The Cleft Palate–Craniofacial Journal 52(2) pp. 183–191 March 2015 Ó Copyright 2015 American Cleft Palate–Craniofacial Association

ORIGINAL ARTICLE Perioperative Risk Factors in Patients With 22q11.2 Deletion Syndrome Requiring Surgery for Velopharyngeal Dysfunction Carrie Stransky, M.D., Marten Basta, B.S., Donna M. McDonald-McGinn, M.S., Cynthia B. Solot, M.A., C.C.C., Denis Drummond, M.D., Elaine Zackai, M.D., Don LaRossa, M.D., Richard Kirschner, M.D., Oksana Jackson, M.D. Objective: To determine the prevalence of cardiac, cervical spine, and carotid artery abnormalities in patients with 22q11.2 deletion syndrome (22q11.2DS) undergoing surgery for velopharyngeal dysfunction (VPD), associations between the presence of these abnormalities, and whether these abnormalities caused changes in surgical management or perioperative complications. Design: Retrospective review. Setting: Tertiary pediatric hospital. Patients: Seventy patients with 22q11.2DS with complete preoperative cervical vascular and spine imaging and cardiac evaluation between 1998 and 2011. Main Outcome Measures: Incidence of cardiac, cervical spine, and vascular abnormalities; related perioperative complications; and resulting changes in surgical, anesthetic, or perioperative management plan. Results: Cardiac abnormalities occurred in 45 patients (64.3%), and 8 patients required cardiac anesthesia. Thirty-eight patients (54.3%) had at least one vascular abnormality of the neck, and 14% had medial deviation of the internal carotid artery. Surgery was not performed in one patient, and the surgical plan was altered in three patients because of carotid anomalies. Cervical spine abnormalities were found in 24 patients (34.3%); 8 patients demonstrated radiographic evidence of cervical instability and were treated with spinal precautions during surgery. The presence of one anomaly was not predictive of any other finding, and there were no complications related to the heart, cervical spine, or carotid arteries. Conclusions: Anomalies of the heart, cervical spine, and cervical vasculature occur frequently in 22q11.2DS, vary drastically in severity, and are impossible to predict based on other features of the syndrome. Preoperative diagnosis of these comorbidities with routine imaging can minimize the risk of avoidable surgical complications. KEY WORDS:

22q11.2 deletion, carotid, c-spine, velopharyngeal insufficiency

Dr. Stransky is General Surgical Resident, Jefferson Medical College, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania. Mr. Basta is medical student, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania. Ms. McDonald-McGinn is Clinical Professor of Pediatrics, Associate Director, Clinical Genetics Center and Program Director, 22q and You Center, The Children’s Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania. Ms. Solot is Senior Speech-Language Pathologist, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania. Dr. Drummond is Professor of Surgery, Division of Orthopedic Surgery, The Children’s Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania. Dr. Zackai is Professor of Pediatrics, Director, Clinical Genetics Center, and Medical Director, The Children’s Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania. Dr. LaRossa is Emeritus Professor of Surgery, Division of Plastic Surgery, The Children’s Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania. Dr. Kirschner is Professor of Clinical Surgery and Pediatrics, The Ohio State University College of Medicine, and Chief, Section of Plastic and Reconstructive Surgery, Nationwide Children’s Hospital, Columbus, Ohio. Dr. Jackson is Assistant Professor of Surgery, Division of Plastic Surgery, The Children’s Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.

