Teeth:

Common
Concerns

rarechromo.org
Teeth: common concerns

Index
How do teeth develop? page 3
Teething page 4
Early teething page 4-
4-5
Early adult teeth page 5-
5-6
Late teething page 6-
6-7
Unusual sequence page 7
Missing teeth page 8-
8-10
Extra teeth page 10-
10-11
Widely spaced teeth page 11-
11-12
First teeth don’t fall out page 12
First teeth fall out early page 13
Cleft lip and/or palate page 13-
13-14
Malocclusion Incorrect alignment between jaws page 14-
14-16
Crooked teeth page 16-
16-17
Teeth in the wrong place page 17
Crowded teeth page 17-
17-18
Small teeth page 18-
18-19
Large teeth page 19
Taurodont teeth page 19
Unusually shaped teeth page 20-
20-21
Double teeth page 20
Poor enamel and dentine page 21-
21-22
Some genes page 23-
23-24
Some syndromes page 24-
24-25
References page 26
Resources page 26

Unique publishes a separate guide: Looking after your child’s teeth

Unique acknowledges that this guide cannot be comprehensive. We welcome

new information on the impact of rare chromosome disorders on teeth. Please
email Unique at info@rarechromo.org or Prisca Middlemiss @ prisca@rarechromo.org

2
What are teeth made of?
Teeth are made of three layers of hard material found nowhere else in the body.
Enamel is the hard covering.
Dentine is the slightly elastic tissue that forms most of the tooth. In the US, it’s
dentin.
Pulp is the material beneath the dentine where the blood vessels and nerves
are.
Cementum is a thin layer of hard tissue covering the root.
Cusps and fissures are pointed projections and grooves on the biting surface.

How do teeth develop?

The development of teeth and the face is controlled by many different genes.
Acting together in a very complex way, genes programme the pattern of the
teeth in the top and bottom jaws, their shape, and the way they develop. Anything
that disrupts the smooth functioning of these genes can cause a dental problem.
So dental problems are very common – both among people without
chromosome disorders and people with them. In children with chromosome
disorders, there is quite often more than one dental problem.

Chromosome
What are genes?
Genes are the basic units of heredity. They act as
instructions to make molecules called proteins.
Humans have about 20,000 genes in their
Cell chromosomes.

Gene

DNA

Words
Dentists sometimes use technical words. Sometimes other words mean the
same thing.
First teeth Baby teeth Milk teeth Primary teeth Temporary teeth
Deciduous
Adult teeth Permanent teeth Big teeth Secondary teeth Second teeth
Erupt Appear Emerge Break through Come through
Fall out Lose Shed Exfoliate
Front tooth Incisor Incisors can be central (middle) or lateral (side)
Back tooth Molar
Wisdom tooth Third molar
Top Maxillary Upper
Bottom Mandibular Lower
Contralateral The tooth in the same position on the other side of the mouth
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Teething
A baby’s first teeth start to form at around week 6 in pregnancy.
Around 4 months into pregnancy the first teeth start to absorb calcium.
Adult teeth start to form during pregnancy, at around week 20.
The adult teeth start to absorb calcium when a baby is around 4 months old.
Teeth usually appear in the same order and around the same age. Generally,
bottom teeth come through before top teeth, and girls’ teeth come through
earlier than boys’.
We usually have 20 first teeth. First teeth usually start to appear between 4-6
months and one year. The last of the first teeth to come through are usually the
back (second) molars, which generally appear by 2½ to 3 years, although it can
be later.
A ‘typical’ teething
chart. In children
with chromosome
disorders, teeth can
come through early
or late, and in an
unusual order.
There is quite often
more than one
dental problem.

We usually have 32 adult teeth. Adult teeth usually come through between 6-7
years (bottom front teeth) and 13 years (back molars). Third molars (wisdom
teeth) usually come through between 17-21 years, if they appear at all.
In children with chromosome disorders, teeth can erupt in a different order.
Pain pathways are late to develop in some children with a chromosome
disorder, so they may show no discomfort when teething.

Early teething
Some babies are born with visible teeth, or they come through in
the first month. They usually have very shallow roots or no roots
at all. If the tooth is loose or gets in the way of feeding, it needs
to be removed to prevent a baby swallowing it. Natal and
neonatal teeth are usually a baby’s normal first teeth.

Words Natal teeth

Natal teeth Teeth visible at birth
Neonatal teeth Teeth that come through in the first month
of life
Pre-
Pre-erupted teeth Teeth that appear within months 2 and 3
4
Any baby can have natal or neonatal teeth. They are found in around 1 baby in
every 2-3,000. We don’t know if they are more common in babies with a
chromosome disorder. Within Unique, babies with the following disorders have
been reported with one or more natal or neonatal teeth: 1q24 duplication; 1p36.3
deletion; 1q43 deletion; large interstitial deletion of 7p; 6q27 duplication; large
interstitial deletion starting at 8q11.21; inverted duplication with deletion of 8p;
9q34.3 deletion (Kleefstra syndrome); 10q25q26 deletion; marker chromosome 15;
16p13p12 duplication; 22q13.31 deletion (Phelan-McDermid syndrome);
unbalanced translocation between Xp and 3q12.
It’s more common for teeth to appear from 2 months onwards. Most often, one or
both of the bottom front teeth erupt early. Their development is usually correct for
the age of the baby, so the enamel is not yet completely formed. This may be
because the tooth has developed very superficially under the gum rather than
within the jaw bone.
Early first teeth do not in themselves pose a problem, but parents need to bring
forward their baby’s first visit to the dentist. Sometimes just one or two teeth
erupt early, but within Unique it is more common for a baby to get all their first
teeth early. At Unique it is not unusual for a baby to have all their first teeth before
their first birthday. The teeth may look perfectly normal, or they may have an odd
shape, or be unusually small or large. Sometimes the enamel surface of the tooth
is thin, chalky or pitted.
When the first teeth come through early, they may fall out early, and the adult
teeth may also come through early, but this does not always happen.
Within Unique, babies with the following disorders have had early teething:
2-3 months (prematurely erupted teeth)
8p23 deletion; trisomy 8 mosaicism; 15q deletion; 15q duplication; 22q13.3
deletion (Phelan-McDermid syndrome).
4-5 months
16p12 deletion; 10p deletion with Yq duplication.
Not specified
2p15p16.1 deletion; 2p16.3 deletion; 2p24 deletion; 3q21 duplication; 3q29
duplication; 4q35.1 deletion; 4; 8 translocation; 5q32 deletion; 6q15 deletion; 6q24
duplication; trisomy 8 mosaicism; 16p12 deletion; 17p11.2 duplication (Potocki-
Lupski syndrome); 22q13.3 deletion (Phelan-McDermid syndrome); 45X/46XY.

