Vol.2, No.10, 1199-1203 (2010) Health
doi:10.4236/health.2010.210176
Copyright © 2010 SciRes. Openly accessible at http://www.scirp.org/journal/HEALTH/
Dental treatment of twin monozygotic brothers with
fragile X syndrome
Flavia Melo Meira, Luis Candido Pinto Silva, Regina Haddad Rezek Ferreira,
Roberval Almeida Cruz*
Department of Dentistry, PUC Minas, Belo Horizonte, Brazil; *Corresponding Author:
[e-mail]; ;
Received 3 August 2010; revised 12 August 2010; accepted 26 August 2010.
ABSTRACT
Fragile X syndrome (FXS) is the main cause of
inherited mental retardation and is the result of
transcriptional silencing of the fragile X mental
retardation gene FMR1. An absence of the as-
sociated protein FMRP leads to the deregulation
of many genes, which results in phenotypes of
Attention-Deficit Hyperactivity Disorder (ADHD),
anxiety, epilepsy and autism. The aim of this
article is to report the clinical case of twin sib-
lings affected by FXS and to describe the pro-
cedures for dental treatment with intravenous
sedation. Information regarding the character-
istic manifestations of FXS not only aided in the
handling of the patients but also enabled us to
develop clinical programs to promote and
maintain oral health using individualized and
specific dental procedures.
Keywords: Syndromes Head and Neck/cleft Lip
and Palate; Fragile X Syndrome; Pain
Control/Sedation; Oral Medicine
1. INTRODUCTION
Fragile X syndrome (FXS) is the most commonly inher-
ited form of mental disability in men and to a lesser ex-
tent in women due to the presence of a single chromo-
some X. Its prevalence is estimated to be 1:4000 in men
and 1:6000 in women. It is the most frequent manifesta-
tion of intellectual impairment after Down syndrome, a
main cause of hereditary mental retardation [1-6].
FXS’s name is derived from an existing constriction
in the long arm (q) of chromosome X in the area of the
mutated gene FMR1 (Fragile X Mental Retardation 1).
The protein coded by this gene is called FMRP (Fragile
X Mental Retardation Protein). FMRP was sequenced in
1991, and it is predominantly expressed in the brain and
gonads. Although its exact function is still unknown, its
properties and location suggest that it is involved in
regulating the transport, stability and translation of some
mRNAs. FMR1 may affect the mRNAs of proteins by
activating or inactivating their production [7,8]. Most of
the mRNAs that are identified as targets of FMR1 are
involved in some aspect of synaptic structure, and their
corresponding proteins are involved in the formation of
memory and learning. It is very probable, therefore, that
the cause of the mental deficiency produced by FXS is
due to an absence of FMRP in the synaptic junction [9].
The carriers of this condition usually do not show
phenotypic manifestations, but they do have the risk of
generating affected offspring. In general, the pre-muta-
tions can become complete mutations remaining un-
known the accurate time when this happens, may be dur-
ing the gametogenesis or during the start of embryonic
development. Thus women with 55-200 CGG repeats
have a greater risk of transmission due to allelic instabi-
lity. When the mutation exceeds 200 repetitions, it is
called a full mutation and this causes methylation of the
promoter region with the consequent repression of the
gene FMR-1. This gene repression then results in the
absence of protein FMRP expression. As a consequence,
mental retardation and other clinical characteristics of
FXS are manifested [10,11].
Among the most common physical characteristics, be-
sides the mental retardation of variable intensity, are
large everted ears, a long face, hyper-extendable articu-
lations, short and thick fingers and macro orquidism.
Also described are wide eyelids rifts, a large skull rela-
tive to the trunk, epicanthic pleats, eyes that squint, hy-
potonic muscles, short-sightedness, a prolapse of the mi-
tral valve, dilation of the aorta, suction calluses on the
hands and fingers, flat feet and a unique palm line
[12-14]. To a lesser extent, symptoms of neurological
problems have been reported, such as hyperreflexia,
nystagmus and epilepsy [15]. The characteristics of den-
tal interest are mandibular prognathism, macroquilia,

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macroglossia, ogival palate and alterations in the dental
enamel. These symptoms cause dental tissue exposition,
and this condition cannot be attributed to physiological
attrition [16].
Patients with the FXS have very peculiar personalities.
Some disturbances of behavior that have been reported
include shyness, anxiety, panic and violent attacks, de-
fense or avoidance of tactile contact, explicit memory, a
sense of humor and an excellent ability to imitate. FXS
patients are very attached to their immediate environ-
ment, and some cannot filter noise and light and such
stimuli can trigger hyper-activity symptoms, attention
deficit and impulsiveness. The sensory system in these
individuals does not always respond appropriately, and
they can react in a negative way to some types of tactile
stimuli. Certain stimuli can be responsible for the exhi-
bition of autistic behavior, such as turning the hands and
biting them, stereotypical movement of the limbs and
poor visual contact. Speech is severely impaired, and the
development of language is limited until approximately
two or three years of age. They possess little verbal
communication skills and poor articulation of words.