The 22q11.2 deletion syndrome (22q11.2DS) is the most common microdeletion syndrome and one of the most frequent with both palatal and cardiovascular involvement. Although suspected to be underrecognized because of its clinical variability, 22q11.2DS has an estimated prevalence of 1:2000 to 1:4000 live births in the Unites States (Scambler et al., 1992; Shprintzen et al., 2005). The classic clinical findings include immunodeficiency (77%), palatal involve-

Presented at the 8th Biennial International 22q11.2 Deletion Syndrome Meeting, Orlando, Florida, July 8, 2012; Annual Meeting of the American Society of Plastic Surgery, New Orleans, Louisiana, October 28, 2012; and 12th International Congress on Cleft Lip/Palate and Related Craniofacial Anomalies, Orlando, Florida, May 6, 2013. Submitted August 2013; Revised December 2013; Accepted January 2014. Address correspondence to: Dr. Oksana Jackson, Division of Plastic Surgery, The Children’s Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, 3501 Civic Center Boulevard, 9th Floor Colket Building, Philadelphia, PA 19104. E-mail [email protected]. DOI: 10.1597/13-206 183

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ment (76%), and congenital heart disease (75%). Other findings include endocrine dysfunction (50%), gastrointestinal disorders (35%), renal disease (35%), and variable developmental delay/intellectual deficits, with 25% developing schizophrenia in adulthood (Bassett et al., 2002; Bassett et al., 2011). Based on previous reports in the literature, anomalies of the cervical spine and neck vasculature also are frequently identified during evaluation (MacKenzie-Stepner et al., 1987; Ricchetti et al., 2004; Oppenheimer et al., 2010). Palatal involvement occurs in up to 75% of patients and includes palatal clefting and velopharyngeal dysfunction (VPD) in the absence of overt or submucosal clefts. Congenital VPD in this population can result from dysfunction of the velopharyngeal musculature and from velopharyngeal disproportion characterized by a deep pharynx and relatively short palate (Dyce et al., 2002). Affected children also can have significant speech and language delays and often present with both hypernasal resonance and compensatory articulation errors due to velopharyngeal insufficiency. Patients with 22q11.2DS and palatal involvement with significant speech disorders typically present seeking surgical intervention in early childhood (Shprintzen, 2008). Surgical decision making in this population is complex, and preoperative workup is paramount to optimizing speech outcomes and minimizing perioperative complications. The potential comorbidities of cardiac, vascular, and cervical spine anomalies in 22q11.2DS are particularly relevant to these patients undergoing pharyngeal surgery for VPD (McDonald-McGinn et al., 1997). Numerous abnormalities of the great vessels and cervical vasculature have been reported, including medialization of the internal carotid arteries, potentially placing them into the surgical field and therefore at risk for injury during pharyngoplasty (MacKenzie-Stepner et al., 1987; Oppenheimer et al., 2010). Cervical spine anomalies such as bony nonunion and multilevel fusion with the potential for cervical instability also have been reported with a high frequency. Instability of the cervical spine, particularly during extension of the head and neck, can lead to compression of the subarachnoid space and injury to the spinal cord. We previously reported at least one cervical spine anomaly in 100% of patients studied with 22q11.2DS, with platybasia in 91%, dysmorphia of the atlas in 75%, fusion of at least one level in 28%, and increased segmental motion in 56% (Ricchetti et al., 2004). Consequently, before proceeding with pharyngeal surgery for VPD, our institution requires thorough preoperative evaluation of the heart, carotid arteries, and the cervical spine. The purpose of this study was to present our experience with these comorbidities in patients with 22q11.2DS undergoing pharyngeal surgery to treat VPD at our institution. We sought to better understand the prevalence of cardiac, cervical vascular, and cervical spine pathology in this population; to assess for any associations between these