Early adult teeth

Adult teeth that come through early can follow early loss of first teeth. Children
with hormone disorders such as too much growth hormone or too much thyroid
hormone (hyperthyroidism) can get their adult teeth early.
Among Unique members, adult teeth can start coming through from 4 years.
Within Unique, children with the following disorders have had early adult teeth:
1q21.1 deletion; 3q13 deletion; 4p duplication; 6p25 deletion; 9p22 deletion; 10q26
deletion; recombinant 15.
5
One family’s experience
“Her first tooth erupted when she was 6 weeks old,
and she had all her first teeth through by 10 months.
She then lost her first teeth from about the age of 4
over a normal period of time, but her second teeth
didn't start to come through for about 9 months after
losing her first front teeth.”
First adult tooth coming
Adult teeth: ‘typical’ sequence
through slightly early at
5½ years

All adult teeth by 10

Late teething years
It is perfectly normal for first teeth to come through
between 6 and 12 months. It’s known that children with low thyroid levels,
children with hypopituitarism (low levels of one or more of the 8 hormones
produced by the pituitary gland), and children with Down’s syndrome have teeth
that come through late. It is Unique’s experience that teeth come through late in
children with other chromosome disorders. Four times as many families tell us
that their child’s teeth came through late as came through early. In most late-
teething children, first teeth were seen between 12 and 18 months, and most
often between 12 and 15 months. Very occasionally, first teeth erupted after the
age of 2, and these are noted in the disorder list that follows. In many cases but
certainly not all, late teething was not the only dental issue: unusual sequence;
missing teeth; crowding; crooked teeth and abnormally shaped teeth were some
of the other dental concerns.
There is nothing that you can do to stimulate teeth to come through early, and
there can be advantages: if you are breast feeding, you are less likely to be
painfully bitten. However, a baby or toddler without teeth is less likely to chew
well. Even if your chid has no teeth, they should still see a dentist by their first
birthday. If your baby has no teeth by 18 months, you should certainly see a
dentist, who may refer your child for a specialist opinion.

6
Unique has records of late teethers with these diagnoses, starting with the most
common: an extra X chromosome, especially 48,XXXX (tetrasomy X) and
49,XXXXY; 15q26 deletions; 1q32q42 duplication; 4q12q21 deletion (in one child, 2
years); 9p duplications; 10q26 deletions; Pallister-Killian syndrome; 19p13.13
microdeletion syndrome; 2q37 deletion; 1q21.1 microdeletion; 1q24 deletion;
2q24 deletion; 2q11q21 duplication; ring 2; 3p25 deletion; 3q27q29 deletion; 44p
duplication; q21 deletion; 4q28 deletion; 4q25q31 duplication; 5p15.3 deletion;
5q14.3q15 deletion; 5q15q22 deletion; 6p25p24 duplication; 6q14q15 duplication;
6q25.3 duplication; 7q11.22 microdeletion; 7q31q32 deletion; 7q36.2 deletion;
7q11.23 duplication; 7q36.1 duplication; 8p12 interstitial deletion; 8p23
duplication; 9q22q31 deletion; 9q32q34.1 deletion; Kleefstra syndrome (9q34.3
deletion); ring 9; 10q23.2 deletion; 11p15.4 deletion; 12q14.3q14 deletion; 13q12
interstitial deletion; 14q13q21 deletion; 15q24.1q24.2 deletion; idic 15; 16p13.11
microdeletion; 16p11.2 microduplication; 17p13.3 deletion; Koolen-de Vries
syndrome (17q21.31 deletion); 19q13.4 microdeletion; 22q11.2 deletion; Emanuel
syndrome (partial trisomy 22); Xp11.23p11.22 duplication; an extra Y
chromosome. In addition, late teething was seen in children with a variety of
dual imbalances, usually involving a loss of DNA from one chromosome and
extra DNA on another. The X chromosome was involved in 38 per cent of these
cases. In one child with loss of DNA from Xp22.3, first teeth erupted at 2 years.
It is more unusual for families to tell Unique that adult teeth erupted late.
Families with these disorders have had that experience: 1p31p22 deletion;
7q22q31 deletion. However, many families say that their child’s first teeth are
delayed in falling out. When the first teeth are late to fall out, the adult teeth are
often late to erupt.

Unusual sequence
In typically developing babies the teeth erupt in a well known order, very roughly
starting at the bottom and working from the middle to the back. This order is
disrupted in some babies with chromosome disorders. Unique records show
that when tooth sequence is disrupted it is very common to have other dental
concerns as well, especially late teething and missing teeth.
There is nothing that you as a parent can do to change this, but it can help to be
aware that back teeth can come through while front teeth are still missing.
Some babies are upset while their back teeth are coming through, and need to
bite or gnaw to help their discomfort.
Unique’s records show that teeth erupted in an unusual sequence in babies with
these chromosome disorders: 2q33.1 deletion; 3q26.33 deletion; 3q29 deletion;
5q13.33 duplication; 6q25.3 duplication; 8q23.1 interstitial duplication;
9q33.3q34.11 deletion; an extra ring chromosome 9; 10q26 deletion; 12p
duplication; 15q26 deletion; 22q11.2 deletion; Phelan-McDermid syndrome
(22q13.3 deletion).

7
Missing teeth
Words
Missing teeth Hypodontia This is severe if more
than 6 teeth are missing, excluding wisdom
teeth (3rd molars)
Oligodontia More than 6 teeth missing, excluding
wisdom teeth (3rd molars)
Anodontia Total failure of first or adult teeth to
develop No teeth at all
Tooth that doesn’t come through Unerupted There is a close link between
tooth missing teeth, very small
Resorption Dissolving of part of the tooth within teeth and unusually formed
the bone – usually the root. teeth, especially cone-shaped
Tooth erupts but then gets submerged in the teeth.
gum Infraocclusion Submerged Ankylosed
When a tooth does not appear, you won’t know at first why: is it in the jawbone
but invisible, or is it really missing? A dental X-ray will give the answer, if this is
possible and justifiable. If an X-ray shows an embryonic tooth, but a tooth does
not come through, it may be because it is in the wrong position or there is not
enough room in the jaw. The developing tooth becomes impacted. It may be
possible with surgery to free enough space for the tooth to come through. If it is
not possible to remove other teeth to allow the impacted tooth through, it will
often stay within the jaws without causing problems, but may damage or resorb
the roots of neighbouring teeth.
Sometimes a tooth erupts, but then gets submerged in the gum. This is most
common in children who take particular medicines to control their epilepsy: one
of the effects of some anti epilepsy drugs is to make the gums enlarge [see
Looking after your child’s teeth Medicines ].
Having some missing adult teeth is not as unusual as you may think. Between
one person in 12 and 1 in 30 has one or more missing adult teeth. If you include
wisdom teeth (third molars), it’s even more common: more than 1 person in 5
has missing wisdom teeth. But missing teeth are probably more common in
people with chromosome disorders. The teeth that usually fail to appear are the
bottom second premolars and the top lateral incisors [see Diagram, page 5].
When just one top lateral incisor is missing, the other can be peg-shaped or
conical.
It’s not so common to be missing 6 or more teeth (severe hypodontia). This
affects about 1 person in 400. Having no teeth at all (anodontia) is really very
rare, and we have not seen this at Unique.
Missing first teeth is less common. Less than 1 baby in 100 is missing any of the
20 first teeth. You’ll know by 3-4 years old if the tooth is really missing. Usually if
the baby tooth is missing, the adult tooth will also be missing.

