Oral manifestation of waardenburg syndrome: A case report and review of the literature

Abstract

Waardenburg syndrome is a rare autosomal dominant genetic disorder of neural crest cell migration. It is characterized by congenital sensorineural hearing loss, heterochromia iridis, depigmentation of hair and skin, and increased intercanthal distance. It is subdivided into four subtypes with I and II being most common. These subtypes are categorized based on genetic mutations. Even although medical literature has well documented this syndrome, dental and radiographic findings have been rarely presented. In this case report and literature review, we have presented and discussed oral as well as head and neck radiology findings of a 20-year-old girl with Waardenburg syndrome.

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Cite this article as:
Jagtap R, Alansari R, Ruprecht A, Kashtwari D. Trichodentoosseous syndrome: a case report and review of literature. BJR Case Rep 2019;
5: 20190039.
CASE REPORT
Trichodentoosseous syndrome: a case report and
review ofliterature
ROHAN JAGTAP,BDS, MHA, RAGHD ALANSARI,BDS, AXEL RUPRECHT,DDS, MScD, FAAOMR, FRCD(C), FICD, FACD and
DEEBA KASHTWARI,BDS, MS
Department of Oral and Maxillofacial Diagnostic Sciences, University of Florida College of Dentistry, Gainesville, FL, USA
Address correspondence to: Dr Rohan Jagtap
E-mail: RJagtap@ dental. ufl. edu
In 1972, Lichtenstein coined the term “trichodentoosseous”
(TDO) syndrome for a rare autosomal dominant disorder
caused due to a mutation in the DLX3 gene on chromosome
17q21.1,2 According to the National Foundation of Ectoder-
mal Dysplasia, some of TDO aected individuals inherit
the mutated gene whereas others experience spontaneous
gene mutation. TDO is subdivided into three types TDO
I, II, and III based on clinical and radiographic features.1
Since this syndrome is rare, there is a limited number of
the reported cases which makes it dicult to determine
whether all reported ndings, other than the pathogno-
monic ones, are part of TDO. Moreover, its rareness in the
literature results in a lack of epidemiological data.3
TDO is characterized by abnormal development of ectoder-
mally derived structures. Dysplastic nails, curly hair, bone
sclerosis, taurodontism, and amelogenesis imperfecta are
common features of this disorder.1,3,4 Additionally, some
cases report maxillofacial ndings such as mandibular prog-
nathism, periapical abscesses, taurodontism, amelogenesis
imperfecta, and impacted teeth.4–6 Of the other maxillofa-
cial ndings, taurodontism and amelogenesis imperfecta
are consistently seen with TDO, whereas other non-dental
abnormalities are variably, present. Some studies have even
shown variability in non-dental features among the aected
individuals who belong to the same family.4
e absence of the non-dental ndings could confuse clini-
cians because TDO overlaps with amelogenesis imperfecta
hypomaturation-hypoplastic type (AIHHT) in that both of
them are characterized by taurodontism and enamel hypo-
plasia.2 However, the key factor to dierentiate between
them is that taurodontism associated with TDO is mostly
conned to mandibular rst permanent molars, whereas
taurodontism associated with AIHHT could be seen in any
molars.7
We present a classic case of TDO syndrome with orid
osseous dysplasia (FOD) in the maxilla and mandible.
CASE PRESENTATION
A 22-year-old male presented to the University of Florida
College of Dentistry, Oral and Maxillofacial Surgery clinic
with a chief complaint of “I want to look at treating my jaw.”
