Eur Arch Paediatr Dent (2013) 14:279–288
DOI 10.1007/s40368-013-0082-z
REVIEW
Aetiology of supernumerary teeth: a literature review
R. P. Anthonappa • N. M. King • A. B. M. Rabie
Received: 10 October 2012 / Accepted: 14 February 2013 / Published online: 26 September 2013
Ó European Academy of Paediatric Dentistry 2013
Abstract
Background Supernumerary teeth are teeth, or tooth-like
structures that have either erupted or remain unerupted in
addition to the 20 primary and 32 permanent teeth.
Aims This paper attempts to (a) provide an overview of
the proposed hypotheses and the current understanding of
the aetiology of supernumerary teeth, and (b) review the
published cases of supernumerary teeth occurring in
families.
Review No studies have been able to distinguish between
different aetiologies for the different locations of super-
numerary teeth, while, from a developmental or molecular
perspective, the proposed hypotheses may be plausible and
explains the origin of different types of supernumerary
teeth.
Conclusion The only clearly evident feature, based on the
existing published reports, is that it is logical to state that
supernumerary teeth have a genetic component in their
aetiology.
Keywords Aetiology
Supernumerary teeth

Hyperdontia
Genes
Heredity
R. P. Anthonappa (&)
N. M. King
School of Dentistry, Faculty of Medicine, Dentistry and Health
Sciences, The University of Western Australia,
17 Monash Avenue Nedlands, Perth, WA 6009, Australia
e-mail: robert.anthonappa@uwa.edu.au
A. B. M. Rabie
Private Practice, Hong Kong, SAR China
Introduction
Supernumerary teeth are teeth, or tooth-like structures that
have either erupted or remain unerupted in addition to the 20
primary and 32 permanent teeth. They represent a unique
developmental anomaly of pattern and morphogenesis that
occurs in the tooth bearing areas of both dental arches. They
may be single, multiple, unilateral or bilateral in their dis-
tribution, and frequently occur in the premaxilla (Anthon-
appa et al. 2008). They cause a range of dental complications
from tooth crowding, midline diastema to dentigerous cyst
formation (Garvey et al. 1999; Proff et al. 2006; Sanei-
Moghaddam et al. 2009). Although several authors, anec-
dotally, have proposed either early or delayed removal of
supernumerary teeth, recent evidence (Omer et al. 2010)
suggests that for unerupted anterior supernumerary teeth
early surgical removal seems to be optimal from 6.1 to
7.0 years after which time more complications occur.
Although several hypotheses have been proposed, the
aetiology of supernumerary teeth remains unclear. To date,
there is neither evidence nor template to indicate the tim-
ing, or pattern of formation of supernumerary teeth. They
may form in the primary, mixed or permanent dentitions;
this is probably the reason why they are identified sub-
sequent to the occurrence of associated complications. In
recent years, remarkable advancements in the field of
molecular genetics have improved our understanding of the
different mechanisms involved in tooth formation and
development. Therefore, this paper attempts to provide an
overview of the current knowledge on the aetiology of
supernumerary teeth. It is intended to review the hypoth-
eses that have been proposed to explain the occurrence of
supernumerary teeth. Furthermore, a review of published
cases of supernumerary teeth occurring in families will be
presented.
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Proposed hypotheses for the aetiology
of supernumerary teeth
Atavism
It is defined as ‘‘the recurrence of ancestral conditions in a
species, or the reversion to ancestral type’’ (Osburn 1912).
In other words, it is a sort of long-distance heredity or
phylogenetic reversion to extinct primates. Originally, it
was theorised that supernumerary teeth formation was
nature’s way of restoring teeth that had been lost during the
process of evolution. Nevertheless, this concept is largely
rejected because: (1) a second canine in man or lower
mammals cannot be attributed to reversion, since there is
no ancestral condition to which it could revert, (2) a third
incisor, a third premolar, or a fourth molar can only be
attributed to reversion if it covers an extremely long period
of time; approximately four million years, and this goes
beyond mammalian types, this alone is insufficient to
render valid support to this theory, (3) supernumerary teeth
develop in ectopic positions, are dysmorphic in shape and
usually occur in isolation, and (4) the paleontological