Speech is exhibited in a noisy way, in an irregular rhy-
thm and in an expressive tone to emphasize emotions or
to reinforce the meanings of words [17].
Recent studies report a new condition that has been
called Fragile X-associated Tremor/Ataxia Syndrome
(FXTAS). This new classification includes a group of
neurological symptoms typically associated with elderly
men who also carry the pre-mutation for the gene FMR1.
The alterations in behavior include tremor, walking and
balance difficulty, anxiety and loss of memory [18,19].
The aim of this article is to report the clinical case of
twin siblings affected by FXS and to describe the pro-
cedures for dental treatment with intravenous sedation.
2. CASE REPORT
Genetic information might have health and reproductive
implications for the patient and their family members.
The responsibility for communicating this information
within families generally lies with the patient or genetic
counselor [20]. In this way, 13-year-old male (Figure 1)
Figure 1. Facial aspect of twin siblings with the fragile
X syndrome.
monozygotic twins with fragile X syndrome were re-
ferred for treatment to the Dental Clinic for Patients with
Special Needs at the Catholic University of Minas
Gerais.
At admission, the mother indicated that the period of
gestation proceeded normally. In the first year of the
children’s lives, a delay in neuropsychomotor develop-
ment was detected. The children were hyperactive and
began walking at around 2 years of age. At 7 years of
age, they were referred to Sarah Kubitschek Hospital for
genetic analysis, and at that time, they were diagnosed
with fragile X syndrome.
The behavior of the twins could be defined with suffi-
cient clarity. At first, it was observed that the twins had a
degree of moderate mental retardation, hyperactivity,
poor visual contact, echolalia, and problems in speech
particularly in the pronunciation of words. According to
the mother, they exerted the majority of their activities
independently, learned slowly, showed anxiety, and had
a sharpened memory, an excellent sense of humor and a
capacity for imitation. Certain stimuli resulted in panic
and they drew violent pictures, such as moving buses,
groups of people and barking dogs with high volume of
noise. In circumstances of high stress, they showed self
mutilation behavior. At the time this paper was written,
they attended a school for special education and showed
good interpersonal relationships. They did not use any
medications to reduce the characteristic symptoms of
FXS.
Similar conditions were observed in members of the
maternal family of the twins. All the collected data for
the construction of a diagnostic genealogy were based
solely on the reports of the twins’ mother, but they seem
to a priori corroborate the behavior and characteristics
seen in FXS. In the descriptive genealogy of this family,
the maternal grandfather had behavior typical of FXS
and was very similar to the twins, suggesting that he
could be the bearer of a pre-mutation FMR1 gene. If this
is true, then 100% of the daughters of this carrier would
carry a pre-mutation for the FMR1 gene. Consequently,
some members of the third generation could be affected
by the fragile X syndrome. Of the 8 daughters of this
carrier who generated grandsons, 6 seem have had de-
scendants with this same anomaly. It was also verified
that all possible female carriers of the pre-mutation in
this family showed premature ovarian insufficiency, a
circumstance that results in precocious menopause.
During the external physical examination of the pa-
tients, it was observed that they had a long face and
prominent ears. In the intrabucal examination, one twin
cooperated for a short period of time, and it was ob-
served that he possessed macroglossia, mandible prog-
nathism, ogival palate, top bite, a normal aspect of mu-

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cosa, many teeth with cavities and a fracture of the me-
sial angle of element 21 caused by trauma. Curiously,
the same problem was observed in his brother (Figure
2).
Because of the limited capacity for cooperation by the
patients, the professional team opted to perform the den-
tal treatment under intravenous sedation. The patients
had been evaluated by the medical anesthetist and, after
detailed anamnesis, a routine physical examination of
both twins, the patients were considered healthy enough
to submit to such a procedure.
First, pre-sedation using midazolan maleate (Dor-
monid®, Roche, São Paulo, Brazil) via the nose (0,5
mg/kg) was administered. After 20 minutes, intravenous
intubation was carried out to maintain the venous access
and to apply a 5% isotonic glucose solution for replace-
ment. To keep the oral cavity dry and to prevent cardiac
arrest, oxygen and atropinization was adapted to be de-
livered via the nasal cavity. For sedation, propofol
(Diprivan®, Astra Zeneca of Brazil Ltda., São Paulo,
Brazil) and fentanyl citrate (Fentanil®, Pharmaceutical
Janssen-Cilag, São Paulo, Brazil) were continuously
infused.