anatomic abnormalities; and to determine if abnormalities in these systems resulted in any changes in surgical management or in perioperative complications. Our goal was to determine if evidence exists to support our preoperative protocol for evaluating these congenital anomalies in patients with 22q11.2DS, as well as to provide additional information that may assist surgeons in their decision making about preoperative testing as well as counseling of families with this condition about operative risks. METHODS After Institutional Review Board approval was obtained at our institution, a retrospective chart review was performed of all patients with 22q11.2DS who were candidates for pharyngeal surgery for VPD from 1998 to 2011. The diagnosis of 22q11.2DS was confirmed in all patients by fluorescence in situ hybridization (FISH) analysis, multiplex ligation-dependent probe amplification, or array technologies, and all patients were evaluated by the interdisciplinary ‘‘22q and You’’ Center at the Children’s Hospital of Philadelphia. Once referred to the Division of Plastic Surgery, each patient was evaluated by one of two speech pathologists to assess velopharyngeal function using the Pittsburgh Weighted Speech Scale for Velopharyngeal Competence. Patients with significant VPD were further evaluated with nasoendoscopy or videofluoroscopy to visualize the degree and pattern of velopharyngeal closure. Age, language status, articulation, extent of speech therapy, and medical comorbidities were also considered in the decision to recommend the timing of pharyngeal surgery. Only patients for whom surgery was recommended were considered in this review. Surgical candidates underwent preoperative evaluation including magnetic resonance angiography (MRA) or computed tomography angiography (CTA) of the neck to evaluate the cervical vasculature, cervical spine x-rays (sixview radiographs including AP, lateral, flexion, extension, open mouth, and skull base) with or without computed tomography (CT), or magnetic resonance imaging (MRI) of the cervical spine, as well as a thorough cardiac evaluation including echocardiogram or CT of the thorax if not previously performed. For many patients with known congenital heart disease, a letter of clearance from their pediatric cardiologist was obtained before proceeding with surgery, and no new testing was required. Results from each preoperative study were recorded, and the presence and type of abnormalities were noted. Results were analyzed to determine if any significant relationships existed between cervical vascular, cervical spine, and cardiac findings. The perioperative record was also queried to determine if any changes were made in the surgical plan, anesthetic plan, or perioperative management plan based on these preoperatively identified abnormalities, as well to determine the incidence of related perioperative complica-

Stransky et al., PERIOPERATIVE RISK FACTORS FOR PHARYNGEAL SURGERY IN 22Q11.2 SYNDROME

TABLE 1

Cardiac Abnormalities

TABLE 2

Abnormality

Number

Rate (%)

Total Tetralogy of Fallot Ventricular septal defect Atrial septal defect Right aortic arch Vascular ring Patent ductus arteriosus Other*

45 13 14 6 7 4 3 6

64.3 18.6 20.0 8.6 10.0 5.7 4.3 8.6

* Includes bicuspid aortic valve (n ¼ 2), truncus arteriosus (n ¼ 2), tortuous aortic arch (n ¼ 1), and situs solitus (n ¼ 1).

tions. Statistical analysis was achieved using STATA. Chisquare and Fisher exact tests were used for categorical variables when appropriate, and the Mann-Whitney test for continuous variables was employed. RESULTS Eighty patients with 22q11.2DS were identified who were candidates for VPD surgery from 1998 to 2011. Seventy patients had complete imaging available for review and were included in the study. Thirty-four (49%) patients were female, and 36 (51%) were male. The average age at surgery was 6.9 years (range, 3 to 16 years). Sixty-three (90%) patients underwent posterior pharyngeal flap, 6 (8.6%) underwent sphincter pharyngoplasty, and 1 patient was a surgical candidate but because of significant neck vessel abnormalities noted on preoperative imaging, the surgery was not performed. Heart and Great Vessels Abnormalities of the heart and great vessels were present in 45 (64.3%) patients, the most common of which included ventricular septal defect (14), Tetralogy of Fallot (TOF; 13), and right aortic arch (7; Table 1). Of these 45 patients, 36 had at least one open cardiac surgery in infancy or childhood prior to presenting for VPD surgery, and 10 had multiple cardiac surgeries (average ¼ 2.9 procedures). All patients with congenital cardiac disease received preoperative clearance from cardiology with review of their cardiac records by the cardiac anesthesia screening center at our institution. Five patients had hemodynamically significant lesions at the time of their surgery for VPD and were managed chronically with multiple cardiovascular medications, and a total of nine patients required cardiac anesthesia based on the recommendation of their cardiologist or cardiac anesthesia. The diagnosis in these nine patients included TOF (6), interrupted aortic arch type B (1), aortic valve dysfunction with heart block and a pacemaker (1), and truncus arteriosus with high-grade AV block and a dual-chamber pacemaker (1). This last patient was anticoagulated with Coumadin for a

