a 7 year - old , 113 cm , 17 kg , female patient with tooth decay presented for general anesthesia for tooth conservation day surgery because outpatient treatment was not possible due to her lack of cooperation .
her medical history showed that she had been delivered normally after 39 weeks of gestation , weighing 2.8 kg . at birth ,
seven months after birth , pediatric parent visits were made due to a general developmental delay , microcephaly , and sleep disorder .
fourteen months after birth , brain mri ( magnetic resonance imaging ) was performed , which revealed no abnormalities . however , a chromosomal study showed a deficiency of chromosome 15 at q11.2-q13 , and a fish ( fluorescence in situ hybridization ) test confirmed angelman syndrome ( fig .
, spasms began to occur , which became severe when the sleep disorder happened frequently . at approximately age 4 , general myoclonus epilepsy occurred .
thereafter , she took valproic acid 125 mg , in divided into two doses two times per day , and experienced convulsion at 3 to 5 months intervals .
an sms ( social maturity scale ) test , which was taken in the 30 month after birth , revealed severe intellectual retardation with a social age of 0.32 .
regarding motor development , she was equivalent to a 4 - 7 month old for the gross motor , 1 - 4 month old for the fine motor , and 1 - 2 months old for language development .
the neurological test revealed that the child 's flexor in the arms and legs was hyper - tensed , her skeletal muscle was not fully developed , and she showed slight dystonic tremor .
the morphological characteristics were microcephaly and hypoplasia of the maxillary bones . in the anteroom for day surgery ,
the child patient was uncooperative with the medical staff and would not leave her parent .
the girl could not walk , and she was nestling in her parent 's arms , speaking incomprehensible words and making infelicitous laughs .
the blood test before the operation revealed a hemoglobin level of 11.8 g / dl , which was slightly low .
. in the anteroom for day surgery , an intravenous route was secured with the assistance of the surgical staff and parent .
for the induction of general anesthesia , midazolam 2 mg instead of the ketamine commonly used in the hospital was administered with concern over seizure .
however , it failed to sedate her and another 2 mg was administrated , which had no effects .
a decision was made not to use different kinds of intravenous anesthetics because of the concern about the delay in awakening and restoration from anesthesia .
the girl was carried into the operating room ( or ) in her parent 's arms .
the vital signs immediately after entering the or revealed a blood pressure , pulse rate and oxygen saturation of 110/60 mmhg , at 110/min and 96% , respectively .
sevoflurane and 100% oxygen were employed to induce anesthesia , and after administering rocuronium bromide 10 mg as a muscle relaxant , mask ventilation began and there was no difficulty in ventilation . after confirming full muscle relaxation ,
an orotracheal intubation was performed with a cuffed endotracheal tube ( 4.5 mm ) without problems .
expecting trouble in endotracheal intubation , oropharyngeal intubation was first performed and the operation proceeded while maintaining orotracheal intubation at the consent of the pediatric dentistry department . by regulating the oxygen to air ratio to set a fraction of inspired oxygen ( fio2 ) at 0.5 , controlled respiration was performed to maintain a partial carbon dioxide pressure in expiration of 30 - 35 mmhg while maintaining anesthesia with sevoflurane 3 vol% . during surgery , the blood pressure and pulse oximetry was stable at 100 - 110/60 - 70 mmhg and 99 - 100% , respectively .
pyridostigmine 5 mg and glycopyrrolate 0.15 mg were then administrated to reverse muscle relaxant . before extubation ,
the train of four ( tof ) stimuli was measured to indicate 3 and the endotracheal tube was removed after confirming that the muscle function had been fully restored .
the total length of time for tooth conservation surgery was 100 minutes , and the length of anesthesia was 125 minutes . in the postanesthetic recovery unit , the patient showed stable breathing and vital signs and her motion functions were checked after reaching consciousness .
the next day 's follow - up phone call also confirmed her good general condition without significant complications .
angelman syndrome ( as ) is a congenital disorder showing a variety of clinic manifestations due to a partial deficit on the paired chromosome 15 .
the prevalence of as is one in 10,000 - 40,000 of the population and its clinical characteristics are so diverse that a diagnosis of as rests on a combination of molecular genetic testing and/or cytogenetic analysis .
70% of as patients have the loss of the maternally contributed region of chromosome 15q11 - 13 , while 15% of as have uniparental disomy coming from a paternal contribution .
