General anesthesia or anticholinesterase reversal of neuromuscular block for patients with neuromuscular disease may aggravate muscular weakness or induce myotonic episodes [1]. If halothane is used with succinylcholine, the increased jaw muscle tone in some normal subjects may be confused with true abnormal trismus [2]. In half of trismus patients, rigidity is associated with biopsy-confirmed malignant hyperthermia syndrome (MHS) [3,4]. Generalized rigidity may also be a sign of malignant hyperthermia (MH) in the absence of succinylcholine administration. Classically, generalized rigidity is late in onset and associated with a fulminant episode of MH [5,6]. We report a patient with Smith-Lemli-Opitz syndrome who exhibited a sudden onset of generalized muscle rigidity after halothane N2 O-O2 induction of anesthesia without succinylcholine and who did not have confirmed MH. Case Report A 4-year-old male with Smith-Lemli-Opitz syndrome and ptosis was scheduled for a fascia lata sling brow suspension. Past history included prematurity and developmental delay. Prior surgery included orchiopexy and posterior spinal fusion for scoliosis. Anesthesia for orchiopexy included thiopental, vecuronium, and halothane in nitrous oxide-oxygen (N2 O-O2) and single-dose caudal block with 8 mL of 0.25% bupivacaine. A few minutes later, his legs were noted to be stiffer than preoperatively. The muscles relaxed soon after converting to a narcotic-relaxant technique using alfentanyl, pancuronium, and N2 O-O2. His highest temperature was 38 degrees C rectally. Blood gas measurements revealed pH at 7.40, Pa CO2 44 mm Hg, and Pa O2 209 mm Hg. Postoperative creatine kinase (CK) level was 1244 IU/L (normal 35-232 units). Recovery was uneventful. Anesthesia for scoliosis surgery included sufentanil, midazolam, pancuronium, air, and oxygen. Isoflurane was added briefly; when rectal temperature increased to 39 degrees C, isoflurane was discontinued and rectal temperature soon decreased to < 38 degrees C. For the ptosis repair, preoperative evaluation revealed weight below the fifth percentile at 12.4 kg. Clinical evaluation revealed micrognathia, microcephaly, and stiffness of the extremities. Anesthesia induction was initiated with halothane in N2 O-O2. Endotracheal intubation was performed without the use of muscle relaxant. Within a few minutes, the patient developed generalized muscle rigidity associated with difficult ventilation. The chest movement and breath sounds were diminished in spite of high inspiratory pressure and rapid respiratory rate indicating severe decrease in compliance of the chest wall. Atracurium and fentanyl, were given intravenously (IV), and halothane was discontinued with no immediate improvement in rigidity or ventilation. Oxygen saturation decreased to 95% despite vigorous ventilation with a FIO2 of 1.0. End-tidal carbon dioxide was 93 mm Hg (PET CO2). Arterial blood gas measurements confirmed hypercarbia (105 mm Hg) and respiratory acidosis, pH at 7.05. Since he was not improving after the discontinuation of halothane, fentanyl and atracurium were reversed with naloxone and edrophonium with atropine. Fortunately, the ophthalmologist was able to complete the surgery before the patient emerged from anesthesia. Thirty minutes after discontinuing all anesthetics, the patient was able to breathe spontaneously, in spite of persistent but diminishing generalized rigidity. A CK of 117 IU/L was present in the blood specimen drawn during the episode of rigidity. He was in his usual state of health when discharged to his home 2 h after awakening. At the time of discharge, he still demonstrated limited passive and active motion of the extremities which was unchanged from preoperative examination. Discussion The Smith-Lemli-Optiz syndrome is characterized by mental, motor, and growth delay, microcephalus, elfin facies, hypoplasia of the external genitalia, and syndactyly of the toes. Prognosis is poor, with death frequently occurring in infancy due to pulmonary infection or congenital heart defect [7]. The patient was unique in that he exhibited dramatic rigidity related to halothane. A major concern during anesthesia associated with muscle rigidity is MH [5,6]. Although this patient developed muscle rigidity, his CK values were never increased to levels generally associated with MH. MH occurs more commonly in patients with strabismus and ptosis and in Duchenne's muscular dystrophy than in the general population [8]. MHS describes susceptibility to MH, not the acute episode