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Vascular Abnormalities of the Neck Abnormality

Number

Rate (%)

Total

38

54.3

Carotid artery Low bifurcation Medialization Aberrant location of subclavian or vertebral artery Replaced origin of vessel Nonvisualization Other*

22 10 10 14 8 5 7

31.4 14.3 14.3 20 11.4 7.1 10

* Includes innominate artery bifurcation in neck (n ¼ 1), prominent anterior superficial neck veins (n ¼ 1), hypoplastic vertebral artery (n ¼ 1), tortuous internal carotid artery (n ¼ 2), common trunk of bilateral common carotid arteries (n ¼ 1), and common carotid artery in anterior location (n ¼ 1).

mechanical St. Jude’s heart valve and required an extended hospitalization and a tailored cardiac management plan for perioperative heparinization. No cases were cancelled for cardiac reasons, although the patient with truncus arteriosus described above had his surgery postponed because of recurrent and progressive truncal valve insufficiency and stenosis after valvuloplasty 9 months earlier, which required repeat cardiac surgery for placement of the St. Jude’s valve. No cardiac events occurred intraoperatively or postoperatively in any patient in this study. Vascular Abnormalities of the Neck Vascular abnormalities of the neck were noted in 38 (54.3%) patients, with 22 (31.4%) having documented carotid artery abnormalities (Table 2). The most common abnormalities included a low bifurcation of the common carotid artery (10) and medial deviation of the internal carotid artery (10; Fig. 1). Vertebral and subclavian artery anomalies were also noted, including an abnormal course, origin, or size of the vessel, often in combination (14). An aberrant course of the subclavian artery was noted within the neck in 12 patients, which was commonly in a retroesophageal position, and the vertebral was diminutive in size or had an altered course in two patients. Eight patients had an abnormal arch origin of the neck vessels, and 87.5% of these patients had a concurrent cardiac abnormality. No cases were cancelled intraoperatively because of concern for carotid artery injury at our institution, although one patient had a history of an aborted pharyngoplasty elsewhere due to very prominent pulsations noted during surgery. This patient subsequently underwent imaging, which revealed a medially deviated left internal carotid artery. Posterior pharyngeal flap surgery was planned at our institution; intraoperatively, with neck extension, pulsations were noted but limited to the lateral pharyngeal recess, and pharyngoplasty proceeded uneventfully with no alteration of the original surgical plan.

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FIGURE 1 Cervical MRI of a patient with 22q11.2DS demonstrating marked medial deviation of the internal carotid arteries right greater than left, with the right carotid artery visibly bulging into the oropharyngeal airway (white arrow).

Surgery was not performed in one patient because of severe abnormalities of the cervical and cerebral vascular arterial systems. During routine preoperative workup, this patient was found to have a dominant left internal carotid artery in a submucosal position with significant medial deviation into the retropharyngeal space approaching midline, as well as a diminutive right internal carotid artery. In addition, the left vertebral artery was not visualized and the right was enlarged and tortuous. The cerebral vascular system was characterized by an incomplete Circle of Willis, with the medially displaced left internal carotid artery solely supplying the left middle cerebral circulation, as well as both anterior cerebral artery circulations (Fig. 2). These findings were initially described on standard MRA imaging of the neck and brain and repeated with hyperextension of the neck with no resultant change seen in the left internal carotid artery position. The surgical plan was modified in three patients because of their carotid artery anomalies. In one patient, this change occurred intraoperatively, and in two others, an altered plan was anticipated preoperatively. In one patient, sphincterpharygoplasty was planned based on the velopharyngeal closure pattern, and preoperative imaging revealed medial deviation of both internal carotid arteries, more severe on the right. Intraoperatively, prominent pulsations were localized to the area behind the right tonsillar pillar and in the right lateral pharynx, which did not vary with neck extension. Therefore, the plan was changed to a posterior pharyngeal flap, and the