60% of the paternal deletion in the chromosome region 15q11 - 13 may cause prader - willi syndrome ( pws ) .
the characteristic symptoms of pws can be differentiated from those of as by the clinical features , by hypotonicity and early obesity in infancy , mental retardation and hypogonadsm .
genetic imprinting refers to the accentuation or activation of genes that can be expressed in a parent - of - origin - specific manner . for the remaining 20% of as cases , no genetic malformation is manifested but patients have a mutation of the ube3a gene and show fewer abnormalities in the electroencephalographic ( eeg ) findings and a smaller number of spasms .
the clinic features of a genetic mutation and deficiency vary according to the gene expressions of rb3 , which is critical in the genetic coding of the 3 subunit of the gaba - areceptor .
many drugs acting on the central nervous system , such as anti - anxiety medication , sedative - hypnotics , general anesthetics , anti - seizure drugs , etc . are considered to acton the gaba receptor .
a study on genetically manipulated mice of aminoacid mutated from the 3 subunit of the gaba receptor showed that reduced effects of propofol and etomidate .
homanics et al .   reported a meaningful decrease in benzodiazepine binding in genetically manipulated mouse models of angelman syndrome . in the present case , midazolam 4 mg
was administered into the vein before surgery to reduce the patient 's anxiety , but she was not sedated .
a change in the distribution of the receptors caused by isoflurane and partly by sevoflurane activates the outer structure of the synapse through osmotic changes in ions .
such a polar change in neuronal cells not only restrains the activity of neuronal cells themselves but also reflect the state of the general anesthetics .
therefore , it is reasonable to minimize or avoid administering an excessive dose of benzodiazepine to patients with this syndrome , and to refrain from using halogenated ethers as an inhalation anesthetic . from a theoretical viewpoint , intravenous anesthesia using a combination of propofol and fentanyl , which are not known to collide with the gaba system , will be safe .
on the other hand , patients with as can show symptoms of separation anxiety due to their severe mental retardation . for child patients who show separation anxiety at general anesthesia for outpatient surgery , securing an intravenous route after admitting the patients into the operating room accompanied by their parents and sedating them with inhalation anesthetics is desirable for reducing the children 's anxiety .
patients with this syndrome usually require general anesthesia for orthopedic surgery for the skeletal system dysfunction or even in a simple operation because they are uncooperative . as may not be detected at birth or during infancy , and is revealed mainly after the age of four , when the characteristic behaviors and signs appear . with several exceptions ,
table 1 shows the consensus criteria of the clinical features in as , enacted in 2005 .
patients with as do not have cardiovascular disorders or arrhythmia as common features but may have bradycardia due to hypertension of the vagus nerves . this phenomenon is noticed mainly during convulsive laughter , which can contribute to severe arrhythmia or ventricular asystole or fainting , resulted from an increase in the intrathoracic pressure and valsalva effect .
the administration of atropine to treat the unexpected arrhythmia during surgery is not always effective .
moreover , the immediate use of cardiac massage and epinephrine should be considered if asystole occurs .
malformations of the skull and facial bones ( microcephaly , mandibular bulging , etc . ) found in patients with as can be a serious hindrance to tracheal intubation
. however , the present case did not experience significant difficulty , and the literature review has not reported any difficulty in tracheal intubation .
however , preparations should be made for any possible contingency when an unexpected malformation is confronted .
many patients with as take medication for hyperactivity and epilepsy . to prevent perioperative epilepsy , it will be wise to keep taking anti - seizure drugs during the operation .
however , it is unclear if all patients with as should take anti - seizure medication as preventive medicine . when choosing anesthetics , drugs that can cause seizure , such as ketamine or enflurane , should be avoided .
peripheral muscular atrophy is another problem that needs to be considered when administrating anesthesia to patients with as .
when it does occur , the sensitivity may increase , and a smaller amount of muscle relaxant than the usual dosage should be applied .
monitoring the level of muscle relaxation is required to ensure the appropriateness in the degree of muscle relaxation during operation and during restoration from muscle relaxation after surgery . in the present case ,
the anesthesia was induced with inhalation anesthetics and maintained with a small dose of muscle relaxant , while there were no added muscle relaxants except those administered before the induction of anesthesia .
tof ( train of four ) stimuli indicated a count of 3 before extubation after surgery .
monitoring of the muscle relaxation of patients is necessary because of the possible risks of seizures and peripheral muscular atrophy . in particular , for outpatient surgery , extra precautions against accidents , such as falls due to muscular atrophy , should be taken after being discharged home .
in addition , preparations should be made for emergencies , such as arrhythmia and ventricular asystole due to the hypertension of the vagus nerves .
the difficulty in securing the respiratory tract in cases with malformations of the facial bones should be anticipated .
in addition , proper attention should be paid to the choice of intravenous anesthetics and their correct dose in an abnormal case of an impairment of the gaba receptors .
 angelman syndrome is characterized by a partial deficit of paired autosomal chromosome 15 , which contains a subunit of the gaba ( gamma - amino butyric acid ) receptor . 
 many drugs that act on the cns ( central nerve system ) during anesthesia are believed to exert their effects via the gaba receptors . 
 we describe the anesthesia of a 7 year - old female patient with angelman syndrome who underwent surgery for dental caries . 
 the basic factors that needed to be considered when administering anesthesia to this patient were epilepsy , significant dominance of the vagal tone , craniofacial abnormalities and peripheral muscular atrophy . 
 inhalational anesthetics ( sevoflurane ) were employed for this patient . 
 the patient had an uneventful peri - operative period and was discharged home on the same day of the operation . 
Case Report
Discussion