General anesthesia and fragile X syndrome: report of a case.
ABSTRACT A case report of an 11-year-old Caucasian boy with the fragile X syndrome is presented. The fragile X syndrome is a form of X-linked mental retardation with a connective tissue component that involves mitral valve prolapse. Antibiotic prophylaxis, electrocardiographic abnormalities, and special anesthetic management considerations are elements of treating patients with fragile X syndrome. The patient received morphine sulfate and scopolamine as a preoperative premedication. Ketamine was also administered intramuscularly prior to induction to gaseous anesthetic. Pancuronium was used to facilitate nasotracheal intubation. A wandering atrial pacemaker and progressive hypocapnia, both of which were managed without complication, were the only problems encountered in the anesthetic procedure.
- American Journal of Medical Genetics 02/1984; 17(1):5-94.
- [show abstract] [hide abstract]
ABSTRACT: Eleven cytogenetically documented patients with the fragile X syndrome were evaluated for hyperextensibility of the finger joints and the presence of other manifestations of connective tissue dysfunction. All of the patients had hyperextensibility of several finger joints and many had features such as flat feet, highly arched palate and the ability to voluntarily dislocate finger joints. These traits, particularly hyperextensibility of the joints, are a useful aid in the clinical diagnosis of the fragile X syndrome.American Journal of Medical Genetics 02/1984; 17(1):111-21.
- Special Care in Dentistry 01/1984; 4(4):158-9.
General Anesthesia and Fragile X Syndrome:
Report of a Case
Paul S. Casamassimo, D.D.S., M.S.,* William B. Mcllvaine, M.D., C.M., F.R.C.P. (C),t
Randi Hagerman, M.D.,t
*Department of Growth and Development, tDepartment of Anesthesia, tDepartment of Pediatrics,
University of Colorado Health Sciences Center, School of Dentistry, Denver; Sewall Rehabilitation
Center, and The Child Development Unit, The Children's Hospital, Denver, 'Dental Department, Ridge
Regional Center, Wheatridge, Colorado
Iand W. Craig Shellhart, D.D.S.*§
A case report of an 11-year-old Caucasian boy with the fragile X syndrome is presented. The
fragile X syndrome is a form of X-linked mental retardation with a connective tissue component
that involves mitral valve prolapse. Antibiotic prophylaxis, electrocardiographic abnormalities,
and special anesthetic management considerations are elements of treating patients with
fragile X syndrome. The patient received morphine sulfate and scopolamine as a preoperative
premedication. Ketamine was also administered intramuscularly prior to induction to gaseous
anesthetic. Pancuronium was used to facilitate nasotracheal intubation. A wandering atrial
pacemaker and progressive hypocapnia, both of which were managed without complication,
were the only problems encountered in the anesthetic procedure.
The fragile X syndrome [fra(X)] is a relatively
common cause of familial mental retardation as-
sociated with a fragile site on the long arm of the X
chromosome. The estimated incidence approaches
1 in 1000 live male births and the syndrome may be
responsible forapproximately50% ofcases involving
X-linked mental retardation.
Clinical findings in fra(X) include large or prominent
ears and macroorchidism (Fig. 1). Recently, possible
connective tissue problems including hyperextensi-
ble joints, high arched palate, pectus excavatum de-
formity, mitral valve prolapse (MVP), and mild aortic
root dilation5 have been described in a significant
percentage of fra(X) patients.36 Although approxi-
mately 80% of males with fra(X) demonstrate MVP
on examination and echocardiogram, this cardiac
abnormality has not been associated with chest pain,
fainting, or palpitations.46
Accepted for publication March 13, 1985.
Address reprint requests to Dr. Paul Casamassimo, Chairman,
Department of Growth & Development, School of Dentistry,
UCHSC, 4200 E. 9th Ave., Box.C284, Denver, CO 80262.
This report describes treatment of an 11-year-old
boy with fra(X) who received general anesthesia for
dental caries. A review of both medical and dental
literature failed to reveal any information regarding
the risks of management of the patient with fra(X)
under general anesthesia.
Presenting Problems and History
The patient, an 11-year-old Caucasian male with a
diagnosis of the fragile X syndrome including mental
retardation, was referred to our institution for treat-
ment of dental caries. Attempts at treatment in a
dental office had failed due to behavioral problems.
Because of the boy's age and size, anticipated treat-
ment needs and lack ofcooperation, dentaltreatment
under general anesthesia was attempted at a small
rural hospital. The general anesthetic procedure
using mask induction with halothane was terminated
prematurely due to a superventricular tachycardia of
over 200 beats/minute. The parents later reported
that a grandfather had also experienced difficulty with
a dentally related anesthetic. This was described as
an outpatient intravenous anesthetic administered in
a dentist's office to which the grandfather was re-
ported to have reacted badly. The parents could not
provide any more detail on the drug or the type or
extent of reaction. This history suggested malignant
and Laboratory Data
Physical examination demonstrated an 11-year,
5-month-old Caucasian male weighing 59 pounds
(3rd percentile) and standing 56 and 3/4 inches (40th
percentile). His face was thin and long with prominent
ears and a narrow dental arch. Examination of his
chest revealed normal precordium and a soft early
systolic click. Genitalia were prepubertal in develop-
ment with a large scrotal sac and a bilateral testicular
volume of 12 ml. Bilateral hydrocoele was also pre-
sent. Extremities demonstrated decreased tone with
hyperextensible finger joints bilaterally. A simian
crease was found in the left palm. Chest radiograph
and electrocardiogram were normal, but echocar-
diography revealed a late systolic prolapse of the
mitral valve and an aortic root diameter of 22 mm
(upper limit of normal for age).