record of the evolution of teeth in all mammalian orders
lends no support to atavisms when applied to supernu-
merary teeth.
Embryologic aberrations
Several theories attribute the development of supernumer-
ary teeth to aberrations during embryologic formation
which include: dichotomy of tooth germs, hyperactivity of
the dental lamina, and remnants of epithelial cells.
Dichotomy
The word dichotomy means splitting of a whole into two
parts which can be either equal or unequal. Therefore, this
concept postulates that a division or split in the developing
tooth bud can give rise to supernumerary teeth (Black
1909; Bateson 1982). These divisions may occur sub-
sequent to aberrations during embryonic formation (Black
1909), or trauma (Ranta and Ylipaavalniemi 1981). A
complete, equal division of the tooth bud would result in a
supplemental or duplicate tooth, while an unequal split
would give rise to one normal tooth and another with rel-
atively small dimensions (Osburn 1912).
The bones of the pre-maxilla and in the inter-maxillary
regions exhibit a wide variation. Most often, the incisive
suture terminates at the alveolus adjacent to the canine
(50 %), between the canine and lateral incisor (42 %), or
between the canine and first premolar (5 %). Furthermore,
the presence of the numerous foramina and canals in this
region combined with the complex mechanism of union of
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Eur Arch Paediatr Dent (2013) 14:279–288
the various bony processes makes the developing tooth
buds in the pre-maxilla susceptible to division (Saarenmaa
1951).
Few animal studies (Kerley and Kollar 1977) have
demonstrated that trauma can stimulate the proliferating
epithelial remnants, which are mainly derived from the
Hertwig’s root sheath, and remain in the inter-septal areas
to differentiate into cells that give rise to supernumerary
teeth. Furthermore, Ranta and Ylipaavalniemi (1981)
reported two patients with a history of mandibular fracture
in the premolar region who, years later, developed super-
numerary teeth adjacent to fracture lines.
Although there is some evidence to suggest a cause-and-
effect relationship between jaw fractures and supernumer-
ary teeth, one cannot rule out the possibility of these
findings being a mere coincidence, as there appears to be
no quality evidence in the literature to support this concept.
Furthermore, mandibular supernumerary premolars fre-
quently occur in patients without a history of jaw fracture;
thus, rendering this hypothesis unrealistic.
Hyperactivity of the dental lamina
Based on embryological studies, Black (1909) proposed an
explanation for the formation of supernumerary teeth
which has been widely accepted by investigators. Briefly
stated, the enamel organ is the most important structure in
tooth formation as it is the first rudiment to appear, and its
presence conditions the formation of dentinal papilla in the
connective tissue. This enamel organ arises from the pro-
liferation of the dental lamina, which is a continuous plate
of cells derived from the embryonic oral epithelium. Fur-
thermore, the size and form of the papilla and subsequently
that of the tooth depend on the size and form of the enamel
organ. If the proliferation occurs in a regular order and
number, the constituents of the dental series will develop in
an orderly fashion, both in number and location.
The chord of cells which arise from the dental lamina,
that subsequently give rise to the enamel organ, are not
always limited to a single proliferation for each tooth of the
normal series, instead accessory rods are often observed.
However, any proliferation of the epithelial cells from the
lamina, if of sufficient size, could penetrate deeply into the
tissues to give rise to an enamel organ and consequently to
a tooth.
Alternatively, the epithelial cord which precedes the
enamel organs of the permanent teeth normally disappears.
However, it may fail to resorb completely following the
closure of the follicle, thus allowing the epithelial remnants
to persist. These remnants are also known as epithelial
whorls. If these epithelial whorls or remnants are large
enough, they are capable of exciting and controlling the
development of the dental papilla.
Eur Arch Paediatr Dent (2013) 14:279–288 281

Table 1 Published case reports of supernumerary teeth occurring in siblings

References Country Ethnicity Siblings Supernumerary teeth
Total Affected Age Arch Tooth type Number
(gender) (years)

