Neurosurgical aspects of Noonan syndrome.

PURPOSE: Noonan syndrome (NS) is a rare neurodevelopmental syndrome characterized by dysmorphic features, congenital heart defects, neurodevelopmental delay, and bleeding diathesis. Though rare, several neurosurgical manifestations have been associated with NS, such as Chiari malformation (CM-I), syringomyelia, brain tumors, moyamoya, and craniosynostosis. We describe our experience in treating children with NS and various neurosurgical conditions, and review the current literature on neurosurgical aspects of NS. METHODS: Data were retrospectively collected from the medical records of children with NS who were operated at a tertiary pediatric neurosurgery department, between 2014 and 2021. Inclusion criteria were clinical or genetic diagnosis of NS, age < 18 years at treatment, and need for a neurosurgical intervention of any kind. RESULTS: Five cases fulfilled the inclusion criteria. Two had tumors, one underwent surgical resection. Three had CM-I, syringomyelia, and hydrocephalus, of whom one also had craniosynostosis. Comorbidities included pulmonary stenosis in two patients and hypertrophic cardiomyopathy in one. Three patients had bleeding diathesis, two of them with abnormal coagulation tests. Four patients were treated preoperatively with tranexamic acid, and two with Von Willebrand factor or platelets (1 each). One patient with a clinical bleeding predisposition developed hematomyelia following a syringe-subarachnoid shunt revision. CONCLUSIONS: NS is associated with a spectrum of central nervous system abnormalities, some of which with known etiology, while in others a pathophysiological mechanism has been suggested in the literature. When operating on a child with NS, a meticulous anesthetic, hematologic, and cardiac evaluation should be conducted. Neurosurgical interventions should then be planned accordingly.

Use of a Spinal-Caudal Epidural Technique for Abdominal Surgery in a Newborn With Noonan Syndrome and Severe Hypertrophic Cardiomyopathy.

Features of Noonan syndrome include a distinctive facial appearance, short stature, a broad or webbed neck, congenital heart disease, bleeding problems, skeletal malformations, and developmental delay. Although pulmonary stenosis is most commonly reported, up to 20% of patients have hypertrophic cardiomyopathy (HCM). We report the use of a combined spinal-caudal epidural anesthesia technique during urologic surgery (pyeloplasty) in an 8-week-old infant with Noonan syndrome and HCM. A spinal-caudal epidural technique provides favorable hemodynamic conditions, avoids the need for airway instrumentation, and may serve as an alternative to general anesthesia in these high risk patients.

Kidney Transplantation in a Patient With Noonan Syndrome: A Case Report.

Noonan syndrome (NS) is a congenital genetic abnormality characterized by short stature, delayed onset of puberty, cardiac malformations, and characteristic external malformations. Congenital chromosomal or genetic abnormalities are sometimes associated with carcinomas. Furthermore, they are difficult to manage perioperatively because of multiple complications and mental retardation. The safety of kidney transplantation for patients with NS has not been established. We are reporting the case of a 31-year-old man with NS who received a kidney transplantation after a donor's brain death. He received kidney transplantation safely and was discharged without issues. Kidney transplantation for patients with congenital chromosomal or genetic abnormalities is feasible without serious complications, with a regular follow-up, and psychological support from patients and families.

Noonan syndrome: cochlear implantation in the setting of cochlear nerve deficiency.

