upper
and lower jaw (12/ 9).
Table 1 shows the following striking
differences between the two groups:
- In the nonoligodontia group, in addi-
tion to an agenetic canine, in only
one of the seven subjects more than
two other teeth were agenetic.
Furthermore, the agenetic canines
were predominantly present in the
lower jaw with no real preference for
unilateral or bilateral absence and for
the left or right side.
- In the oligodontia group, as can be
expected, in addition to the agenetic
canine, several other agenetic teeth
were observed. But, what does not
follow from being oligodontic per se,
is that this group was characterized by
a predominantly unilateral absence of
the canines, with frequent agenesis on
the left side of the jaw. Furthermore,
all agenetic canines were located in
the upper jaw (except 1).
D is cus s ion
Our finding that tooth agenesis
(hypodontia) occurs in (61.3%) of the
total DS group (n = 150) agrees with the
results in recent studies of DS popula-
tions within different countries.4,9,14
The prevalence of hypodontia depends
on the population studied. One of the
relevant factors is the country, but
another possible factor influencing
findings is the amount of subjects with
oligodontia. In our study, the group with
oligodontia consisted of 23 subjects. In
one subject even 15 agenetic teeth were
observed. The group with less severe
hypodontia (the nonoligodontia group),
consisted of 69 subjects. Agenesis of the
permanent canines was observed in both
groups; that is, in the nonoligodontia (7
subjects) as well in the oligodontia group
(8 subjects).
The upper canines are considered
stable teeth along with the upper central
incisors and the first molars.12 However,
it has been established that this does not
hold for all populations. For example,
agenetic canines combined with agenesis
of other tooth types have been observed
S p e c C a r e D e n t i s t 3 5 ( 2 ) 2 0 1 5 79
13/02/15 11:15 AM
 PERMANENT CANINE AGENESIS IN DOWN SYNDROME

Unlike in these and other studies, the

Table 1. Prevalence and distribution of permanent agenetic
canines in cooccurrence with other agenetic teeth. present investigation allowed us to split
the population according to phenotype.
Nonoligodontia: total subjects 69, 7 subjects with 11 agenetic canines
We found that both phenotypes were
Gender M/F Cooccurrence Right Left Uni/bilateral represented among the subjects with age-
agenetic teeth netic canines. Therefore we were able to
F 0 43 Unilateral compare the locations of the canines in
F 2 12, 15 both phenotypes. Interestingly, the loca-
33 Unilateral
tions of the agenetic canines were not
equally distributed over the jaws in the
M 2 15 25
different phenotypes.
43 33 Bilateral In the phenotype nonoligodontia the
M 0 43 33 Bilateral agenetic canines were found especially in
M 4 23, 22 Unilateral
the mandibula whereas the agenetic
canines in the phenotype oligodontia
41 31, 32
occurred in the maxilla. The latter
M 0 43 33 Bilateral phenotype is thought to be primarily
M 2 13, 12 23, 12 Bilateral influenced by genetic factors and is not
Oligodontia: total subjects 23, 8 subjects with 10 agenetic canines
an isolated phenomenon, but rather a
polymorphism related to the prevalence
M/F Co-occurrence Right Left
of other missing teeth (the timing of
agenetic teeth
tooth calcification).12,17
M 11 13, 12, 15 23, 24, 25 Bilateral In the phenotype oligodontia, nine
41, 44, 45 31, 32, 34, 35 upper agenetic canines (mostly unilateral,
M 4 13, 12 23, 22 Bilateral 6×), cooccurred with 63 other agenetic
teeth. The only agenetic canine in the
41 31
mandibula was the result of a fusion of
F 8 14, 15 24, 25 two deciduous teeth (63 and 62) result-
42, 45 33, 35 Unilateral ing in agenesis of the permanent canine,
M 6 15, 17 23, 25, 27 Unilateral a phenomenon also observed by others.16
45 35
The pattern we observed fits in with the
literature on dental development.
F 14 12, 15, 17 23, 22, 25, 27 Unilateral
According to the theory of Brook,12 as
41, 42, 45, 47 31, 32, 35, 37 tooth size is reduced, a threshold is
M 6 13, 14 23, 22, 24 Unilateral crossed, at which point agenesis occurs.
45 32
Sofaer et al.18 suggested that the greater
variability within each morphological
M 8 12, 15 23, 22 Unilateral
class that is seen in teeth that form later,
41, 42 31, 32, 35 may be the result of the interaction of
F 6 12, 17 23, 22, 27 unilateral tooth germs during development. Bazan
41 31 MT19 showed two cases of maxillary
canine agenesis and peg-shaped laterals,
and suggested that, since maxillary per-
manent canines develop before lateral
in Japanese orthodontic patients.15 right side of the jaw. This is in agreement incisors, the absence of the canine might
Interestingly, in our study the same pat- with Russell and Kjaer.6 sufficiently alter the local environment at
tern can be seen. Over the whole population of our the time of the development of nearby
Notwithstanding the stability of the investigation, agenesis of canines unstable teeth, so that these reduce
canines, agenesis of the canines in DS is occurred in both the maxilla and the themselves to smaller teeth. Delayed
a frequent finding described by several mandibula. This agrees with several development of the teeth adjacent to the
authors in different countries.1,2,4–6,9,10 other studies,1,2,6,9 although some studies site of the agenesis was also observed by
Our own findings (Table 1) show that reported agenesis only in the maxilla.4,10 Uslenghi et al.20 In this phenotype, age-
the frequency of tooth agenesis is higher The latter studies, however, do not netic canines cooccurred with an agenetic
in males than in females, and that agene- provide us with the information needed lateral incisor in 7 of the 9 cases, which
sis occurred more to the left than to the to determine the phenotypes involved. supports the theory of interaction of