Brodie (1936) USA – 3 Sib 1 (male) 10 Both Mesiodens, Premolars Multiple

Sib 2 (female) [10 Both Mesiodens Double
Sib 3 (female) \10 Maxilla Mesiodens Single
Molleda Medrano (1956) Spain – 2 Sib 1 (male) – Maxilla Mesiodens Single
Sib 2 (male) – Maxilla Mesiodens Single
Nadal-Valldaura (1961) Spain – 2 Sib 1 (male) 12 Maxilla Mesiodens Single
Sib 2 (male) 11 Maxilla Mesiodens Single
Sedano and Gorlin (1969) USA – 2 Sib 1 (male) – Maxilla Mesiodens Single
Sib 2 (female) – Maxilla Mesiodens Single
Mercuri and O’Neill (1980) USA – 2 Sib 1 (female) 17 Both Premolars Multiple
Sib 2 (female) 15 Both Premolars Multiple
Konttinen et al. (1984) Finland 3 Sib 1 (female) 13 Both Premolars, molars Multiple
Sib 2 (female) 18 Both Premolars, molar Multiple
Sib 3 (female) 22 Maxilla Molar Single
Almeida et al. (1995) Brazil Caucasian 3 Sib 1 (male) 11 Maxilla Mesiodens Single
Sib 2 (female) 9 Maxilla Mesiodens Single
Sib 3 (female) 21 months Maxilla Mesiodens Single
Scanlan and Hodges (1997) UK African 2 Sib 1 (female) 12 Mandible Premolar Single
Sib 2 (male) 13 Both Premolar Multiple
Desai and Shah (1998) India – 2 Sib 1 (male) 25 Both Mesiodens, Premolars, Multiple
Sib 2 (male) 36 Both Paramolars Multiple
Mesiodens, Premolars,
Paramolars
Marya and Kumar (1998) India – 2 Sib 1 (male) 12 Maxilla Mesiodens Single
Sib 2 (male) 8 Maxilla Mesiodens Double
Gallas and Garcı́a (2000) Spain – 2 Sib 1 (female) 13 Maxilla Mesiodens Double
Sib 2 (female) 8 Maxilla Mesiodens Double
Inchingolo et al. (2010) Italy Caucasian 3 Sib 1 (male) 30 Both Molars Multiple
Sib 2 (female) 17 Both Molars Multiple
Sib 3 (female) 13 Maxilla Molars Multiple
Sib sibling

Therefore, supernumerary teeth can arise from one of
the two sources: (1) supernumerary buds given off from the
band of epithelium, or the epithelial cords of the buds that
form normal teeth, and (2) persistent whorls of epithelial
cells that are formed during the disintegration of the epi-
thelial cords.
Progress zone theory
Following the works of Osborn (1978), Lumsden (1979),
and Schwartz (1984), it was proposed that supernumerary
teeth could result from the progress zones of a proliferating
tooth series that continue to produce teeth at the end of that
particular series. Therefore, a supernumerary tooth would
be evident either anterior or posterior to the normal incisor,
canine or molar tooth series. This hypothesis is supported
by a small number of studies that are based on specimens
of anthropoid primates (Schwartz 1984).
Unified aetiology
This hypothesis was proposed by Brook (1984). Based on a
multi-factorial model, this hypothesis exhibits a continuous
scale and thresholds, related to the tooth size and number.
The cumulative effect of both genetic and environmental
factors determines the position on the scale. This polygenic
quasi-continuous traits model explains the possibility of
simultaneous occurrence of supernumerary teeth and other
dental anomalies such as megadontia, oligodontia and
microdontia. Occasionally, a chromosomal or a single gene

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Table 2 Published case reports of mesiodens occurring in twins

References Country Ethnicity Zygosity Gender Distribution of
mesiodens between the twins