Hematological and urine testing were within nor-
mal limits. A platelet halothane bioassay7 for malig-
nant hyperthermia was normal.
Fig. 1-Clinical findings in fragile Xsyndrome. (A) FragileX boy
demonstrating large prominent ears; (B) macroor-
chidism in postpubertal fra(X) male.
Course of Treatment
The child was hospitalized and received the usual
preoperative preparation, including anesthesia con-
sultation. Due to the child's retardation and be-
havioral problems, preoperative premedication con-
sisting of morphine sulfate (0.15 mg/kg) and
scopolamine (0.4 mg/kg) was administered in-
tramuscularly prior to leaving his room. In addition, he
received prophylaxis with penicillin for MVP accord-
ing to the guidelines of the American Heart Associa-
Ketamine (5 mg/kg) was administered intramuscu-
larly in the operating room to manage the child's
uncooperativeness prior to induction. Once asleep,
monitoring was established with EKG (lead 11), BP
cuff, precordial stethoscope, and axillary tempera-
ture probe. Inspired 02 concentration and end-tidal
C02 were also monitored. After an intravenous can-
nula was inserted, pancuronium (0.15 mg/kg) was
given in facilitate nasotracheal intubation.
During the procedure, the patient remained stable
in sinus rhythm. There were brief episodes of a wan-
dering atrial pacemaker as manifested by a change in
p-wave morphology. Progressive hypocapnia, in-
duced by an increase in controlled minute ventilation,
resulted in a shortening of the P-R interval and de-
velopment of a nodal rhythm at the same rate. Be-
cause the patient was hemodynamically stable, no
therapy was required except to allow the PacO2 to
return to normal. The remainder of the case pro-
Recovery was uneventful and the patient was dis-
charged to his parents the day after the operation
with appropriate antibiotics to complete the
Two subsequent anesthetics for this patient on an
outpatient basis for treatment of his bilateral hy-
drocoeles were equally uneventful, using rectal
methohexital (20 mg/kg) for induction and caudal
analgesia for postoperative pain relief.
The significance of this case relates to the high inci-
dence of mitral valve prolapse in fra(X) patients. Mitral
valve prolapse accounts for a large portion of hospitali-
zations for subacute bacterial endocarditis (SBE).7 In
addition, MVP can lead to cardiac arrhythmias which
can complicate anesthetic monitoring.
Few dentists have a familiarity with the fra(X) syn-
drome. Many fra(X) patients have not been identified
because of the cost of chromosomal analysis. Esti-
mates suggest that the fragile X syndrome may be
second only to Down's syndrome as a cause of
chromosomally related retardation. These factors,
combined with the high incidence of MVP and the
need for echocardiography for identification in many
cases, puts these patients at risk for SBE. The dentist
treating the mentally retarded patient with no clear
diagnosis should investigate further for cardiac prob-
lems, especially when clinical examination suggests
This case is also interesting for its mimicking of
malignant hyperthermia (MH). The tachycardia noted
at the child's first abortive general anesthetic is com-
mon in MH.8 The family history of an anesthetic prob-
lem coupled with the history of tachycardia made
testing obligatory. Although the platelet-halothar.e
bioassay is considered accurate, a temperature
probe was used for the patient monitoring in this
procedure. The tachycardia and EKG abnormalities
are attributable to MVP.
A final set of considerations forthis anesthetic case
relate to the physical problems of fra(X). The palate
form may be abnormal and this could complicate
mask fit and intubation. Joint laxity and large testicu-
lar volume make positioning of extremities important
to avoid dislocation or gonadal compression. Un-
cooperative behavior suggestive of autism makes
strong preoperative medication a consideration.
Ketamine was used in this case and proved safe and
Herbst DS and Miller JR: Non-specific X-linked mental retarda-
tion. II. The frequency in British Columbia. Am J Med Genet
2. Opitz JM and Sutherland GR: Conference report: International
workshop on the fragile X and X-linked mental retardation. Am J
Med Genet 17:5-94, 1984.
3. Hagerman RJ, Van Housen K, Smith ACM, McGavran L: Con-
sideration of connective tissue dysfunction in the fragile X syn-
drome. Am J Med Genet 17:111-121, 1984.
4. Hagerman R, Smith ACM, Mariner R: Clinical features of the
fragile X syndrome. In The Fragile X Syndrome: Diagnosis,
Biochemistry and Intervention, Hagerman RJ, McBogg P
(Eds.), Spectra Publishing Co, Dillon, 1983, pp. 17-53.
5. Synhorst D and Hagerman RJ: Mitral valve prolapse in the
fragile X syndrome. Poster presentation. March of Dimes Birth
Defects Meeting, Denver, Colorado, June 17, 1984.
6. Solomons CC and Masson NC: Platelet model for halothane-
induced effects on nucleotide metabolism applied to malignant
hyperthermia. Acta Anaesthesiol Scand 28:185-190, 1984.
7. Kerpen SJ, Kerpen HO, Sachs SA: Mitral valve prolapse: A
significant cardiac defect in the development of infective en-
docarditis. Spec Care Dentist 4:158-159, 1984.
8. Long-Ren Lin R, Nguyen HH, Sonnenberg E, Gubitosa L:
Malignant hyperthermia: Case report. Pediatr Dentist 4:341-