FIGURE 2 MR angiogram of a patient with 22q11.2DS demonstrating a dominant left carotid artery with medial deviation of the internal branch, a diminutive right internal carotid, enlarged right vertebral artery, and nonvisualized left vertebral artery. The patient was considered too high risk for surgery because of the finding that both anterior cerebral circulations and the left middle cerebral relied on the medialized left internal carotid, with no collateralization within the Circle of Willis.

right internal carotid artery was successfully retracted laterally through the mucosa with a blunt malleable to allow for the creation of a moderately wide flap. In another patient, the preoperative plan was changed from a sphincterpharyngoplasty to a posterior pharyngeal flap after imaging revealed a significantly deviated left internal carotid. In this case, prominent pulsations were again noted intraoperatively, localized to the left lateral pharyngeal wall behind the tonsillar pillar, and the pillar and artery were successfully retracted laterally, allowing for uncomplicated creation of a wide posterior pharyngeal flap. In the third patient, a posterior pharyngeal flap was planned, but because of bilateral internal carotid artery deviation, restriction of the flap width was anticipated. A conservative approach with a narrower flap if necessary was discussed with the family preoperatively given this patient’s comorbid severe cardiac disease and chronic anticoagulation. Computed tomography angiography in this patient revealed a submucosal left internal carotid artery with mild medial deviation described as abutting the lateral wall of the oropharyngeal airway, as well as a severely deviated right internal carotid artery. The right internal carotid was described as occupying a retropharyngeal position approximately 1.5 to 2.0 cm below the level of the hard palate, and at the level of the hard palate, a distance of 2.0 cm was measured between the internal carotid arteries. Intraop-

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TABLE 3

Cervical Spine Abnormalities

Abnormality

Number

Rate (%)

Total Fusion of one or more levels Nonunion of spinal elements Hypoplasia of spinal elements Other*

24 9 5 5 7

34.3 12.9 7.1 7.1 10.0

TABLE 4 Radiographic Findings and Orthopedic Recommendations for Eight Patients With Cervical Spine Instability

Patient

Imaging Modality

1

MRI

2

X-ray

3

CT

4

MRI

5

CT

6

X-ray

7

CT

8

X-ray

* Includes short and posterior odontoid (n ¼ 2), cervical ribs at C7 (n ¼ 1), loss of normal lordosis (n ¼ 1), subluxation (n ¼ 2), and flattening of discs C3-C6 (n ¼ 1).

erative inspection revealed prominent right lateral pharyngeal pulsations and no change with neck extension; the flap was limited to a moderate width and was successfully raised with blunt lateral retraction of the internal carotid artery. Thus, in a total of four patients at our institution, the surgical plan was affected by the presence of significant internal carotid artery abnormalities (cancelled in one patient and altered in three others). No intraoperative or postoperative complications occurred related to carotid artery malposition. Cervical Spine Twenty-four (34.3%) patients had anomalies of the cervical spine (Table 3). The most common findings were fusion of one or more cervical spine levels (9), a hypoplastic C1 (5), and nonunion of spinal elements (5; Fig. 3). When evaluating patients for stability, eight (33.3%) of those with cervical spine anomalies demonstrated evidence of instability radiographically and were

FIGURE 3 CT scan of the cervical spine demonstrating nonunion of the anterior and posterior arches of C1 with a gap of 4 mm and 15 mm in a patient with 22q11DS.