80 S p e c C a r e D e n t i s t 3 5 ( 2 ) 2 0 1 5 Permanent canine agenesis in Down syndrome

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 PERMANENT CANINE AGENESIS IN DOWN SYNDROME
tooth germs during development. In a
Chinese population a tendency toward
the same effect has been observed by the
occurrence of 5 microdontic maxillary
lateral incisors in 32 cases with agenetic
maxillary canines.21 In general, different
types of agenetic teeth are more fre-
quently found in the maxilla compared to
the mandible, which is explained by the
fact that maxillary and mandibular teeth
are genetically determined independently
during morphogenesis, together with the
fact that the nature of the molecular sign-
aling in the upper and the lower jaw may
vary.22 In this light, the results of the pro-
cesses in the lower jaw can be expected
to be different, in accordance with our
findings.
In the phenotype nonoligodontia
agenesis of the canines occurred more in
the mandible (8×) compared to maxilla
(3×). Furthermore, in this phenotype
agenesis of the canines in the upper jaw
cooccurred with agenesis of the lateral
incisors. In contrast, this phenomenon
was not seen in the mandible, whereas
agenesis of the lower lateral incisors is
frequently found in DS.1,4,7 They were
solitarily absent, unilaterally or bilater-
ally (3×), an observation well known
from the literature.2,3,9 Striking was the
fact that agenetic canines in the mandib-
ula did not cooccur with other lateral
agenetic teeth. This, again, patterns with
what is known about dental develop-
ment. The average delay in calcification
in DS is around 0.7 years in DS.23 In a
normal population there is histological
evidence of mineralization of the lower
canine between the third and sixth
months with a much slower rate of
growth.24 Disturbing factors in the local
environment can play a role and, when
the time window is extended, they have
more time to exert their negative influ-
ence. This can lead to effects such as less
developed peripheral nerve branching,
local diminished blood supply, or to both
acting together. This, then, may lead
more easily to canine agenesis in this
jaw.5,6,25,26
In the “total group with canine agene-
sis” the upper lateral agenetic incisor
cooccurred 9 times with an agenetic
canine; a much higher percentage of age-
Reuland-Bosma et al.
scd12086.indd 81
netic lateral incisors (60%) was found
than normally (24%) in DS.4 In general,
solitary agenetic canines in the small
maxilla in DS do not give rise to clinical
problems, but the presence of “a combi-
nation of agenesis of lateral incisor and
agenesis of the canine” in the same jaw is
of utmost clinical relevance. Timely
screening with the use of panoramic
radiographs makes adequate treatment
planning possible. For example, early
treatment with or without orthodontic
intervention, guiding teeth to their
optimal positions.
Conclusions
Our results confirm the high prevalence
of agenetic canines in subjects with DS.
The prevalence and distribution of these
agenetic canines was different for the
two phenotypes nonoligodontia and
oligodontia. In the latter phenotype
surprisingly many agenetic canines were
observed in the maxilla often together
with an agenetic lateral incisor. In the
phenotype nonoligodontia, a similar
cooccurrence of an agenetic canine and
a lateral incisor was seen in the maxilla
(2 subjects). In the mandibula, by con-
trast, agenetic canines did not cooccur
with other agenetic teeth. Solitary
absence was the rule in the five subjects
with agenetic canines (3× bilateral and
2× unilateral). Presumably local distur-
bances have been responsible.
Future research should evaluate the
agenesis of canines in the mandibula. A
careful description of the canines in the
mandibula may help to shed further light
on the disturbed pattern observed in DS.
Co nf l ict s of int er es t
The authors declare no conflicts of interest.
Approved statement that subjects gave
informed consent to the work.
Acknowledgements
This investigation was supported by a
grant from the VBTGG (Vereniging tot
Bevordering der Tandheelkundige
Gezondheidszorg voor Gehandicapten, a
society for research development of
dental health in people with disabilities
in the Netherlands). The grant was
awarded to the first author.
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