Noonan syndrome is a congenital, common, hereditary disorder. Facial dysmorphism, growth retardation, and various heart defects are typical clinical features. In patients with minor cardiac pathology, life expectancy is normal. We report a case of renal transplant in a pediatric patient with Noonan syndrome that ended with death of the patient. Our patient presented with unexpected and refractory postoperative neurological com­plications that were unresponsive to intensive therapy, and the patient died because of secondary complications.

Key words : Anesthesia, Complication, End-stage renal disease, Genetics

Introduction

Noonan syndrome is a genetically heterogeneous, congenital, and developmental disorder characterized by dysmorphic facial features, short stature, and a wide spectrum of congenital heart and other defects.^1-3 The estimated incidence of Noonan syndrome is 1 in 1000 to 2500 live births, and the syndrome equally affects both sexes. A gene for Noonan syndrome has been mapped to chromosome number 12. Noonan syndrome may be accompanied by varied skeletal, neurological, genitourinary, hematologic, or dermatologic findings.^1-4

We present a case report of a 4-year-old boy with end-stage renal disease secondary to vesicoureteral reflux and Noonan syndrome who died after renal transplant.

Case Report

A 4-year-old boy with a clinical diagnosis of Noonan syndrome and end-stage renal disease was scheduled for renal transplant from his mother. The patient had Noonan syndrome with typical facial dysmorphism, low growth percentile, and hyper­trophic cardiomyopathy. He had no clinically important skeletal deformity, Mallampati score class 2, and mouth opening was 4 cm. The patient had no findings of cardiac decompensation and his neurological condition was normal. He also had α-thalassemia, and hemoglobin level was 7.1 g/dL after transfusion of 150 mL red blood cells. The serum electrolytes, glucose level, organ function tests, coagulation profile, and platelet level were normal. The preoperative echocardiography revealed nonobstructive hypertrophic cardiomyopathy. None of his family members had characteristics of Noonan syndrome.

After 8 hours without food or drink, he was premedicated intravenously with 2 mg midazolam and taken to the operating room. Standard invasive monitoring was performed with 5-lead electro­cardiogram, radial artery catheter, pulse oximeter, left subclavian central venous catheter, and esophageal heat probe. Antibiotic prophylaxis (ampicillin [50 mg/kg] and gentamicin [2 mg/kg]) was administered 30 minutes before induction of anesthesia. The first measurement of blood pressure was 175/95 mm Hg. After administration of fentanyl and midazolam, the blood pressure decreased to 135/80 mm Hg. Anesthesia induction was performed with ketamine (1 mg/kg) and atracurium (0.4 mg/kg), and the trachea was intubated with a 4.5-mm cuffed endotracheal tube. Anesthesia was main­tained with sevoflurane (1-1.5 minimum alveolar concentration) in a mixture of 50% oxygen and 50% air and intravenous infusion of remifentanil (0.05 μg/kg/min). According to the institutional routine protocol, a bolus of methylprednisolone (1 mg/kg) and infusion of basiliximab (1 mg/kg during 1 hour) were administered at the induction of anesthesia, and mannitol (0.5 g/kg) and furosemide (1 mg/kg) were given intravenously during the vascular anastomosis. After an uneventful and successful operation, the patient was extubated in the operating room and he was transferred to the surgical intensive care unit for hemodynamic and neurological monitoring. The surgery time was 270 min, and bleeding during surgery was 100 mL.

After an uneventful early postoperative course, he developed severe hypertension (195/115 mm Hg) and a generalized tonic-clonic seizure at post­operative hour 14. He was given empiric anti­hypertensive (calcium channel blockers) and antiepileptic drugs (phenytoin). The serum sodium level was 119 mg/dL, and he was reintubated because of decreased level of consciousness.

During the first 48 hours after surgery, his convulsions repeated several times, and he was treated with sodium and erythrocyte replacement. Magnetic resonance imaging (MRI) scan revealed intracranial pressure and intracranial edema. On the second postoperative day, decompressive craniectomy and external ventricular drainage were performed. In the follow-up MRI, intracranial hemorrhage and ischemic lesions were seen.

On the following day, the patient’s consciousness and clinical condition did not show any improve­ment. He had a tracheotomy performed, and he developed various infections. He remained in the intensive care unit until he died at 4 months after surgery secondary to severe septic shock and multiorgan failure syndrome. However, his cardiac and renal functions did not deteriorate during the 4 postoperative months.

Discussion

Noonan syndrome, first reported by J.A. Noonan in 1963, is a clinical disorder with autosomal dominant inheritance and sporadic occurrence. The clinical presentation of Noonan syndrome is variable. The affected cases may have different clinical features such as typical facial properties (hypertelorism, proptosis, micrognathia, down-slanting palpebral fissures, and low posterior hair line), congenital heart defects (pulmonary stenosis, hypertrophic cardiomyopathy, and atrial septal defects), short stature, webbed neck, chest or skeletal deformities, undescended testes, mild intellectual disability, and hematologic anomalies (clotting defects and myelo­proliferative disorders).^1-5 The clinical diagnosis of Noonan syndrome can be made using van der Burgt6 criteria. Our patient satisfied these criteria including facial features, growth retardation, and cardiac dysfunction (hypertrophic cardio­myopathy). Difficult airway treatment and mechanical ventilation due to facial dysmorphism, webbed neck, and vertebral and thoracic anomalies were described in previous reports.^2,7 Endotracheal intubation and mechanical ventilation were performed in our patient without any difficulty. Our patient was known to have heart dysfunction and his cardiac condition could have been a risk for anesthesia. To avoid cardiac decompensation, measures were taken to prevent acute changes in systemic vascular resistance, heart rate, and contractility.

Genitourinary anomalies are detected in 11% patients with Noonan syndrome including renal pelvic dilation, renal hypoplasia or ectopia, and cryptorchidism. Fertility may be normal or diminished. Undescended testes in male patients can occur in 77% patients.^1,8,9 Our patient had end-stage renal disease due to vesicoureteral reflux since age 1 year. He had received peritoneal dialysis initially, and he was treated with hemodialysis for the 6 months before transplant.

Severe psychological or neurological problems are not common in Noonan syndrome. Minimal mental or motor retardation may occur. Partial hearing loss, speech disorders, and visual problems may be observed. Recurrent convulsions may be observed in 13% patients.^1,8,10 The most important cause of poor outcome in our patient was unexpected development of neurological complications. Early after surgery, he had stable cardiac, respiratory, and neurological condition, and renal graft function was excellent. However, he had sudden tonic-clonic seizures at 14 hours after surgery. An increase in intracranial pressure followed by ischemic and hemorrhagic complications were the main reasons for the deterioration of the patient. The early seizures may have been due to electrolyte imbalance. The patient’s urinary output was high on the first postoperative day (10 mL/kg/h). This marked diuresis probably was the reason for the electrolyte imbalance. He subsequently developed serious infections and died. No cardiac problems or complications related to the transplanted kidney was observed until multiorgan failure developed from sepsis at the terminal stage.

In conclusion, Noonan syndrome can affect multiple organs or systems and the anesthesiologist may confront various challenges. The most frequent difficulties are airway problems, cardiac anomalies, musculoskeletal anomalies, and bleeding diathesis. Although neurological complications are rare, they are important because they can cause severe morbidity and mortality. Potential susceptibility of these patients should be considered during major surgery, especially when rapid fluid shifts, electrolyte imbalance, or other neurological problems may occur. Poor outcomes can be prevented with increased awareness of these complications and careful patient evaluation. Careful preoperative assessment may help anesthesiologists prepare for potential problems during anesthesia.

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