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Findings Fusion C2–C3, hypoplastic odontoid, high anterior arch of C1, no evidence of cord compression in neutral/flexion/ extension positions Fusion C1–C2, hypoplastic odontoid, partial occipitalization of C1 Unfused anterior and posterior arches of C1 C1–C2 subluxation with 7-mm difference between flexion/ extension, basilar invagination, clivus foreshortening, partial fusion C1-occiput, dysplastic dens Hypoplastic odontoid, anterior atlas defect, subaxial fusion C2–C3 posterior elements, C1 mild left lateral subluxation, lack of fusion anterior and posterior elements C1 Nonosseous fusion posterior elements C2– C3, mild atlantooccipital instability with 3-mm subluxation with extension Incomplete C1 ring with nonfusion of anterior and posterior arches and hypoplastic C1 lateral masses Hypoplastic C1, abnormal dens shape, mild instability C1–C3 and atlanto-occipital instability, 3-mm subluxation of both with flexion/extension

Orthopedic Recommendations Neutral head positioning, spinal monitoring

Neutral head positioning, no hyperextension Avoid prolonged neck extension Neutral head positioning

Avoid prolonged neck extension

Neutral head positioning

Neutral head positioning, spinal monitoring

Neutral head positioning

therefore managed with spinal precautions during surgery. Two patients required spinal monitoring throughout the procedure, and the remainder were treated with no or very minimal neck extension based on the recommendations made by the preoperative orthopedic consultants. All of these eight patients had complex cervical spine abnormalities involving hypoplasia and nonunion of spinal elements, often in combination with abnormal fusions at different levels, as described in more detail in Table 4. The two patients who required spinal monitoring had incomplete C1 rings, the first with nonfusion of the anterior and posterior arches and hypoplastic lateral masses and the

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TABLE 5 Association Between Neck Vasculature, Cardiac, and Cervical Spine Abnormalities Abnormality

Number

Rate (%)

P Value

Carotid artery With other neck vascular With cardiac With cervical spine

22 11 15 9

31.4 50 68.2 40.9

— .386 .831 .585

All neck vascular With cardiac With cervical spine

38 27 16

54.3 71.1 42.1

— .546 .29

Cardiac With carotid artery With all neck vascular With cervical spine

45 15 20 15

64.3 33.3 44.4 33.3

— .738 .982 .875

Cervical spine With other neck Vascular With cardiac With cervical spine

24 9

34.3 37.5

— .572

12 15

35.3 62.5

.919 .916

second with no ossification of the anterior arch, fusion of C2–C3 with a very narrow disc space, and a hypoplastic odontoid. No adverse outcomes were noted perioperatively related to these cervical spine anomalies. Statistical Analysis Overall, the presence of one type of anomaly did not determine a statistically significant propensity for any other abnormality, and no statistical difference was noted between genders for any of the three organ systems studied (Tables 5 and 6). However, 71% of patients with an abnormality of the neck vasculature had a concordant cardiac anomaly, and 62.5% of patients with abnormalities of the spine also had a cardiac abnormality. DISCUSSION The 22q11.2DS is a complex multisystem disorder that can present with variable expression of its many clinical features. Pharyngeal surgery to correct VPD in this disorder can result in substantial improvements in speech intelligibility and communication, affect social functioning, and result in a significant improvement in quality of life for children affected with 22q11.2DS and their families. Although pharyngeal surgery for VPD is relatively short and low risk, the complex nature of these patients has led to various screening recommendations to minimize perioperative complications at our institution and others (Hultman et al., 2000; Tatum et al., 2002). The decision to proceed with preoperative testing should be carefully considered based on clinical evidence and the risk-to-benefit ratio. Extensive testing can increase health care costs and incur substantial expenses on families. In addition, radiology studies that may require radiation or sedation are not without risk and inconvenience.