8
Missing teeth is linked with many syndromes, including chromosome disorders.
Sometimes there is a pattern to the missing teeth. Opposite pairs of teeth, or
groups of teeth are missing. More often it’s haphazard.
The cause of missing teeth is usually genetic, although the environment can
have an influence. How common it is varies around the world, and it is more
common among females than males.
There is a close link between missing teeth, very small teeth and unusually
formed teeth, especially cone-shaped teeth – all can be caused by disruption in
the same genes. Among those with an extra X chromosome, some of the other
teeth may be very large.
Among children with chromosome disorders the impact of missing teeth on
feeding and chewing needs to be assessed in the context of any low muscle tone
in the face and mouth, and any impact on speech and language development.
Gaps caused by missing adult teeth can be filled either by using braces to
reposition teeth, by transplanting a tooth from an overcrowded part of the
mouth, or by using a dental implant, or even false teeth. Among children with
chromosome disorders, the benefits
are balanced against any stress the
child feels about dental visits, and their
ability to cope with interventions in
their mouth.
Spaces in the smile can be disguised by
a variety of techniques, but is often best
planned by a specialist dental team
rather than a family dentist. It should
be remembered that although the teeth
happen to be in the middle of a smile,
we smile with our whole face, eyes
included. Perfect teeth are not
essential for a lovely smile. Total
anodontia can be very difficult to
manage, particularly if there is any
developmental delay which makes
A lovely smile coping with full dentures difficult.
Unique’s records show that missing
teeth were especially common among young men and women with extra X
chromosomes, and to a lesser extent among young men with extra Y
chromosomes. Those with 48,XXYY were most likely to report missing teeth.
Missing teeth were also seen repeatedly in people with Koolen-de Vries
syndrome and 1q32q42 duplications, 2q37 deletions, 3q27 deletions, 4p
duplications and 7q11.22 deletions (one top front tooth). Missing teeth were also
seen in people with these disorders: 1q4243 deletion; 1q44 deletion; 2q12
interstitial duplication; 3p25 deletion; Wolf-Hirschhorn syndrome (8 teeth
9
missing); 4q31 deletion; 4p15.1 duplication; 6p25p22 duplication; 7q34 deletion;
7q36 deletion; 8p21 deletion; trisomy 8 mosaicism; Alfi’s syndrome (9p22
deletion); Kleefstra syndrome (9q34 deletion); trisomy 9p; 13q32q34 deletion;
14q11.2q13.1 duplication; 15q13.2q13.2 deletion; 15q26.1 deletion; 15q13q21
duplication; idic 15; 16p11.2 microdeletion; 16q11.2q12 deletion; 17p13.3
deletion; 17p12 duplication; 17p13.1 microduplication; 18p deletion. In addition,
missing teeth were seen in children with a variety of dual imbalances involving a
loss of DNA from one chromosome and extra DNA on another: chromosomes 4
and 8; 5 and 9; and 13 and 18 were involved.

Extra teeth
Words
Extra teeth Supernumerary teeth Supplemental teeth Hyperdontia Many extra
teeth
Mesiodens Extra top front tooth
Paramolar Extra top molar usually on the cheek side of the gum, rather than
the mouth side
It’s not uncommon to have an extra tooth. At least
1 to 3 people in every 100 have an extra adult tooth.
An extra first tooth is not so common. Extra adult
teeth are more common in men than women. Extra
teeth are more common in people with a cleft
palate. Generally speaking, more than 90 per cent
of extra teeth are in the upper jaw, and most
commonly in the midline of the upper jaw.
A small extra tooth in the
Extra teeth can be shaped like the teeth they are
middle of the top jaw
next to, but usually have an abnormal shape.
Sometimes they erupt fused with the neighbouring tooth.
The cause of extra teeth is still not understood. Genes are known to play an
important role. Among other theories, one is that when the tooth bud forms at 6
weeks of pregnancy, it splits in two, creating two teeth; another is that extra
teeth are evolutionary throw-backs, revealing teeth that were seen in our
ancestors but have disappeared in modern man.
Sometimes the extra teeth are found in the jaws when your child has a dental X-
ray. Usually they are first noticed when they erupt as an unusually-shaped tooth,
or when their presence delays the eruption of an adult tooth. If an upper central
incisor fails to erupt within 6 months of its partner, X-ray investigation is
recommended. Depending on the position, and the effect the extra teeth have on
the other teeth, they may require extraction or be left alone.
Unique’s records show that extra teeth were especially common among young
men and women with trisomy 8 mosaicism and other duplications of the short
arm of chromosome 8; in people with 7q33 deletion (or duplication); and in
people with 15q26 deletion. They were also found in people with 1q42.2

10
duplication; 2p15p16.1 deletion; 3q duplication; 4p duplication; 4q27q31 deletion;
6q27 duplication; 7q11q21 duplication; 9p deletion; trisomy 9 mosaicism;
10q25q26 duplication; 15q11.2 microdeletion; 16p proximal deletion; 22q11.2
duplication; and dual imbalances involving a loss of DNA from one chromosome
and extra DNA on another: chromosomes 4 and 8; 4 and 10; 8 and 15; and 19 and
22 were involved.

Widely spaced teeth

Word
Diastema Gap between the top front teeth
Gaps between teeth are common, especially if
your child has small teeth in a normal-sized jaw.
If there is poor lip muscle tone or an unusual
tongue-thrust on swallowing, the gaps may be
due to the front teeth being splayed outwards. It
may be possible to close spaced front teeth with
orthodontic treatment, but many specialist
orthodontists would prefer to leave mildly
spaced teeth, as they are easier to brush than
crowded or rotated teeth.
Unique’s records show that widely spaced teeth
were especially common among young men and
women with Kleefstra syndrome (9q34
deletions); Koolen-de Vries syndrome (17q21.31
deletions); 21q22 deletions; and 1q21.1
microduplications. They also occurred in people
with 1p36 deletion; 2q24.2 deletion; 2q37.3
deletion; 2q31q35 duplication; 3q27 deletion;
4p16p15 duplication; 5p15 duplication; 5q15q22 deletion; 7q11.22 deletio;
7q11.23 duplication; 7q22q31 deletion; 7q31q34 duplication; 7q32 deletion;
inverted duplication with deletion of 8p; 9p22 deletion; ring 9; trisomy 9p; 10q26
deletion; 11q23 triplication; inverted duplication
of 12p; 16p terminal deletion; 16q22q24 deletion;
17p13 duplication; duplication of Xp11.23;
duplication of Xq28; an extra Y chromosome; and
dual imbalances involving a loss of DNA from
one chromosome and extra DNA on another:
chromosomes 2 and 9; 4 and 8; 8 and 12; X and
16 were involved.
A midline diastema is common whether you have
a chromosome condition or not, and either self
corrects in time, or can be improved if this is
considered necessary. Among Unique families it

11
has been recorded in young men and women with 1q21.1 microdeletion; 2p16.3
deletion; 4q21 deletion; 6q13q16 deletion; idic 15; 16p terminal deletion;
tetrasomy X; and dual imbalances involving
extra DNA on chromosomes 6q24.1 and
Xp22.31.