e patient reported a poor dentition his entire life, and he
feels that his teeth have been “falling apart.” e remainder
Received:
15 April 2019
Accepted:
12 July 2019
Revised:
05 July 2019
https:// doi. org/ 10. 1259/ bjrcr. 20190039
ABSTRACT
Trichodentoosseous (TDO) syndrome is a rare autosomal dominant condition characterized by various dental and
non-dental findings such as taurodontism, amelogenesis imperfecta, osseous dysplasia, mandibular prognathism, curly
hair, dysplastic nails, which may be symptomatic or asymptomatic. TDO syndrome is divided into three subtypes
that helps to categorize dierent features seen in patients. There are very few cases reported in the literature of TDO
syndrome. We present a case of a young adult male showing interesting Type I and II clinical and radiographic findings
of the TDO syndrome. Amelogenesis imperfecta hypomaturation-hypoplastic type and TDO syndrome overlaps in their
dental findings such as taurodontism and enamel hypoplasia and makes the diagnosis of TDO crucial. TDO syndrome
was noted as an incidental finding on cone beam CT. This case report highlights the pathognomonic radiographic find-
ings, treatment plan, and the clues to diagnosis this rare disorder. Management of TDO requires a proper diagnosis,
multidisciplinary approach with comprehensive treatment plan including periodic follow up. Knowledge of this condi-
tion along with thorough interpretation of the entire cone beam CT volume are critical to understand this syndrome
better due to its rarity.

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of the medical history was noncontributory. ere was no rele-
vant family history, and he denied a history of pain, numbness/
paresthesia, facial asymmetry, or drainage. Intraoral examina-
tion revealed condyloma acuminatum on the lower lip.
A pantomograph was made as part of the diagnostic work-up
which revealed mixed radiopaque lesions in the maxilla
and mandible with multiple impacted and malformed teeth
(Figure 1). Based on the clinical and radiographic ndings, a
cone beam CT (CBCT) volume was made.
e CBCT depicts a generalized multilocular mixed radiopaque
appearance in the tooth-bearing regions of both jaws with the
trabecular pattern having a mixed lytic and sclerotic appear-
ance (Figures1 and 2). ere is absence of enamel in multiple maxillary and mandibular teeth (Figures 1 and 2). ere is
elongated pulp chamber, apically positioned furcation, short-
ened roots are noted in tooth #19 and molars of right side. e
morphology of many of these teeth is consistent with tauro-
dontism (Figure2). ere are multiple large radiolucent spaces
within the bone (Figure 2). ere is enlargement in several
regions of the mandible and maxilla, especially in the le side of
the mandible (Figure3). ere is thinning of the buccal cortical
plate on the le side of the mandible and disruption of the lingual
cortical plate (Figures4 and 5). e radiographic interpretation
is consistent with FOD with associated simple bone cysts, tauro-
dontism, and amelogenesis imperfecta.
DISCUSSION
Jorgenson et al described dental abnormalities in TDO patients
as dense bony cortex, amelogenesis imperfecta, and multiple
impacted teeth.8 Our case reports the occurrence of four signif-
icant ndings of TDO syndrome, i.e. FOD, amelogenesis imper-
fecta, taurodontism, and Class III malocclusion. Having all
these lesions together in one patient is rare. FOD is a condition
conned to the tooth-bearing regions of the jaw.9 It is considered
a widespread form of a periapical osseous dysplasia, in which
the dense osseous tissue in a background of brous connective
tissue replaces normal cancellous bone.10 Various hypotheses
have been postulated with regard to FOD’s pathogenesis, but
the real cause remains unknown. Middle-aged black females
are the most aected group. e bilateral posterior mandibular
bodies are the most oen reported sites, but the maxilla also can
be aected.9 FOD is usually diagnosed as an incidental nding
since this condition is mostly asymptomatic. e radiographic
Figure 1. Panoramic view: depicting mixed density lesions
in maxilla and mandible. The inferior alveolar canals are
displaced inferiorly, especially on left side (yellow arrow).
Figure 2. Sagittally reconstructed CBCT of the jaws depicting
a mixed-density lesion in the maxilla and mandible containing
teeth. There is elongated pulp chamber, apically positioned
furcation, shortened roots are noted in tooth #19 and molars
on right side, consistent with taurodontism (red arrow). Inferi-
orly displaced left inferior alveolar canal (yellow arrow). CBCT,
cone beam CT.