BACKGROUND AND AIM: Noonan syndrome (NS) is a congenital disorder characterized by a wide heterogeneity in clinical and genetic features. Hearing loss can frequently occur in NS, although not always mentioned in its diagnostic criteria. We are reporting on a child with an established NS who underwent bilateral cochlear implantation (CI) in the setting of cochlear nerve deficiency. CASE PRESENTATION: We present the case of a child-girl affected by NS. Newborn hearing screening and audiological evaluations reveled an asymmetric sensorineural hearing loss (SNHL), profound at left ear and severe at right ear. Hearing aids were fitted at the age of six months. Brain magnetic resonance imaging showed hypoplastic cochlear nerves. Due to progressive worsening of the hearing thresholds and inappropriate speech development, at the age of 2 years she underwent a left-sided cochlear implantation. Four years later, right ear was also implanted. Six years after the first surgery, a partial extrusion of the electrode array was noticed. Explantation and reimplantation of a new device was performed, adopting a subtotal petrosectomy approach. The patient reached a score of 95% in open-set speech perception tests. CONCLUSIONS: Hearing loss is a frequent finding in patients with NS; however, its nature and severity are very heterogenous. In consideration of the possible progression of SNHL, audiological follow-up in NS patients must be carefully and periodically performed so as to early detect worsening of hearing threshold. If indicated, cochlear implantation should be considered, taking account of audiological and systemic features of this syndrome.

Systematic literature review of lymphatic imaging-guided procedural management of Noonan syndrome.

OBJECTIVES: To assess through literature case analysis how advances in lymphatic imaging, interventional radiology, and lymphatic vascular microsurgery illuminate and improve the lymphatic-flow status in select patients with Noonan syndrome (NS) who have undergone surgical intervention as a part of their comprehensive and individualized treatment plan. Also, we sought to illustrate the spectrum of lymphatic complications that can occur in this patient population when lymphatic flow through abnormal vasculature is surgically disrupted. METHODS: A literature review was performed by searching "Noonan AND Lymphatic AND Imaging" in the PubMed database. Inclusion criteria for this study were (1) diagnosis and clinical description of at least one original patient with NS, (2) imaging figures depicting lymphatic structure and function or a description of lymphatic imaging findings when a figure is not present, and (3) documentation of either lymphatic surgical intervention or lymphatic complications resulting from other procedures. Patient cases were first grouped by documented surgical intervention type, then clinical outcomes and lymphatic imaging results were compared. RESULTS: A total of 18 patient cases from 10 eligible publications were included in our review. Lymphatic imaging findings across all patients included lymphatic vessel dysplasia along with flow disruption (n = 16), thoracic duct malformations (n = 12), dermal lymphatic reflux (n = 7), and dilated lymphatic vessels (n = 4). Lymphovenous anastomosis (n = 4) resulted in rapid improvement of patient symptoms and signs. New-onset lymphatic manifestations noted over 10 to 20 years for two of these patients were chylothorax (n = 1), erysipelas (n = 1), and gradual-onset nonchylous scrotal lymphorrhea (n = 1). Targeted endovascular lymphatic disruption via sclerosis, embolization, or ablation (n = 8) results were mixed depending on the degree of central lymphatic involvement and included resolution of symptoms (n = 1), postoperative abdominal hemorrhage (n = 1), stable condition or minor improvement (n = 5), and death (n = 2). Large lymphatic vessel ligation or accidental incision (n = 6) occurred during thoracotomy (n = 4), scrotoplasty (n = 1), or inguinal lymph node biopsy (n = 1). These resulted in postoperative onset of new-onset regional lymphatic reflux (n = 5), chylothorax (n = 4), death (n = 3), or persistent or unchanged symptoms (n = 1). CONCLUSIONS: Imaging of the central lymphatics enabled characterization of lymphatic developmental features and guided operative management of lymphatic vascular defects in patients with NS. This review of the literature suggests that the surgical preservation or enhancement of central lymphatic return in patients with NS may improve interventional outcomes, whereas the disruption of central lymph flow has significant potential to cause severe postoperative complications and worsening of the patient's clinical condition.

Staged Corrective Surgery for a Patient With Sagittal Malalignment Related to Noonan Syndrome: A Case Report.

CASE: A 20-year-old man with Noonan syndrome had rigid cervical kyphosis caused by cervical myelopathy and thoracic lordosis caused by pulmonary disfunction. Two-staged corrective surgery, which involved initial posterior spinal fusion (PSF) in T2-L2 followed by PSF in C3-T2, had been performed without any complications. The radiographs before surgery and 2 years after surgery showed that cervical lordosis (C2-7) changed form -56° to -29°, and thoracic kyphosis (T5-12) improved from -49° to 10°. CONCLUSION: Initial realignment surgery in the caudal lesion should be better for improving global spinal alignment in patients with rigid spinal deformities at different locations.