First teeth don’t fall out

One of the most common dental concerns
faced by Unique families is the failure of one or
more first teeth to fall out. Young adults
frequently still have some first teeth in place.
First teeth usually fall out when the adult tooth First teeth still present
dissolves its root from beneath, causing the
first tooth to become mobile and eventually
exfoliate. If this process is delayed, the tooth
will not fall out, delaying or deflecting the
eruption of the adult teeth. Sometimes the
adult teeth erupt in front or behind the first
teeth so the child appears to have two sets. If
no adult teeth have erupted by the expected
Retained lower baby incisors,
age, the dentist can X-ray the jaws to see
giving the appearance of a
whether they are present but unerupted. They
double row of teeth, and
may then recommend removing the retained
causing severe crowding
first teeth – either with local anaesthetic
injections or under a general anaesthetic in hospital.
Unique’s records show that first teeth that failed to fall out were especially
common among young men and women with extra DNA on chromosome 8
(trisomy 8 mosaicism, supernumerary chromosome 8, inverted duplication with
deletion of chromosome 8); duplications of 9p (isochromosome 9p and trisomy
9p) and Kleefstra syndrome (9q34.3 deletion).
They also occurred in people with 1q41 deletion; 2p16.1p15 deletion; 2q23
deletion; 2q24 deletion; 2q33 deletion; ring 2; 2p13p21 duplication; 2q37.3
duplication; 3p21p14 deletion; 3p25 deletion; 3q26q27 deletion; 3q26 terminal
deletion; 5p15 deletion; 5q Interstitial deletion; 5q35 duplication; an extra small
chromosome 5; 5p15 duplication; 6p25 deletion; 6q16q22 deletion; 6q25q26
deletion; 6q24q26 duplication; 7q22 deletion; 7q31q33 deletion; 10p duplication;
10q23 deletion; 10q25 deletion; 10q26 deletion; 10q11q22 duplication; 12p
terminal duplication; 12p13 deletion; 15q26 terminal deletion; idic 15; 15q13q21
duplication; 16p12 deletion; 16p duplication; 18p11 deletion; 18q deletion
syndrome; 19q13 microdeletion; 21q11q22 deletion; 22q13 deletion (Phelan-
McDermid syndrome); Emanuel syndrome; one or more extra Y chromosomes;
duplication of Yq; 48, XXYY; 49,XXXXY; and dual imbalances involving a loss of
DNA from one chromosome and extra DNA on another: chromosomes1 and 5; 3
and 8; 4 and 14; 10 and 22; and X and 11 were involved.
12
First teeth fall out early
Early exfoliation of first teeth is rare among Unique children and does not
typically cause any problems. When the tooth comes out, your child may swallow
it, but this does not cause any problems. Unique’s records show that children
with the following disorders started to shed their first teeth before the typical
age of 6 years: 1q42q43 deletion; 3q13q21 deletion; 4p16p15 duplication; 6q14
duplication; 22q13 deletion (Phelan-McDermid syndrome); 10q deletion with Yp
duplication.

Cleft lip and/or palate

During early pregnancy different parts of the face develop separately and then
join together. When some parts do not join properly, the result can be a cleft. A
split in either the upper lip, the roof of the mouth or both is one of the most
common birth anomalies, and can occur in association with more than 300
different syndromes, as well as chromosome disorders that are not part of a
syndrome. At least 20 genes are known to be associated with clefts, and there
may be more.
Many tooth disorders can occur with a
cleft palate and/ or lip. The more
severe the cleft, the more teeth are
likely to be affected. At the front of the
top jaw, there can be missing teeth,
extra teeth, the teeth may be too big or
too small; or there may be gaps. Gaps
may occur between the canine (eye
tooth) and the lateral incisor.
Sometimes the incisor is missing
altogether. Or there may be 2 lateral
A repaired cleft palate
incisors, one on each side of the cleft.
Occasionally the middle front teeth
may be affected in the same way as the
lateral incisor. Teeth in the area of the cleft may be displaced, so they come
through in unexpected positions. Teeth may erupt very late or early. If teeth are
missing, most commonly it’s the upper lateral incisors. The teeth may be
impacted (blocked) and not come through by themselves. An extra lateral incisor
in first teeth is very common in toddlers with a cleft.
Some disorders that are known to disrupt the middle of the face, such as 18p
deletions, can also have effects such as malocclusion (see below), leaving a gap
between top and bottom teeth at the front.
Sometimes the enamel of the teeth in the cleft area is not properly formed, and
those teeth may be prone to decay. The shape of the tooth in the cleft area may
be different. Adult teeth may have more irregularities. Both the crown and the
root of the incisor or other teeth may be irregularly shaped.

13
The palate is often narrow and the teeth are relatively large and crowded, so it’s
hard to keep them clean, and free of decay, and for the dentist to get access.
Children with a cleft need the same dental care as other children but they also
need early evaluation by a dentist familiar with clefts. This is usually arranged
through a cleft team or craniofacial treatment centre. Orthodontic evaluation
can be before the child has any teeth, to assess facial growth, especially the
growth of the jaws. If any surgery is needed, dental and other surgery is usually
scheduled to coincide so the child has no more surgical operations than
necessary.
Unique’s records show that midline dental problems were especially common
among young men and women with an 18p deletion (single front tooth). They
also occurred in people with a 2q duplication; 3q27 duplication; 4p duplication;
9q21 microdeletion; duplication 17p12; 18q22 deletion; and a 7; 12 unbalanced
translocation.