Figure 3. Coronally reconstructed CBCT of the jaws depicting
a mixed lytic trabecular pattern and displacement of buccal
cortical plate (white arrows). Taurodontism with shortened
roots noted in #19 (red arrow). Superiorly displaced floor of
the left maxillary sinus (yellow arrow). CBCT, cone beam CT.

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appearance varies from complete radiolucent through mixed
(radiopaque-radiolucent) to complete radiopaque lesions.9,10
Treatment or intervention such as biopsy are not recommended
in FOD patients, rather observation and periodic radiographic
follow-up are advised. Avoidance of intervention is to obviate
complications like prolonged poor healing and secondary
infection which can lead to osteomyelitis or jaw fracture.9 e
dierential diagnosis of FOD includes Paget disease of the bone,
chronic sclerotic osteomyelitis, and Gardener syndrome. Paget
disease is commonly seen in white males, and has an increase
in serum alkaline phosphatase levels.9,10 Radiographically, Paget
disease aects the entire mandible whereas FOD aects the body
of the mandible superior to the inferior alveolar canal. Chronic
sclerotic osteomyelitis tends to be unilateral rather than bilat-
eral, and it is not conned to the tooth-bearing region of the jaw.
Gardner syndrome presents other skeletal changes such as oste-
omas, skin tumors or dental anomalies such as multiple odon-
tomas, which is not the case in FOD.9
Amelogenesis imperfecta (AI), also known as congenital enamel
hypoplasia, is a genetic abnormality that is characterized by
abnormal enamel formation, which makes the teeth looks small,
discolored, pitted or grooved, and prone to rapid wear and
breakage.6,11 Both the deciduous and permanent dentitions can
be aected. Researchers have found that the cause is a mutation
in some genes that are responsible for protein encoding.6 is
mutation can be inherited or due to a spontaneous gene mutation.
AI is classied into 17 types based on the gene mutation pattern;
however, in relation to clinical and radiographic appearance,
there are four main types.11 First, hypoplastic AI type is char-
acterized by thin, rough, pitted, and discolored enamel with
lack of the normal proximal contour, radiographically the teeth
appear to have square-shaped crowns, a thin radiopaque layer
of enamel, and multiple open contacts.6,10 Second, hypomatura-
tion type AI is characterized by so, brown colored enamel of
normal thickness, but with a radiopacity similar to dentin. ird,
hypocalcied type AI is characterized by brittle, orange-brown
colored enamel of normal thickness which has less radiopacity
than dentin. Fourth, hypomaturation–hypoplastic with tauro-
dontism type AI is characterized by thin, pitted, mottled, white–
yellow–brown colored enamel which has a similar or greater
radiopacity than dentin.6 Amelogenesis imperfecta can occur
alone without any other signs and symptoms, or it can occur as
part of a syndrome that aects multiple parts of the body.6,11
Taurodontism is a developmental dental anomaly that aects the
morphology of molars producing wide pulp champers and, an
apically positioned furcation thought to be due to disturbances
in Hertwig's epithelial root sheath invagination.12 Taurodontism
is most commonly found in the permanent dentition. It can be
isolated, or as part of a syndrome such as Klinefelter, Down, or
TDO syndrome.13 Radiographs are needed as the diagnostic tool
that can be used to investigate a taurodont tooth as the external
coronal morphology is within the range of normal.
As mentioned in the introduction TDO has three types. e rst
type shows the abnormal density of bone whereas the calvarium
Figure 4. Coronally reconstructed CBCT of the left side of
the mandible: depicting thinning of the buccal cortical plate.
CBCT, cone beam CT.
Figure 5. Axially reconstructed CBCT of the jaws depicting
buccolingual enlargement and disruption of the lingual
cortical plate. CBCT, cone beam CT.