itself [9]. During the ptosis procedure, the rigidity was more severe and widespread than during the orchiopexy, possibly because IV anesthetics including vecuronium, were used to facilitate induction and a smaller dose of halothane was used during the previous induction. Rigidity developed without the use of succinylcholine each time. Other anesthetics were used in addition to halothane during the orchipexy. Rigidity did not develop during the spinal fusion, but halothane was not used. Thus rigidity developed only when halothane in N2 O-O2 was the only anesthetic used. This indicates that this episode may have been a direct reaction to halothane. Review of literature revealed one report in the Japanese literature of a child with Smith-Lemli-Opitz syndrome and seizure disorder who exhibited rigidity after halothane in N2 O-O2 and succinylcholine for induction of anesthesia with bupivacaine caudal block in preparation for bilateral orchipexy and bilateral inguinal herniorrhaphy [10]. He was not rigid with halothane alone and was not difficult to ventilate. He had tightness of the jaw and became hypothermic intraoperatively. The surgeon noted some tightness of the abdomen and thigh muscles. Arterial blood gases and serum electrolyte levels measured intraoperatively revealed no abnormality other than hypocarbia. Postoperative CK was 762 IU/L and lactate dehydrogenase, glutamic-oxaloacetic transminase, and glutamic-pyruvic transaminase levels were increased. He tolerated anesthesia for skin grafting with enflurane in N2 O-O2 with vercuronium and caudal block with bupivacaine without developing rigidity and without increase in postoperative enzymes. Temperature variability noted during and after both procedures was though to be secondary to central autoregulatory dysfunction [10]. The comparison of our patient and the Japanese patient with Smith-Lemli-Opitz syndrome with the classic MH patients is depict in Table 1[10]. Our patient's arterial blood gas measurements were not indicative of MH. The metabolic component of the acidosis was milder than that seen in MH [6]. The characteristics of oxygen desaturation and hypercarbia may fit MH, but the signs were not typical, nor was the CK level markedly increased postoperatively. The hypoxia and hypercarbia seemed attributable to hypoventilation due to generalized rigidity with severely reduced chest wall compliance.Table 1: Comparison of Smith-Lemli-Opitz Syndrome and Classic Malignant HyperthermiaOur patient does not fit the picture of stiff-baby syndrome, or hyperekphexia, in which the response to a startle is exaggerated. The stiffness may be aggravated by narcotics and nitrous oxide. Halothane did not cause rigidity in the patient studied with stiff-baby syndrome, but succinylcholine did not result in normal degrees of skeletal muscle relaxation [11,12]. Based on this episode, we now advise against the use of either succinylcholine or halothane in patients with Smith-Lemli-Opitz syndrome. We thought it may have been safe to use halothane without succinylcholine for induction of anesthesia for the ptosis repair. The previous episode of rigidity was not known to be caused by halothane because it seemed to involve the legs and not the upper body. The rigidity was reversed easily by discontinuing halothane and converting to nitrous oxide-narcotic technique. Also, IV access may have been difficult to establish in this patient. The narcotic-relaxant technique was well tolerated and may be safe to use in other patients with this condition. Epidural (caudal) block using 0.25% bupivacaine was used safely in the Japanese patient and may be used safely in other patients with Smith-Lemli-Opitz syndrome. Careful monitoring for early signs of muscle rigidity and temperature increase must be performed in any patient, and the anesthetic technique modified or abandoned should these occur. Dantrolene, the drug of choice in the treatment of MH, may be therapeutic in alleviating the rigidity and should be tried if the rigidity becomes prolonged or severe [13]. It might have been effective in the treatment of this patient but was not given because we did not appreciate its effectiveness in non-MHS rigidity. It is possible that this patient could be MHS, but it cannot be diagnosed without a muscle biopsy, since a fulminant episode of MH did not occur. Postoperative observation for signs of MH for at least 6 h is advisable. Repeat CK level should have been checked as well as serum electrolytes, arterial blood gases, and urine for myoglobin.