Malocclusion Incorrect alignment between jaws

Words
Malocclusion Abnormal bite
Overjet Protruding upper teeth
Overbite Teeth overlap too much
Crossbite Reversed bite
Scissor bite Molar teeth miss each other completely when biting
In an ideal world the teeth of the upper jaw would fit
perfectly with the teeth of the bottom jaw when the
mouth is closed. Dentists call this perfect occlusion.
Very few people have perfect occlusion, but most
occlusion abnormalities are so minor that they don’t
need treatment. Any obvious variation from the perfect
fit is called malocclusion, and this includes significant
overbite, open bite and crossbite. A significant
malocclusion may cause problems with chewing, but
rarely affects speech. Very marked malocclusion can Increased overjet,
mean that a child cannot chew at all. Sometimes the seen from the side
degree of mismatch is not clear until the child goes into
puberty and their face takes on its adult shape.
Overjet means there is a horizontal discrepancy
between the teeth. This may be due to habit e.g. thumb
sucking or may be due to a skeletal abnormality such as
retrognathia where the bottom jaw is too small.
If the problem is due to a small-sized lower jaw it is
Crossbite: top tooth
termed retrognathia, such as occurs in the Pierre Robin
trapped behind bottom
sequence. When the lower jaw is too short, the upper
tooth
incisor teeth can appear to protrude, and may not be
covered by the lips at rest.
14
A crossbite of the front teeth is when one or more of the upper incisors are
trapped behind the lower incisors. If severe, this can cause damage to the teeth
or supporting gum tissue. A crossbite of the molar teeth at the back of the
mouth may be because the top jaw is too narrow. This sometimes is a result of
persistent mouth-breathing, particularly if the back of the nasal passages are
chronically blocked by large adenoids.
An open bite is where the teeth do not meet,
usually at the front, and can have several
causes. Careful assessment of lip muscle
function and tone should be made, including
what happens with the lips and tongue during
swallowing. Discussion with a specialist speech
and language therapist will be helpful. A
persistent “tongue thrust” swallowing pattern
can also cause an open bite. Sometimes the
shape of the jaws will make it impossible for the
teeth to meet, and this is called a “skeletal open
bite”.
Treatment depends on your child, how far apart
the teeth are, how much treatment your child Open bite:
can tolerate, whether the mismatch is expected the teeth do not meet.
to get worse, and your opinions and wishes. The
gentlest treatment is the use of removable braces (commonly but incorrectly
termed ‘retainers’), but these are only able to correct the mildest malocclusion.
Modern orthodontic treatment usually involves fixed braces (‘train-track’
braces) which are provided by specialist orthodontists. It is very difficult to find
an orthodontist brave enough to offer fixed-appliance treatment for a child with
challenging behaviour, and this is understandable in view of the co-operation,
motivation and multiple visits involved. Referral to hospital-based orthodontic
services may be the most successful route to treatment if it is possible.
Tooth extractions, surgical exposure or removal of unerupted teeth, bonding
chains or even corrective jaw surgery are all features of advanced treatment of a
malocclusion. The more invasive the treatment options, the more the need or
desire for treatment should be examined.
Treatment can sometimes start early, then rest for observation and monitoring,
followed by more treatment when the adult teeth erupt.
Unique’s records show that overbite was especially common among boys with
an extra X chromosome, and among boys and girls with a 5p15 duplication,
7q22q31 deletion; a 12q14 deletion, or a 17p11.2 duplication. Overbite also
occurred in people with a 1q41 deletion; ring 1; 2q11.2 deletion; 3q terminal
deletion; 3q26 terminal duplication; 4p duplication; 4q25q28 deletion; 4q31
terminal deletion; 4q32q34 deletion; 4p16p15 duplication; 5p15 duplication; 8p23
deletion; trisomy 8 mosaicism; 9q32q34 duplication; ring 10; 11q23 triplication;
15
ring 13; 15q13 deletion; 15q24 deletion; 15q25 deletion; 15q26 deletion;
15q11q14 duplication; idic 15; 16p13.3 duplication; 17p13.3 deletion; Koolen-
deVries syndrome (17q21.31 deletion); 17p11.2 duplication; a 20p12
microdeletion; ring 21; 22q11.2 deletion; Phelan-McDermid syndrome (22q13
deletion); supernumerary ring 22; and a Y; 10 chromosome imbalance.
Unique’s records show no association between underbite and any particular
chromosome variation. Underbite occurred in people with a 1q21.1
microdeletion; 2q11q21 duplication; 7q11.23 duplication; 8p23 deletion; 10q23
deletion; Koolen-de Vries syndrome (17q21.31 deletion); an extra Y
chromosome; and imbalances of 3 and 7; 4 and 8; 7 and 17; and 12 and 13.
“With new technology distractors were placed in his gums with a bit either side
of a fracture, and the fracture was re-fractured daily with these devices causing
30 seconds of pain which by the old method of breaking and rewiring would have
been much more painful. The jaw lengthening is now finished. Now we are
correcting the bite and had what they called ramal hooks in at the back of his
mouth so if the orthodontist needed to he could use these somehow to
manipulate the jaw to help with teeth placement. His teeth have moved without
needing these hooks and so they were removed last week, stitches out next
week and he is looking much better in the shape of his face. However anxiety
causes him to scratch at his face, so the skin is not so good.”
Some Unique families record malocclusion, but do not specify what sort. Among
these are children with a 2q37 deletion; a small extra chromosome 2; 15q11q14
duplication; 17p13.3 duplication; 21q11q22 deletion; 22q11.2 duplication; an
extra chromosome 22; extra X chromosomes; and a mixed picture of
microdeletions and microduplications.

Crooked teeth
Crooked teeth are the most common single dental concern voiced by Unique
members. The crowding, rotation or misalignment of teeth are all particular
types of malocclusion and thus treatment is usually provided by a specialist
orthodontist. Your child’s general dentist will assess the position of the affected
tooth or teeth, and advise on treatment and the options for referral.
Unique’s records show that crooked teeth were especially common among
children with 18p deletions or ring 18; trisomy 8 mosaicism or 8p duplications;
17p13 duplications; extra X chromosomes or duplications of Xp or Xq; 22q13
deletions (Phelan-McDermid syndrome); 2q24 deletions; deletions of 4q31; 5p15
duplication; 7q35 deletion; and 21q11 deletion.
Crooked teeth also occurred in children with 1q21.1 microdeletion; 1q23q25
duplication; 1q32q42 duplication; 2p11.2p13 deletion; 2p22.3 duplication;
2q32q33 deletion; 3p25 deletion; 4p duplication; 4q28q35 duplication; 6q12q14
deletion; 6q16.3 deletion; 6q22q23 deletion; 7q22q31 duplication; 8q12q22
duplication; 9p23 deletion (Alfi syndrome); 9p duplication; 9q33q34 deletion;
11q24 deletion; 12q21 deletion; 13q13.3 deletion; 13q14q22 deletion; ring 13;

16
14q11q13 duplication; maternal uniparental disomy 14; idic 15; 15q13.3 deletion;
16p11.2 microdeletion; 16p12 deletion; 17p11.2 duplication (Potocki-Lupski
syndrome); 17q12 deletion; 18q21 deletion; 20p12.3 deletion; Emanuel
syndrome; and dual imbalances between chromosomes 1 and 6; 2 and 18; 3 and
8; 4 and 9, 10, 13, 15 or 18; 6 and 10; 8 and 12; 15 and 22; 16 and 18; 18 and 21 or
22; and 21 and the Y chromosome.

Teeth in the wrong place

Teeth may erupt in the wrong place, in particular
the upper canine teeth, which can become
impacted against the roots of the incisor teeth, or
even erupt in the roof of the mouth. These are
called impacted or ectopic canines. Your child’s
dentist will be able to say whether they can be left
alone, removed, or more complex treatment can be
done to correct the position. It is normal for
referral to be made for a specialist opinion, often to
a hospital-based paediatric dentist or orthodontist.
Unique’s records show that ectopic eruption occurs
in many children, including those with a 4p16p15
duplication; 6q16q22 deletion; 10p duplication; ring
10; 18q12q21 deletion; 20q11q13 deletion; ring 20;
an extra Y chromosome; and a 9; 14 imbalance.

Crowded teeth
Crowded teeth are a common complaint among Unique members – more so
than teeth with gaps. The cause may be big teeth, a small jaw, extra teeth, odd
tooth positions, or a mixture of any or all of these. Both first and adult teeth can
be crowded. Teeth can be so crowded they overlap, occasionally to give the
appearance of parallel rows. Crowded teeth are more prone to decay because
they are more difficult to clean. Encourage
brushing after every main meal, use a high
concentration fluoride toothpaste, and limit
sweet, sticky food and starchy foods. Fluoride
mouthwash can be difficult to use frequently
enough to be effective. The current
recommendation for home fluoride use is to use a
specially prescribed high fluoride concentration
tooth paste, and spit but not rinse after brushing.
In severe crowding, judicious extraction of some
permanent teeth may help relieve crowding and A dentist’s view of crowded
aid oral hygiene, but this should be planned very teeth
carefully and agreed by all parties involved.