TABLE 6 Gender Distribution of Neck Vasculature, Cardiac, and Cervical Spine Anomalies Sex, N (%) Abnormality

n

Total Carotid artery All neck vasculature Cardiac Cervical spine

70 22 38 45 24

Male 36 13 19 27 11

(51.4) (59.1) (50.0) (60.0) (45.8)

Female 34 9 19 18 13

(48.6) (40.9) (50.0) (40.0) (54.2)

P Value — .543 1 .094 .671

Most congenital anomalies of the heart and great vessels are identified prenatally or soon after delivery. However, some lesions, such as vascular rings, which may not cause hemodynamic instability at birth, can present later with progressive respiratory or gastrointestinal symptoms. (Bonnard et al., 2003; Shah et al., 2007). Because of the high prevalence of documented cardiac anomalies among patients with 22q11.2 DS, a standard chest x-ray, electrocardiogram, and echocardiogram have been recommended for all new patients, even in the absence of clinical signs and symptoms of cardiac disease (Geis et al., 1981; Shprintzen et al., 1985; Goldmuntz et al., 1998). Those with significant structural disease typically undergo correction in infancy, and some patients with severe disease can require multiple operations in childhood and adolescence. In line with the overall incidence of cardiac disease in 22q11.2DS, 64% of our patients had documented congenital abnormalities of their heart and great vessels, and 51% had previously undergone open cardiac surgery. More relevant to assessing perioperative risk at the time of VPD surgery, five patients were managed chronically with multiple cardiovascular medications for hemodynamically significant lesions, two of these patients had pacemakers in place for heart block, one patient was anticoagulated for a mechanical valve, and a total of nine patients required cardiac anesthesia based on the recommendation of their cardiologists or the cardiac anesthesia team. We did not have any perioperative cardiac complications; however, the high overall incidence of cardiac disease in patients with 22q11.2 DS, and the ongoing severity in a smaller subset, makes careful preoperative assessment and attention to cardiac precautions when necessary prudent. Previous studies have described alterations in the neck vasculature in the 22q11.2DS population, particularly medialization of the internal carotid arteries, placing them at potential risk for injury during pharyngeal surgery (D’Antonio and Marsh, 1987; Hultman et al., 2000; Tatum et al., 2002; Chegar et al., 2006; Oppenheimer et al., 2010; Swanson et al., 2011). Conflicting opinions exist as to the true risk of injury to the carotids when medialization is present, because of the ability to visualize or palpate pulsations intraoperatively, the use of careful operative technique, and the tendency for lateralization of the carotids to occur with the neck positioned in extension for surgery (Witt et al., 1998; Mehendale and Sommerlad,