Gysel (1963) Belgium – Monozygous Female Mirror image discordant

Dizygous Female
Hunstadbråten (1965) Norway – Monozygous Male Mirror image
Schön (1974) Germany – Monozygous Male Concordant
Bucci and Martina (1975) Italy – Monozygous Female Discordant
Cadenat et al. (1977) France – Dizygous Female Discordant
Carton and Rees (1987) UK Caucasian Monozygous Male Mirror image
Choi et al. (1990) China Chinese Monozygous Male Near concordant
Seddon et al. (1997) UK Afro-Caribbean Monozygous Male Near concordant
Sharma (2008) India – Monozygous Male Discordant
Babacan et al. (2010) Turkey – Monozygous Male Concordant
Sumida et al. (2010) Japan – Monozygous Female Concordant

Table 3 Published case reports of other types of supernumerary teeth other than mesiodens occurring in twins
References Country Ethnicity Zygosity Gender Supernumerary teeth Supernumerary teeth
distribution between
the twins

Rubin et al. (1981) USA Black Monozygous Male Supplemental premolars Discordant
Beere et al. (1990) Namibia – Monozygous Male Supplemental primary incisor Mirror image
Jasmin et al. (1993) France Caucasian Monozygous Male Supplemental premolars Mirror image
Langowska-Adamczyk Poland – Monozygous Male Canine, premolars, molars Concordant
and Karmanska (2001)

anomaly can exert a major effect which explains the
occurrence of supernumerary teeth in the presence of other
dental anomalies.
Heredity
The literature holds a wealth of reports to support the
concept of familial predisposition to supernumerary teeth
with an increased number of supernumerary teeth evident
in the relatives of those affected. Recently, based on a
questionnaire study, Kawashima et al. (2006) reported that
if either of the parents exhibited a supernumerary tooth,
then the child had a 5.9 times higher risk of developing a
supernumerary tooth compared to parents who did not have
a supernumerary tooth. Supernumerary teeth occur more
commonly in males than females hence the possibility of a
sex-linked inheritance as proposed by Bruning et al.
(1957). Subsequently, compiling the data for the Japanese
population, Niswander and Sujaku (1963) hypothesised
that an autosomal recessive gene with less penetrance in
females may lead to the formation of a supernumerary
tooth.
Finn (1967) proposed a female-limited X-linked auto-
somal dominant mode of transmission in his report of a
pedigree of 5 sibships over three generations in which all
14 females were affected, while the remaining three males
were unaffected. Furthermore, Cadenat et al. (1977) pos-
tulated that a recessive gene on an autosome and a gene on
the inhibiting X chromosome were responsible for the
formation of supernumerary teeth. Nevertheless, several
authors (Sedano and Gorlin 1969; Batra et al. 2005; Wang
et al. 2007) favoured an autosomal dominant mode of
inheritance with a lack of penetrance in some generations.
Several case reports have reported on the occurrence of
supernumerary teeth in siblings which are shown in
Table 1. Comprehensive lists of supernumerary teeth
reported in twins are presented in Tables 2 and 3; while
published reports on familial occurrence of supernumerary
teeth are given in Table 4. These reports clearly support the
notion that a genetic component is essential for the
development of supernumerary teeth.
Syndromes associated with supernumerary teeth
The bilateral occurrence of supernumerary teeth indicates
that mutant genes may be responsible for the formation of
supernumerary teeth (Messer 1972). Furthermore, the

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Table 4 Published case reports of supernumerary teeth occurring in families

References Country Ethnicity Family members Supernumerary teeth
Affected Mode of inheritance Arch Type Number