Respiratory Failure in Noonan Syndrome Treated by Microsurgical Thoracic Duct-Venous Anastomosis.

Noonan syndrome is a disorder characterized by central and peripheral lymphatic conducting anomalies, leading to chylothorax, chylous ascites, and metabolic derangement. Novel imaging methods, including dynamic contrast magnetic resonance lymphangiography and intranodal lymphangiography, have allowed for increased visualization of lymphatic pathology. Severe pulmonary insufficiency and chylothoraces developed in a 61-year-old man with Noonan syndrome. Dynamic contrast magnetic resonance lymphangiography and intranodal lymphangiography demonstrated central thoracic duct (TD) occlusion. The patient's condition significantly improved after a microsurgical TD-venous anastomosis assisted by TD catheterization for imaging guidance, resulting in decompression of the lymphatic system and resolution of the pulmonary symptoms.

Early Outcomes of Septal Myectomy for Obstructive Hypertrophic Cardiomyopathy in Children With Noonan Syndrome.

Noonan syndrome (NS) is a genetic syndrome causing obstructive hypertrophic cardiomyopathy (HCM) in infants. Studies of cardiac surgery in pediatric HCM patients with NS (NS-HCM) are lacking. We aim to characterize the early disease course of young NS-HCM patients before adolescence and assess their complications and survival condition after septal myectomy. Pediatric obstructive HCM patients who underwent septal myectomy at age 10 years or under were enrolled consecutively between 2009 and 2019. Ten patients with NS and 43 non-NS patients were enrolled in our study. NS-HCM patients were diagnosed at a younger age (5.00 ± 7.48 months vs. 18.73 ± 26.96 months) and more often had biventricular outflow tract obstruction (90.00% vs 30.23%). The surgical treatment can significantly reduce the pressure gradient of the outflow tract. More NS-HCM patients had biventricular reconstruction (70.00% vs 25.58%). The overall survival rates in all patients were 98.04% during 5-year follow-up, respectively. Complete heart block (CHB) was the most prevalent complication in patients with NS and tended to be more common than in non-NS patients (20% vs 7.32%). No sudden cardiac death (SCD) occurred in CHB patients who had pacemaker implantation. Biventricular reconstruction was the risk factor for CHB. Septal myectomy is safe and effective surgery to relieve obstruction in young age pediatric obstructive NS-HCM patients. Postoperative CHB is a common complication, especially in patients who underwent biventricular reconstruction. The implantation of pacemaker can protect CHB patients from SCD and improve their prognosis.

Blindness Secondary to Orbital Giant Cell Granuloma Mass-Effect in Noonan Syndrome With Return of Vision Following Surgical Decompression.

ABSTRACT: Noonan syndrome is a rare, autosomal dominant disorder encompassing multiple congenital defects, as well as association with solid tumor and lesion development. The authors present a 26-year-old female with known Noonan syndrome and ongoing complaint of worsening unilateral vision, progressing to vision loss due to lesion mass effect. Decompressive surgery was performed, restoring patient's vision to baseline immediately postoperative. The lesion was confirmed to be giant cell granuloma. In this paper we discuss the unique presentation of vision loss due to orbital giant cell granuloma in Noonan syndrome with postoperative return of vision; the importance of a multi-disciplinary team evaluation, thorough preoperative clinical and image-based work up, intraoperative findings, postoperative outcome, and complexity of definitive management.

Unroofing of Myocardial Bridging After Septal Myectomy in a Child With Noonan Syndrome.

Myocardial bridging is a controversial topic that remained with no well-defined management protocol. We present a ten-year-old child with Noonan syndrome and a myocardial bridge.

Multimodality lymphatic imaging of postoperative chylothorax in an infant with Noonan syndrome: a case report.