17
Unique’s records show that crowded teeth were especially common among
children with 4p duplications (typically widely spaced top teeth and crowded
bottom teeth); 15q24 deletions; Potocki-Lupski syndrome (17p11.2 duplications);
18p deletions and duplications; 2q33.1 deletions; 2q13q21 duplication; 4q25q27
deletions; 6p24 terminal deletion; duplication of 9p; 18q deletions; 7q22q31/2
deletions; 14q32 deletions; and mosaic ring 22. Crowded teeth also occurred in
children with 1q41q44 deletion; 2p23p25 deletion; 2q24 deletion; 2q37 deletion;
4q31 deletion; 4p13p12 duplication; 4q28q35 duplication; 5q15q22 deletion; 5p15
duplication; 6q23q24 deletion; 7p15p14 deletion; 7q36 deletion; 8p23 deletion;
8p23p12 duplication; 9q31q33 deletion; 9q34 duplication; 10p11p12 deletion;
10p14 terminal deletion; 10q22 deletion; 10q25q26 duplication; ring 13; 14q21
deletion; maternal uniparental disomy 14; 15q25 deletion; 15q26 deletion; idic
15; 16p and 16p13.3 duplication; 16q12q22 duplication; 16q13 duplication;
22q11.2 microduplication; 22q13 deletion (Phelan-McDermid syndrome);
diploidy triploidy; an extra X or Y chromosome; Xp11.2 duplication; and dual
imbalances involving chromosomes 1 and 22; 2 and 7; 4 and 8; 4 and 10; 9 and
10; 9 and 14; 11 and 14; 12 and 13; and 6, 13 and 18.

Size
Tooth size is largely regulated by genes. Some people have bigger teeth, some
smaller. An abnormally large tooth is called a megadont. An abnormally small
one is a microdont. About 1:20 of the general population has a big difference in
the size of the top or bottom teeth. Among children with chromosome disorders,
teeth may be consistently large, or small, or of uneven sizes.

Small teeth
Word
Microdontia Small teeth
Just one or two teeth can be small, most often the teeth next to the top front
teeth (maxillary lateral incisor). Usually the root is also unusually small, but
sometimes it can be malformed. Very small teeth often lack the complex
structure of a normal-sized tooth. Gaps between very small teeth make them
easier to clean, but occasionally make biting
and chewing harder.
Some chromosome disorders are
associated with small teeth. There is a
syndrome where children are very short,
their teeth are tiny and abnormally shaped,
and the molars have no roots. This is caused
by losing the PCNT gene (21q22.3:
47,743,975-47,865,681).
Unique’s records show that tiny teeth were
Very small teeth can make biting
common among children with 6q16
and chewing harder.
deletions; 7q11.23 deletions or duplications;
18
9q34 deletions; 16p13.3 deletions and duplications. Tiny teeth also occurred in
children with 1q43 terminal deletion; 2q24.2 deletion; 2p24p21 duplication; 2q31
duplication; 3q13 deletion; 4q31 deletion; 4q32 terminal deletion; 4q34q35
deletion; 5q15q22 deletion; 7q36 duplication; 8p23 terminal deletion; 8p23p21
duplication; 9p22 terminal deletions (Alfi syndrome); trisomy9p; 10p15 deletion;
10q26 deletion; 12p12p13 duplication; 17p13.3 deletion; 17p12p10 or p11.2
duplications; 17p13.3 duplication; 22q13 deletion (Phelan-McDermid syndrome);
Xq28 duplication; extra X or an extra Y chromosome; and dual imbalances
between 4 and 20; 7 and 5 or 8; 8 and 9 or 12; X and 2 chromosome.

Large teeth
Words
Macrodontia Large teeth
Megadont A large tooth
Just one or two teeth can be very big (megadont), most often a top front tooth or
a bottom second premolar. Or all the teeth can be very big. The root can also be
unusually large.
The FGF3 gene (11q13: 69,624,735-69,634,191) can influence tooth size and
shape. When this gene is lost, as 11q13 deletion syndrome, the canine and molar
teeth are hugely enlarged and bulbous with almost no discernible cusps or
grooves. This is known as globodontia.
globodontia
Unique’s records show that large teeth were especially common among boys
with an extra Y chromosome, or extra X chromosomes, especially 3 extra X
chromosomes (49,XXXXY).
Large teeth also occurred in children with a 2q37 deletion; 3q29 deletion;
6q23q25 duplication; trisomy 8 mosaicism; inverted duplication with deletion of
8p; 9q34 deletion (Kleefstra syndrome); 12p13 duplication; 13q22q32 deletion;
16q12q22 deletion; 18q22 deletion; ring 22; Xp22.3 duplication; a complex
imbalance involving chromosomes 6; 13 and 18; and dual imbalances involving
chromosomes 1 and 17; and 13 and 18.

Taurodont teeth
Taurodont (literally, bull-like) teeth look normal in the mouth, but an X-ray will
show an abnormally enlongated pulp chamber. The pulp chamber is the part of
the tooth inside the dentine that contains the tooth’s nerves and blood supply.
Taurodontism only causes problems if there is gum disease, otherwise not.
Many genes are believed to be involved, including genes on the X chromosome.
Girls with Turner syndrome (with only one X chromosome) can have unusual
tooth roots, including very short ones. Boys and girls with extra X chromosomes
can have teeth with extra long roots.
Taurodonts, most often molars, are seen in children and adults with extra X
chromosomes; 18p11.3 deletion; Smith-Magenis syndrome; Williams syndrome;
cleft lip and palate; and 1/3 people with Down syndrome, as well as a range of
other non-syndrome chromosome disorders.
19
Unusually shaped teeth
Words
Double teeth Joined teeth Fused teeth Geminated teeth
Odd-shaped teeth can grow separately, or be fused with a neighbouring tooth.
When they are fused, the double tooth can be joined at the crown, the roots or
both. Double teeth are more common in first teeth, usually the bottom front
teeth. The teeth most often involved are the front teeth and the first canines.
When first teeth are fused, it is more common for the adult tooth to be missing.
Fused teeth occurred in children in Unique with a 1q21 deletion; 4q21 deletion;
4q32 terminal deletion; 7q11.22 deletion; 7q31q34 duplication; 7q36 deletion;
11q23 triplication; trisomy 14 mosaicism; 17q24 triplication; a 4; 18 imbalance.
Similarly, a single root can give rise to two tooth
crowns.
Teeth can be curved or rounded; jagged or crinkly on
the incisal edge; triangular; peg-shaped; or square.
The front teeth can have a cusp on the tongue side (so
-called ‘talon cusp’), or alternatively be hollowed out
into a ‘shovel’ shape. Most of these variations have Fused baby teeth, with
many causes, and some depend partly on ethnic decay
origin. First and adult upper molars can often have an
extra cusp on the palate side.
Unique’s records show no particular disorders where
unusually shaped teeth are common. They occurred in
children with 2p13 deletion; 2q24 deletion; 2q11.2q21
duplication; 3q27 deletion; 4p duplication; 7q31q33
Fused adult teeth
deletion; 5q15q22 deletion; 7p15p12 deletion; 7q35
deletion; 10p15p11.2 duplication; 10q26.3 deletion;
trisomy 14 mosaicism; 15q26 interstitial deletion;
16q22q24 deletion; 17p11.2 duplication (Potocki-
Lupski syndrome); multiple extra X chromosomes;
and dual imbalances between chromosomes 4 and 7,
8 or 22; 7 and 18; 8 and 2 or 3; and 9 and 20.
When one of the upper lateral incisor teeth is missing,
the one on the other side is sometimes peg-shaped.
Specifically peg-shaped, small teeth were seen in
children with 7q22q31 duplication; an extra Y
chromosome; and dual imbalances between
chromosomes 4 and 20; and 5 and 6.
Sharp conical teeth have been seen in children with a Canines (cuspids) are
1q21.1 deletion; a 7q34 deletion; a 14q32 duplication; ‘fang’-like in a child with
an extra X chromosome; and a dual imbalance Pierre Robin sequence
between chromosomes 4 and 8. and small jaw

20
The shape of teeth can be chiefly cosmetic, but it can
also cause problems with occlusion, biting and
chewing. If needed, the abnormal tooth shape can
often be easily disguised by use of bonded tooth-
coloured resin materials. This requires good co-
operation for the bonding steps and shaping to be
carried out, but no injections, drilling or damage to the
teeth should be needed. Always resist or question
offers by a dentist to file down pointed teeth or drill
the tooth in preparation for a permanent crown. These Irregular teeth
procedures are irreversible, may leave the tooth very
sensitive, and should not be considered until young adulthood.