Hammond-Williams (1934) UK – Grandfather – Maxilla Mesiodens Double

Granddaughter Maxilla Mesiodens Single
Mason and Rule (1995) UK – Mother – Maxilla Mesiodens Single
– Son – Maxilla Mesiodens Double
Father Maxilla Mesiodens Single
Son Maxilla Mesiodens Single
Babu et al. (1998) India – Mother – Mandible – Multiple
Daughter Both Mesiodens, incisors Multiple
Sharma (2003) India – Father – Maxilla Mesiodens Single
Daughter Maxilla Mesiodens Single
Cassia et al. (2004) Lebanon – Cousins – Mandible Incisor Single
Male Mandible Incisor Single
Female Mandible Incisor Single
Female Mandible Incisor Single
Male
Batra et al. (2005) India – Father Autosomal dominant Both Premolars Multiple
Son Both Incisors, Premolars Multiple
Daughter Both Mesiodens, premolars Multiple
Orhan et al. (2006) Turkey Caucasian Mother – Both Premolars Multiple
Caucasian Son Mandible Premolars Multiple
Mother Both Premolars Multiple
Son Both Mesiodens, premolars Multiple
Wang et al. (2007) China Chinese Mother Autosomal dominant Both Premolars Multiple
Daughter Both Premolars, Distomolar Multiple
Krishnan et al. (2009) India Asian Father – Mandible Premolar Single
Daughter Mandible Premolars Double
Son Both Premolars Multiple
Acevedo et al. (2010) UK – Cousins – Mandible Premolar Single
Female Mandible Mesiodens Single
Male

occurrence of supernumerary teeth in patients with syn-
dromes such as cleidocranial dysplasia (CCD), Gardner’s
syndrome, and conditions such as cleft lip and palate fur-
ther emphasises the role of mutant genes in the develop-
ment of supernumerary teeth. The syndromes associated
with supernumerary teeth and their associated genetic loci
are displayed in Table 5.
Molecular mechanisms of supernumerary tooth
development
Most often, supernumerary teeth in mice occur in the
diastema area mesial to the first molars and represent the
rescued vestigial rudiments. During the early phase of tooth
development, the diastema is the site where several
transient vestigial dental buds develop. Although some of
these buds develop into the bud stage, they generally
regress and disappear by apoptosis, or in some instances
merge with the crown of the first molar (Peterkova et al.
2002, 2005, 2009; Prochazka et al. 2010; Viriot et al. 2002;
Witter et al. 2005). Tooth development is regulated by
major signalling pathways which also occur in the vestigial
tooth buds, the modulation of which can rescue the vesti-
gial tooth rudiments and lead to the formation of super-
numerary teeth (Tummers and Thesleff 2009).
Several mutant mouse strains which reportedly exhibit
supernumerary diastema teeth are presented in Table 6.
The features of supernumerary teeth reported in these
mutant strains and the corresponding human orthologs for
the mutant genes are also given (Table 6). Recently, Ahn
et al. (2010) reported that Sostdc1 serves as an inhibitor of