During the operation, the cardio-respiratory condition
of the patients was monitored by an oximeter and elec-
trocardiography. A defibrillator device was available
during the whole procedure for use in case of cardiac
fibrillation by the patients.
For the dental procedures, photopolymerized resin was
used to restore the anterior teeth, amalgam in the poste-
rior teeth and exodontia of elements that had a doubtful
diagnosis (Figure 3). After the dental treatment, a re-
covery period was initiated. The postoperative recom-
mendations to the parents about diet and the ingestion of
antihemetics and analgesics were made, as well as in-
structions regarding correct oral hygiene, diet and the
importance of regular visits to the clinic for dental
maintenance and the oral health of the patients.
3. DISCUSSION
The twins’ behavior was observed with special interest,
due to the presence of some pertinent FXS symptoms
such as hyperactivity, poor vision, problems with speech,
anxiety, sharpened memory, a sense of humor, the ca-
pacity for imitation and situations of panic and violence.
Such behavior is described by some researchers as typi-
cal of individuals with the fragile X syndrome [20].
Treatments for any individual with fragile X syn-
drome is only efficient when combined with therapeutic
counseling, special education and medications in accor-
dance with the special needs of each patient. The relative
aspects of the behavior observed in the described pa-
tients must be considered as genuine symptoms as they
do not use, until now, any medications or participate in
specific therapies to limit the psychopathologic symp-
toms related to this condition.
In the pre-pubertal phase of development, the phe-
noltypic characteristics of patients carrying the fragile X
syndrome do not always show the condition and are
therefore not easy to identify [2]. Although the twins
descrybed in our study fall into this category, it was still
possible to observe the extended face and large ears,
corroborating the clinical findings published previously
[17].
The hypoplasia of dental enamel is described as an
important fact and related to the fragile X syndrome [15,
16], but it was not possible to correlate such facts in our
clinical case.
Intravenous sedation was selected to help with the
dental intervention of the patients, as it had results that
were appropriate for the treatment. This facilitated the
accomplishment of the dental procedures and improved
the quality of the treatment as the twins had a limited
ability to cooperate. It was possible also to reduce the
anxiety provide greater comfort to the patients [19].
Figure 2. Intra-oral view of one patient.
Figure 3. Completed dental treatment of the same patient.

F. M. Meira et al. / Health 2 (2010) 1199-1203
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The timing of dental treatment for an individual with
fragile X syndrome must be designed for each specific
case. The severity of mental retardation and the level of
potential cooperation are factors that can compromise
the treatment success. In situations that necessitate ex-
treme measures, these must be opted for even if it means
intravenous sedation or general anesthesia. It is interest-
ing to observe and identify the stimuli that can cause
positive or negative reactions in patients, initiating a
patient into a plan of treatment with individually appro-
priate and complete dental procedures [17,19].
The approach to these patients should always occur in
a multidisciplinary manner, with the participation of
anesthetist, cardiologist, psychiatrist, speech therapist,
physiotherapist and psychologist.
The greatest difficulty in the treatment of these indi-
viduals is the presence of mental disability. In these
cases autistic demonstrations, aggressiveness or anxiety
require specific care because the patient might need
medications. Thus, the patient’s physician should always
be consulted regarding medications in order to avoid
possible interaction with drugs used in the dental treat-
ments. In a similar manner, patients with heart disease,
which is characteristics of the syndrome, should be
evaluated carefully and the possibility of using antibiotic
prophylaxis for dental interventions that might release
bacteria must be considered.
4. CONCLUSIONS
● This paper provides information regarding the charac-
teristic manifestations of Fragile X syndrome not only
aided in the handling of the patients but also enabled us
to develop clinical programs to promote and maintain
oral health using individualized and specific dental pro-
cedures.
● The course of dental treatment in an individual af-
fected by FXS must be designed specifically in each
case as it is necessary to be aware of the implications
that might interfere with normal dental practices.
● The severity of mental retardation and the degree of
behavioral problems are factors that can compromise the
success of dental treatment. In situations where it is nec-
essary to use auxiliary methods, the completion of the
dental procedure dental might require intravenous seda-
tion techniques or even general anesthesia.
● In the present study, the twins exhibited mental re-
tardation and a certain lack of cooperation. Nevertheless,
since both exhibited only carious lesions and a fracture
of the incisor, treatment under sedation was planned and
conducted out of a hospital unit.
● The identification of individuals affected by Fragile
X syndrome, through accurate diagnosis, allows the
families of these patients to investigate and evaluate
the risks of transmission of this genetic abnormality.
Through appropriate genetic counseling it is possible to
identify other relatives who are at risk of having inher-
ited the altered gene FMR1 and thus make it possible to
identify family members that might be pre-mutation car-
riers before it is transmitted as a full mutation to their
offspring.
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