Poor enamel and dentine

Poorly developed enamel can be generally thin, or have pits, ridges and grooves
in its surface. When the tooth comes through, the enamel can turn a buff,
orange or brown colour and is quickly and easily worn away. Sometimes just one
tooth is affected, or a group of teeth, or all the teeth.
Most enamel defects are not genetic in origin. A useful source of information is
the website http://www.thed3group.org.
When more than one adult tooth has poor enamel, the cause can be illness in a
baby or a serious nutritional deficiency while the tooth was forming. A
disturbance around the time of birth can affect the tips of the front adult teeth
and the biting surfaces of the first adult molars, as well as the first teeth. This is
because the cells that lay down the enamel are among the cells in the body that
have the most sensitive nutritional needs.
Genes on the X and Y proteins give instructions for making amelogenin, the most
abundant protein in the formative tissue of tooth enamel. A gene on the X
chromosome (AMELX, see Genes) accounts for the great majority of the protein.
Poor enamel formation and poor dentine can be hard for a parent to distinguish.
You may only see that your child’s tooth or teeth are a normal shape but look
blue-brown, shiny and translucent (opalescent) and are soft. Often the dentine is
affected and the enamel covering breaks down because the
dentine beneath is weak. Exposed dentine then rapidly
wears away so the teeth look short. In severe cases the
teeth can wear down almost to the gums. In other cases,
the teeth have to be coated, sealed, extracted, or capped or
crowned with steel or porcelain. In many children with a
chromosome disorder tooth grinding makes this worse.
First teeth are usually more affected than adult teeth, but
Enamel defect on a both are involved.
molar tooth The most common dental genetic disease is dentinogenesis
imperfecta type II. The gene underlying this condition has

21
been mapped to 4q, as have some of the proteins that make up the enamel.
Defective tooth enamel (amylogenesis imperfecta) has also been found in
children with 4q deletions. It is then no surprise to find that many children with a
4q deletion, specifically between 4q12 and 4q21, are reported to have poor teeth.
Unique’s records show that poor enamel was especially common among
children with a 4q12q21 deletion; trisomy 8 mosaicism and boys with extra X
chromosomes, especially 48,XXXX. It was found repeatedly among children with
a 4p duplication; 5q15q22 deletion; a 5q35 deletion; 6p24/5 deletion; 8p23
deletion; a 17q21.31 deletion (Koolen de Vries
syndrome); and a 22q11.2 deletion.
Poor enamel also occurred in children with a 1q21.1
deletion; 1p36 duplication; 2q37 deletion; 3p26
deletion; 4p12 deletion; 7q21q22 deletion; 7q34
deletion; 7q31 deletion; trisomy 9 mosaicism; 10q25
deletion; 11q23 triplication; Pallister Killian
syndrome; 13q31 terminal deletion; 14q12
Dentine defect affecting
duplication; 15q12 deletion; 17p12 duplication; 17q12
first teeth
deletion; 18p deletion; 18q23 deletion; 19p13.3
deletion; ring 20; ring 22; trisomy 22 mosaicism; and
Yq11.23 deletion. It also occurred in children with dual imbalances between
chromosomes 1p and 22q; 2q and Xq; 3p and 16p; 4p and 20p; 4q and 22q; 8 and
9; 9 and 18; and 14 and 22. A child with an imbalance between 4 and 22 had teeth
so soft they could not hold a filling.
Unique’s records show that decay was especially common among children with
an 18p deletion; extra X chromosomes, XXYY or other X chromosome variations,
including Xp11.23 duplication.
It was found repeatedly among children with 2q37 deletion; 6p terminal deletion;
7q21 deletion; 10q26 deletion; 13q22q32 deletion; 16p11.2 deletion; 17p12p10
duplication; 22q13 deletion.
It was also found in children with 1p36 deletion; 1q42 deletion; 2q12q13 deletion;
2q13 duplication; 2q32 deletion; 2q duplication; 3q21q26 duplication; 3q28
deletion; 3q25 duplication; 4q27 duplication; 5p15 duplication; 6q26 deletion;
7q11.2 deletion; duplication of 7q11.23; 8p11p21 deletion; inverted duplication of
8p; 9p22 deletion; 9p24 deletion (Alfi syndrome); tetrasomy 9p; 9q12q21
deletion; trisomy 9 mosaicism; 10q duplication; 11p duplication; 11q25 deletion
(Jacobsen syndrome); 12p duplication; 12q21 deletion; 14q deletion; 15q11.2
deletion; 15q11q14 duplication; 15q13.3 deletion; 15q22.3 duplication; 16p11.2
duplication; 17p11.2 deletion (Smith Magenis syndrome); 17p11.2 duplication
(Potocki Lupski syndrome); 17q21.31 deletion; tetrasomy 18p; 18q23 deletion;
20q11.2q13 deletion; 21q11q21 deletion; Xp11.23 duplication; XYY; and
imbalances between 1q44 and 8q21; 3p25 and 8q22; 4p16 and 8p23; 4p16 and
20p13; 4q25 and 9p22; 5q27 and 3q25; 5q34 and 6p24;16p12p13 and Xp11.23.