BACKGROUND: Chylothorax is a rare complication of pediatric cardiac operations that occurs more frequently in children with Noonan syndrome, a genetic disorder associated with cardiac defects and lymphatic anomalies. CASE PRESENTATION: We report a case of postoperative chylothorax in a 6-month-old infant with Noonan syndrome where multimodality lymphatic imaging guided management was followed. Drainage patterns of the lymphatic capillaries in the lower and upper extremities were visualized during near-infrared fluorescence lymphatic imaging (NIRFLI). Dynamic magnetic resonance lymphangiography (MRL) further identified the site of leakage in the thoracic duct and subsequently guided surgical intervention. CONCLUSIONS: Application of multimodality imaging allows for greater individualization of treatment and should be considered in patients with complex cases such as those with syndromes associated with a higher incidence of chylothorax. IRB Number: HSC-MS-13-0754, December 10, 2013.

Mitral valve replacement and trans-mitral myectomy for a child with Noonan syndrome accompanied by hypertrophic obstructive cardiomyopathy.

A 4-year-old boy with Noonan syndrome accompanied by hypertrophic obstructive cardiomyopathy presented with refractory heart failure owing to severe left ventricular outflow obstruction and mitral regurgitation. He underwent mitral valve replacement and trans-mitral myectomy. The pathology of the resected myocardium was consistent with hypertrophic cardiomyopathy, and the mitral valve leaflets were severely degenerated. Compared with a control patient who is a non-syndromic 4-year-old boy with hypertrophic obstructive cardiomyopathy, mitral pathology was much more severe in Noonan syndrome. Regarding trans-mitral myectomy, residual pressure gradient at the mid-ventricular level made us think about more aggressive muscle resection with various approaches.

Cardiac transplantation in children with Noonan syndrome.

NS and related RAS/MAPK pathway (RASopathy) disorders are the leading genetic cause of HCM presenting in infancy. HCM is a major cause of morbidity and mortality in children with Noonan spectrum disorders, especially in the first year of life. Previously, there have been only isolated reports of heart transplantation as a treatment for heart failure in NS. We report on 18 patients with NS disorders who underwent heart transplantation at seven US pediatric heart transplant centers. All patients carried a NS diagnosis: 15 were diagnosed with NS and three with NSML. Sixteen of eighteen patients had comprehensive molecular genetic testing for RAS pathway mutations, with 15 having confirmed pathogenic mutations in PTPN11, RAF1, and RIT1 genes. Medical aspects of transplantation are reported as well as NS-specific medical issues. Twelve of eighteen patients described in this series were surviving at the time of data collection. Three patients died following transplantation prior to discharge from the hospital, and another three died post-discharge. Heart transplantation in NS may be a more frequent occurrence than is evident from the literature or registry data. A mortality rate of 33% is consistent with previous reports of patients with HCM transplanted in infancy and early childhood. Specific considerations may be important in evaluation of this population for heart transplant, including a potentially increased risk for malignancies as well as lymphatic, bleeding, and coagulopathy complications.

Early Outcomes of Cardiac Surgery in Patients with Noonan Syndrome.

There is a paucity of cardiac surgery outcomes data for patients with Noonan syndrome (NS). Our objective was to evaluate early results in these patients. Between January 1999 and December 2015, 29 patients (18 males, 62%) with NS underwent cardiac surgery at our institution. Mean age was 23 ± 17.9 years; 12 (41%) were under 18 years of age. Fourteen patients (48%) had prior sternotomies. The primary operations for the main diagnosis were pulmonary valve/conduit replacement/repair (n = 14, 48%), septal myectomy for obstructive hypertrophic cardiomyopathy (n = 7, 24%), aortic valve replacement/repair (n = 4, 14%), atrial septal defect (ASD) repair (n = 2, 7%), and cardiac transplantation (n = 2, 7%). Concomitant procedures were performed in 24 patients (83%), most commonly right ventricular outflow tract reconstruction (n = 13, 45%), mitral valve repair/replacement (n = 7, 24%), and ASD repair (n = 6, 21%). Mean bypass and cross-clamp times were 88.8 ± 51 minutes and 54.7 ± 67 minutes, respectively. There was 1 early death (3%). Postoperative morbidity occurred in 18 patients (62%), most commonly arrhythmias (n = 14, 48%) or respiratory insufficiency/pneumonia (n = 6, 21%). There were 2 early reoperations and 4 early readmissions. Univariate factors associated with morbidity included male gender (P = 0.03) and longer cross-clamp time (P = 0.02). Median length of hospital stay was 6 days (interquartile range 5-10.5 days). Patients with NS frequently have multiple cardiac lesions requiring a broad spectrum of operations. Early mortality is low despite procedure complexity. Although early postoperative morbidity is common, patients overall do well with reasonable hospital lengths of stay. Additional studies are needed to evaluate long-term outcomes and quality of life.