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Table 5 Syndromes associated with supernumerary teeth and their genetic locus
References Syndrome
Lee et al. (1997), Mundlos et al. (1997) Cleidocranial dysplasia
Groden et al. (1991) Gardner’s
Ferrante et al. (2001) Oro-facio-digital type I
Burdon et al. (2003) Nance-Horan
Momeni et al. (2000) Trichorhinophalangeal
Kitao et al. (1999) Rothmund–Thomson
Melamed et al. (1994) Ehlers-Danlos Type III
Cahuana et al. (2004) Ellis–Van Creveld
Regattieri and Parker (1973) Fabry disease
Himelhoch et al. (1987) Incontinentia pigmenti
OMIM = Online Mendelian Inheritance in ManÒ, NCBI database
Lrp5-and Lrp6-dependent Wnt signalling, thus repressing
the survival of the diastema or incisor vestigial tooth
rudiments. Therefore, inactivation of Sostdc1 elevates the
Wnt signalling and increases the proliferation and devel-
opment of vestigial tooth buds resulting in supernumerary
tooth formation. Furthermore, it has also been demon-
strated that Lrp4 can also inhibit canonical Wnt signalling
by binding to Sostdc1 and resulting in functional loss of
Lrp4 which may subsequently lead to elevated Wnt sig-
nalling. In addition, Apc loss-of-function or b-catenin gain-
of-function mice and Sp6 (Epiprofin) deficient mice can
develop rudimentary supernumerary teeth which arise
directly from the primary tooth germs or dental lamina.
Although mice have a highly reduced primary dentition,
with one incisor and three molars separated by a diastema,
which is toothless, mouse models are frequently used to
study the molecular mechanisms involved in tooth devel-
opment. Mice teeth are not replaced hence mouse models
may not be wholly appropriate for studying supernumerary
tooth formation (Huysseune and Thesleff 2004). Never-
theless, mouse models have increased our understanding of
the complex molecular mechanisms involved in tooth
development. Animals that replace their teeth throughout
life such as, reptiles, lizards, fish, and snakes, as well as
mammals such as ferrets (Berkovitz and Moore 1975;
Fraser et al. 2004, 2006a, b; Jarvinen et al. 2009; Handri-
gan and Richman 2010; Handrigan et al. 2010) are cur-
rently used to analyse successional tooth formation.
Information obtained from these alternative models
indicates that successional teeth are initiated from the
epithelium of the dental lamina that develops from the
lingual side of the primary tooth enamel organ, subse-
quently elongates and buds into the jaw mesenchyme to
form the successional tooth. Therefore, maintenance or
reactivation of a competent dental lamina is essential for
the development of supernumerary teeth. In this regard,
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Eur Arch Paediatr Dent (2013) 14:279–288
OMIM Gene Locus
119600 Runt related transcription factor 2 (RUNX2) 6p21
175100 Adenomatous polyposis coli (APC) 5q21-22
311200 Orofacialdigital syndrome 1(OFD1) Xp22.3-p22.2
302350 Nance Horan syndrome (NHS) Xp22-13
190350 Trichorhinophalangeal syndrome 1 (TRPS1) 8q24.12
268400 RecQ protein-like 4 (RECQL4) 8q24.3
130020 Collage type III (COL3A1) 2q32.2
225500 Ellis–Van Creveld (EVC) 4p16.2
301500 Alpha-galactosidase A (GLA) Xq22.1
308300 Inhibitor of kappa light polypeptide Xq28
gene enhancer in B cells, kinase of,
gamma (IKBKG/NEMO)
Sostdc1 is essential to define the identity of the dental
lamina as it is expressed in the elongating successional
dental lamina at the interface between the lamina and the
primary tooth, as well as the buccal side of the dental
lamina (Jarvinen et al. 2009). Furthermore, Wnt signalling
which regulates the fate of dental epithelial stem cells that
are responsible for the formation of successional dental
lamina is essential if supernumerary teeth are to develop
(Handrigan et al. 2010).
Current knowledge in the molecular mechanisms
responsible for tooth development indicates that different
pathways encompassing several genes and transcription
factors are essential for the development of supernumerary
teeth.
Discussion
The proposed hypotheses and the recent molecular research,
using various animal models to obtain new insights into the
development of supernumerary teeth, have to date been
unable to identify the aetiology of supernumerary teeth. No
studies have been able to distinguish between different
aetiologies for the different locations of supernumerary
teeth, while, from a developmental or molecular perspective,
the proposed hypotheses may be plausible and explain the
origin of different types of supernumerary teeth. The only
clearly evident feature, based on the existing published
reports, is that it is logical to state that supernumerary teeth
have a genetic component in their aetiology.
To date, no clear genotype–phenotype correlation has
been established in patients with syndromes that are known