22
Some genes
Many genes are involved in tooth development. The list below includes some
that are known about, but much remains to be discovered.
IRF6: 1q32.2 1:209,958,000-209,979,000 Deletion linked with missing teeth
EDA Xq13.1 X: 68,835,00-69,259,000 This gene is important in regulating tooth
number. Disruption in the gene can cause teeth not to grow. Changes
(mutations) can cause a syndrome involving the hair, skin and teeth.
EDARADD 1q42.2q43 1: 236,557,-236,648,000 Changes (mutations) cause
abnormal teeth, hair and skin
WNT10A 2q35 2: 219,745,000-219,764,000 Important in regulating tooth
number. Disruption can cause teeth not to grow. Implicated in mild ectodermal
dysplasia-type conditions.
PTH1R 3p21.31 3: 46,919,00-46,945,00 Changes (mutations) are linked with
teeth that never appear.
TP63 3q28 3: 189,348,000-189,615,000 A number of syndromes involving the
skin and hair, with a wide range of tooth defects
MSX1 4p16.2 4: 4,486,000-4,865,000 Changes (mutations) linked with missing
teeth, specifically second premolars and third molars. First teeth are usually
normal. Other mutations of this gene lead to different patterns of missing teeth
ENAM 4q13.3 4: 71,494,000-71,512,000 Changes (mutations) cause poorly
formed enamel, and a syndrome called amelogenesis imperfecta
DSPP 4q22.1 4: 88,529,00-88,538,000 Changes (mutations) in the dentin
sialophosphoprotein gene play a role in dentine defects.
PITX2 4q25 4: 111,538,000-111,563,000 Certain changes (mutations) lead to
abnormal tooth development
APC 5q22.2 5: 112,043,000-112,181,000 Changes (mutations) are linked with
extra teeth
SHH 7q36.3 7: 155,595,000-155,604,000 Many different changes (mutations) in
the SHH gene can cause problems with the development of the face, including
the teeth especially around the middle of the upper jaw
RECQL4 8q24.3 8: 144,511,00-144,517,000 This gene is important in bone
formation, and changes (mutations) are linked with tooth defects including short
roots
FAM83H 8q24.3 8: 144,806,000-144,822,000 This gene is needed for proper
incorporation of calcium into dental enamel.
LTBP3 11q12 11: 65,306,000-65,325,000 Changes (mutations) in this gene have
been linked with specific missing teeth
MMP20 11q22.2 11: 102,447,000-102,496,000 This gene plays a central role in
forming tooth enamel, and changes (mutations) are linked with the poor enamel
syndrome called amelogenesis imperfecta
UBR1 15q15.2 15: 43,235,000-43,398,000 Changes (mutations) cause a disorder
known as Johansson-Blizzard syndrome with tooth problems that include late
first teeth, small teeth, and multiple missing adult teeth.

23
WDR72 15q21.3 15: 53,805,000-54,055,000 Deletions and changes (mutations)
can cause imperfect enamel formation (amelogenesis imperfecta).
DLX3 17q21.33 17: 48,067,000-48,072,000 Changes (mutations) in this gene can
cause enamel defects (amelogenesis imperfecta), small and underdeveloped
teeth, or large teeth with enlarged pulp chambers (the part of the tooth inside
the dentine that contains the tooth’s nerves and blood supply).
AX1N2 17q24.1 17: 63,524,000-63,557,00 Changes (mutations) are linked with
missing adult teeth.
KLK4 19q13.41 19: 51,409,00-51,413,000 Important in very early tooth
formation. Changes (mutations) have been linked with enamel defects
(amelogenesis imperfect).
BCOR Xp11.4 X: 39,910,000-40,036,000 Deletions and changes (mutations) can
cause syndrome with missing teeth, late adult teeth and very large roots and
crowns of several front teeth and canines.
AMELX Xp22.2 X: 11,311,00-11,318,000 Vital for proper enamel formation.
Deletions and changes (mutations) can cause enamel defects, including
amelogenesis imperfect.
IKBKG Xq28 X: 153,769,00-153,796,000 Deletions and changes (mutations) can
cause skin, hair and tooth defects, as well as immune deficiencies.

Some syndromes
18p11.3 deletion
Many dental anomalies, including teeth that are late to appear, irregular teeth,
decay, enlarged taurodont teeth and problems caused at the middle of the upper
jaw caused by irregularities at the midline.
22q deletion
Dental problems include poor tooth enamel, excess cavities and crooked teeth.
Rieger syndrome
PITX2 mutation causes changes to the front part of the eye, and hypodontia,
leading to some missing first and adult teeth, most often front and canine teeth.
Other tooth anomalies include poor enamel formation, cone-shaped teeth, short
roots, taurodontism, and teeth late to come through. The dental anomalies
differentiate Rieger syndrome from Axenfeld-Rieger malformation. Genes
involved apart from PITX2 are FOXC1 and GJA1.
Cleidocranial dysplasia
Dental anomalies in children with cleidocranial dysplasia can include first teeth
that are very late to fall out, late eruption of adult teeth, supernumerary (extra)
teeth and misalignment of the teeth and jaws. Changes (mutations) in the
RUNX2 gene (6p21: 45,328,000-45,551,000) are the cause.
Down syndrome
70 per cent of females and 90 per cent of males with Down syndrome have some
missing teeth. Taurodont teeth are seen in around one in 3. Crowns and roots
are frequently short, apparently reflecting general growth delay in the

24
developing teeth. Teeth generally erupt late.
Holoprosencephaly
Failure in the process by which the brain divides into right and left hemispheres,
associated with severe facial anomalies but sometimes seen only with a single
front tooth. Numerous genes identified, most commonly SHH at 7q36.3, but also
SIX3 at 2p21; TG1F at 18p11.3; ZIC2 at 13q32; and PTCH at 9q22.
KBG syndrome (ANKRD11 changes)
Large permanent upper central incisors
Langer-
Langer-Giedion syndrome
Dental anomalies include tiny teeth, late eruption, and extra teeth. Deletions and
changes (mutations) in TRPS1 (8q23.3: 116420723-116713298) are the probable
cause.
Rubinstein-
Rubinstein-Taybi syndrome & 16p13.3 duplication
Caused by deletion of CREBBP in 16p13.3. Dental effects include a specific type
of cusp called a talon cusp; screwdriver-shaped front teeth; thin enamel; and
over- or under-bite. Duplication of 16p13.3 has only recently been identified but
small teeth are common.
Williams-
Williams-Beuren syndrome 7q11.2 deletion
Affected people have a range of dental anomalies including missing teeth, small,
screwdriver-shaped incisors, and significantly short roots, as well as taurodont
teeth.
Wolf Hirschhorn syndrome
Dental anomalies include late eruption; fused front teeth; oligodontia; and
missing teeth. Oligodontia is probably caused by the loss of MSX1 at 4p16.2.
Smith Magenis syndrome
Dental anomalies are common, and include missing teeth, most often the
premolars and incisors; small crowns; screwdriver-shaped or tapered teeth;
taurodont teeth; sharp bends or curves in the root or crown of the teeth; and
protrusion of the lower front teeth.
Sotos syndrome
Early emergence of the teeth; malocclusion; irregular teeth; excess wear and
staining.
Syndromes with extra X chromosomes
Taurodont teeth.

25
References
Developmental Disorders of the Dentition: An Update Klein et al 2013:
American Journal of Medical Genetics Part C 163C: 318-332.
The genetic basis of inherited anomalies of the teeth. Part 1: Clinical and
molecular aspects of non-syndromic dental disorders.
Bailleul-Forestier et al 2008: European Journal of Medical Genetics 51(4): 273-
91.
The genetic basis of inherited anomalies of the teeth. Part 2: Syndromes with
significant dental involvement. Bailleul-Forestier et al 2008 51(5): 383-408.
Diseases of the tooth: the genetic and molecular basis of inherited anomalies
affecting the dentition. Cobourne and Sharpe 2013: WIREs Dev Biol 2013, 2: 183-
212. doi: 10.1002/wdev.66.
Dental agenesis: genetic and clinical perspectives. De Coster et al 2009. Journal
of Oral Pathology in Medicine 38(1):1-17.
Genetic basis for tooth malformations: from mice to men and back again.
Mitsiadis et al 2011: Clinical Genetics 80: 319-329.
Tooth Evolution and Dental Defects: From Genetic Regulation Network to Micro-
RNA Fine-Tuning. Michon 2011. Birth Defects Research (Part A) 91: 763-769.

Resources
British Society for Disability and Oral Health www.bsdh.org.uk
www.dentalphobia.co.uk

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Notes

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2014 Version 1(PM)
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