Long-term results of the modified Konno procedure in high-risk children with obstructive hypertrophic cardiomyopathy.

OBJECTIVE: Transaortic septal myectomy is the gold standard surgery in obstructive hypertrophic cardiomyopathy, but it is not optimal for children aged less than 5 years and with right ventricular outflow tract obstruction. We evaluated outcomes with the modified Konno procedure in children with severe forms of obstructive hypertrophic cardiomyopathy. METHODS: A total of 79 consecutive children who underwent the modified Konno procedure in our center between 1991 and 2016 were included. RESULTS: Clinical features included age less than 5 years (38%), maximal septal thickness 25 mm or more (32%), extension to the left ventricular apex (29%), and right ventricular outflow tract obstruction (28%). In total, 25% of patients had Noonan syndrome. Five children (6%) aged less than 15 months with Noonan syndrome and biventricular obstruction died in the hospital. Mean follow-up was 6 ± 5.7 years. Survival without death and heart transplantation was 82% at 20 years. Atrioventricular block occurred in 9 patients (11%) and was associated with right ventricular outflow tract obstruction and surgery before 2010. Death, resuscitated sudden cardiac death, and appropriate implantable defibrillator shock were associated with maximal septal thickness before surgery (adjusted odds ratio, 1.20; 95% confidence interval, 1.07-1.35; P = .002) and need for an associated procedure (adjusted odds ratio, 8.84; 95% confidence interval, 2.01-38.93; P = .004). There was no case of recurrent obstruction. Reoperation was required in 4 patients (5%) for other reasons. CONCLUSIONS: The modified Konno procedure provided durable obstruction relief and good long-term survival in children with severe forms of obstructive hypertrophic cardiomyopathy. Children with Noonan syndrome undergoing surgery early in life were at higher risk of early mortality.

Giant cell lesion of the jaw as a presenting feature of Noonan syndrome.

This is a case of a 20-year-old woman who presented with a left jaw mass which was resected and found to be a giant cell granuloma of the mandible. Her history and physical examination were suggestive for Noonan syndrome which was confirmed with genetic testing and the finding of a PTPN11 gene mutation which has rarely been associated with giant cell lesions of the jaw. Given her particular genetic mutation and the presence of a giant cell lesion, we present a case of Noonan-like/multiple giant cell lesion syndrome.

Results of balloon pulmonary valvoplasty in children with Noonan's syndrome.

Pulmonary valve stenosis is common in patients with Noonan's syndrome. The response to balloon valvoplasty varies.We assessed the correlation between re-intervention rate, immediate response, and the progress of the valve gradient over time after intervention. METHODS: This is a retrospective study conducted from 1995 to 2014. RESULTS: Of 14 patients identified, seven had re-intervention 28±54 months (range 3-149, median 3.3) after valvoplasty. These patients did not have a significant decrease in gradient after intervention. Their gradient subsequently decreased during follow-up and then became static before increasing years after intervention. In contrast, the gradient of patients not requiring further intervention continually reduced over time. Demographics did not differ between these groups. CONCLUSION: We could not identify predisposing factors for long-term success of pulmonary valvoplasty in Noonan's patients, but the trajectory of gradients differs significantly between patients needing re-intervention from those who remain free from re-intervention.