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is within normal density. In addition, the patient displays sign of
dolichocephaly due to early closure of the skull’s suture. Other
features such as delayed teeth eruption, teeth discoloration, and
malformed nails are seen in TDO-I. In the second type of TDO,
calvarium exhibits osseous changes involving osseous dysplasia.4
Moreover, premature tooth eruption, curly hair, and dysplastic
nails are observed among TDO-II aected individuals. In the
third type, calvarium experiences changes in the thickness,
however, the bone density is within normal range. Furthermore,
macrocephaly is a marker sign of TDO-III.1 Our case demon-
strates radiographic features from both TDO types I and II.
e rareness of TDO and limited reported cases are the main
reasons that makes the agreement on specic signs debatable.
Mandibular prognathism, dolichocephaly, periapical abscesses,
and impacted teeth have been observed among the aected
individuals.4,5,13 However, our case presents the reported radio-
graphic features of enamel hypoplasia, rst molar taurodontism,
mandibular prognathism, impacted teeth, periapical abscess,
and osseous dysplasia. Tight curly hair is one of the non-dental
diagnostics ndings, and indeed our patient has curly hair,
but since our patient is an African American, we cannot attri-
bute the hair curling to TDO. Taurodontism and enamel hypo-
plasia are the most common dental ndings for TDO as well as
for AIHHT.2,6,7 e confusion between these two conditions
would be increased with the absence of the non-dental ndings
since there is variability in the presence of the non-dental nd-
ings. However, taurodontism which is associated with TDO is
present only in mandibular rst permanent molars which is not
in case of AIHHT.7 Based on these markers, some researchers
disagreed with certain reported cases diagnosed with AIHHT.4,7
For instance, the presence of taurodontism and curly hair in the
family of the AIHHT reported case by Congleton and Burkesis
led the researchers to believe that case is misdiagnosed as AIHHT
instead of TDO.4 In our case, we have diagnosed the condition as
TDO based on the pathognomonic radiological features.
e management of TDO aected individuals require a multi-
disciplinary approach involving both dentists and physicians.
Periodic radiographic follow-up is required to prevent or long-
term manage further complications such as osteomyelitis.13
In our case, FOD is one of the features that the patient has,
which does not need any treatment unless it becomes second-
arily infected, but it needs to be observed through periodic
radiographic examination.9 Since TDO patients are prone to
attrition, caries, abscesses and pulpal infections, prophylactic
treatment and relieving pain play a primary role in TDO
management.13,14 In addition, treatment of aesthetic defects and
resultant psychological trauma are also important. Treatment
of aesthetic defects resulting from amelogenesis imperfecta has
shown to provide a marked increase in self-esteem of aected
individuals as reported by Lindunger et. al.15 is restoration can
be done through operative, prosthodontic, orthodontic, and/or
endodontic intervention.13
CONCLUSION
TDO syndrome is rare syndrome whose rareness has led to a
lack of enough reported cases, which aects general knowledge
about this syndrome. However, some signs have been found
consistently in TDO aected individuals. Some of these signs
also occur with AIHHT, but involvement of only the mandibular
rst permanent molar and a history of hair and nail defects could
be used as distinguishing features. Genetic investigations can
be helpful since the cause of this condition is a mutation in the
DLX3 gene and could aect other family members. Treatment
considerations are conned to each of the features that patients
have. It is important to recognize multiple abnormalities associ-
ated with this syndrome radiographically. More reports of TDO
syndrome with long-term follow-up information would help to
understand this syndrome better.
LEARNING POINTS
1. TDO syndrome is rare autosomal dominant disorder.
2. Based on clinical and radiographic features, TDO is
subdivided into three types TDO I, II, and III.
3. TDO is characterized by abnormal development of
ectodermally derived structures with dysplastic nails,
curly hair, bone sclerosis, taurodontism, and amelogenesis
imperfecta are common features.
4. The absence of the non-dental findings could confuse
clinicians as TDO overlaps with AIHHT that both of them
are characterized by taurodontism and enamel hypoplasia.
5. Treatment considerations are confined to each of the
features that patients have. It is important to recognize
multiple abnormalities associated with this syndrome
radiographically. More reports of TDO syndrome
with long-term follow-up information would help to
understand this syndrome better.
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