to be associated with supernumerary teeth (Otto et al.
2002). For example, individuals with CCD who have
identical mutations on the RUNX2 gene exhibit wide var-
iation in the number of supernumerary teeth. Furthermore,
Eur Arch Paediatr Dent (2013) 14:279–288
Table 6 The reported mouse
References
mutants associated with
supernumerary teeth and their Ohazama et al. (2009)
corresponding human orthologs
Seppala et al. (2007)
Zhang et al. (2003)
Ohazama et al. (2009)
Ohazama et al. (2009)
Klein et al. (2006)
Peterkova et al. (2009)
Klein et al. (2006)
Yanagita et al. (2006)
Murashima-Suginami et al. (2008)
Ohazama et al. (2008)
Munne et al. (2009)
Ohazama et al. (2008)
Zhang et al. (2009)
Nakamura et al. (2008)
Kuraguchi et al. (2006)
Wang et al. (2009)
Jarvinen et al. (2006)
Liu et al. (2008)
Zhou et al. (1995)
Kaufman et al. (1995)
Mustonen et al. (2003)
Kangas et al. (2004)
Tucker et al. (2004)
Gruneberg (1966)
Sofaer (1969)
Peterkova et al. (2005)
Danforth (1958)
the asymmetrical occurrence in the maxilla and mandible
implies that the number and position of supernumerary
teeth may not solely be governed by RUNX2 mutation.
Therefore, non-genetic factors, such as epigenetic factors,
modifier genes, copy number variations, as well as envi-
ronmental factors, may also be involved in the formation of
supernumerary teeth in CCD (Suda et al. 2007, 2010; Ryoo
et al. 2010).
In an attempt to obtain greater knowledge about the
aetiology of supernumerary teeth, innovative multifaceted
approaches involving both animal and human genetic
studies are essential. Although recent research has
enhanced our understanding of the molecular mechanisms
involved in tooth morphogenesis and differentiation, rela-
tively little is clear about tooth initiation, genes that control
the development of successional teeth, and mechanisms
fundamental for supernumerary tooth formation. Never-
theless, several mouse mutant genes have been identified to
285
Mouse mutants Human orthologs
Gas1 Growth arrest specific 1
Gas1; Shh Growth arrest specific 1; sonic
hedgehog
Tg737orpk hypomorph Intra-flagellar transport 88
Wnt1 Wingless-type MMTV integration
site family, member 1
Spry2 Sprouty 2
Spry4 Sprouty 4
Ectodin (Sostdc1, USAG1, Sclerostin domain containing 1
Wise)
Lrp4 (Megf7) Low density lipoprotein
hypomorph receptor-related protein 4
Osr2 Odd-skipped related 2
Epiprofin Sp6 transcription factor
K14-Cre; Apc Adenomatous polyposis coli
K14-Cre; Apc
K14-Cre; b-catenin Catenin, beta interacting protein 1
K14-Cre; Ctnnb1 Lymphoid enhancer-binding factor 1
K14-Lef1
Pax6Sey Paired box 6
K14-Eda Ectodysplasin A
K14-Edar Ectodysplasin A-receptor
Tabby –
Eda Ectodysplasin A
Di –
be associated with supernumerary tooth formation. The
human orthologs of these mouse mutant genes could form
the basis for the selection of candidate genes that neces-
sitate evaluation in humans.
The availability of families and individuals with non-
syndromic forms of supernumerary teeth is a valuable
resource for the identification of genes and mutations that
lead to the development of this condition. Although, a
genome wide scan (GWA) would ascertain the potential
genes responsible for the formation of supernumerary
teeth, it is difficult to recruit a sizeable sample to obtain
valid results. Furthermore, the cost implications associated
with this approach would render its use non-affordable.
Therefore, a logical approach would be to ascertain the role
of human orthologs of mouse mutant genes using a case–
control association study in humans.
Recently, with the implementation of stringent guide-
lines for the use of radiographs in children (Isaacson et al.
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2008), it is now impossible to expose all children to ion-
ising radiation in an attempt to simply identify supernu-
merary teeth in the relatively small number of individuals
in whom they occur. Therefore, identification of genetic
risk factors responsible for the formation of supernumerary
teeth would be essential in an attempt to develop a
screening tool to determine the genetic risk of an individual
using a non-invasive method for collecting human DNA.
Eventually, a better understanding of the molecular
genetics of supernumerary teeth in humans can be utilised
to facilitate tooth regeneration and replacement tooth forms
in the dental clinic.
Conclusion
Despite the proposal of several hypotheses, the aetiology of
supernumerary teeth still remains unclear. Each of the
proposed hypotheses is plausible and explains the origin of
different types of supernumerary teeth. Nevertheless, it is
apparent that different pathways encompassing several
genes and transcription factors are essential for the devel-
opment of supernumerary teeth.
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