Stransky et al., PERIOPERATIVE RISK FACTORS FOR PHARYNGEAL SURGERY IN 22Q11.2 SYNDROME

2004). Several reports, however, have described a lack of correlation between observed pulsations and the medially or submucosally displaced internal carotid artery, and many surgeons continue to be convinced of the utility of preoperative imaging (D’Antonio and Marsh, 1987; MacKenzie-Stepner et al., 1987; Mitnick et al., 1996; Witt et al., 1998; Hultman et al., 2000; Tatum et al., 2002; Lai et al., 2004; Oppenheimer et al., 2010). No written reports exist documenting carotid artery injury during pharyngoplasty, although exposure of the internal carotid artery during flap dissection has been reported (Shprintzen, 1998; Mehendale et al., 2004). Excess intraoperative bleeding requiring a 2-unit blood transfusion in a patient with 22q11.2DS and a medially displaced internal carotid artery, documented by preoperative MRA, was described recently by Swanson et al. (2011). The internal carotid itself was not injured; the source of bleeding was unclear but speculated to result from cutting the ascending pharyngeal artery of one of its branches (Swanson et al., 2011). Other reports exist, as in a patient described in this series, in which pharyngoplasty was abandoned intraoperatively because of concerning pulsations, incurring unnecessary risk, medical costs, and delaying necessary surgery (Shprintzen, 1998). A few, very severe, congenital carotid anomalies have been reported, reemphasizing how preoperative knowledge can affect surgical decision making. Johnson et al. (2010) described a patient with 22q11.2DS with congenital absence of one internal carotid artery with its subsequent vascular territory obtaining collateral flow from branches of the external carotid artery. At our institution, the patient described in Figure 2 had a medialized and submucosal left internal carotid artery, which solely supplied both anterior cerebral and the left middle cerebral circulations; carotid artery injury in this patient could theoretically result in catastrophic cerebrovascular ischemia. In our series, no intraoperative or postoperative complications were identified related to carotid artery malposition; however, the surgical plan was altered because of significant internal carotid artery abnormalities in a total of four patients. Numerous and frequent congenital anomalies of the upper cervical spine and craniovertebral junction have been described in the 22q11.2 DS population (Selnes, 1997; Siegel-Bartelt, 1997; Hultman et al., 2000; Ricchetti et al., 2004; Ricchetti et al., 2008). In 2000, in a prospective study assessing 41 children presenting to their craniofacial center with the diagnosis of 22q11.2DS, Hultman et al. reported the association of Chiari type 1 malformations and cranial nerve defects in 22q11.2DS and described numerous other anomalies including occipitalization of the atlas, narrowing of the foramen magnum, subluxation, and odontoid invagination. A total of 42% of patients had abnormalities of the craniovertebral junction, 34% of patients had demonstrated neurologic deficits, and one patient required suboccipital craniectomy with laminectomy for decompression (Hultman et al., 2000).

189

Studies at our institution have further elucidated the cervical and occipital pathology in this population. In 79 consecutive patients with 22q11.2DS evaluated clinically and radiographically, at least one developmental variation in the cervical spine or occiput was observed in every patient. Increased segmental motion was observed in 56% of patients, with one third showing increased mobility at more than one level. However, only three patients in this series, who were all older than 15 years, had neurologic symptoms potentially associated with cervical myelopathy secondary to cervical spinal stenosis, such as coordination and fine motor difficulties, radicular pain, and weakness, thus raising the question of whether the increased mobility observed represents true spinal instability, with its potential risk of myelopathy or an increased ligamentous laxity, with little or no clinical consequence (Ricchetti et al., 2004). In a follow-up study using advanced imaging (CT/MRI) in 32 patients with 22q11.2DS who had either neurologic symptoms or radiographic evidence of cervical spine instability (increased segmental motion on flexion/extension views), 40 pathologies not evident on plain radiographs with potential mechanical and/or neurologic implications were identified, including two cases of spinal canal encroachment (space available for the cord ,13 mm) and 3 three cases of spinal cord impingement. Compared with age-matched controls, the patients in this study were found to have significantly smaller spinal canal and spinal cord dimensions, four patients had documented neurologic symptoms, and one required surgical intervention (Ricchetti et al., 2008). We could not find any reported cases of spinal cord injury during velopharyngeal surgery in the 22q population. Although in our series, eight patients demonstrated evidence of instability radiographically and were therefore managed with spinal precautions during surgery, we also have not experienced any neurologic problems during velopharyngeal surgery. We have, however, observed one child with an extension positioning of the head and neck during a dynamic MRI study who developed a rapid drop in blood pressure and tachycardia. Timely response to this by providing a normal positioning of the head and neck rapidly normalized the blood pressure and heart rate. This case appears to highlight the potential risk associated with prolonged extension of the head and neck in these children. Thus, we continue to recommend careful evaluation of the cervical spine prior to surgical procedures and particularly when the positioning of the head and neck in a prolonged extension is required for the duration of the surgery, as prolonged extension can cause risk for spinal cord injury in the setting of cervical instability. CONCLUSION The results of our retrospective review again confirm that anomalies of the heart, cervical spine, and cervical vasculature do occur in significant numbers in this

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population and are impossible to predict based on other features of the syndrome. Our analysis between these anomalies revealed no statistical correlations—confirming the expression of clinical features follows no discernable pattern, the hallmark of this disorder. Children who may seem mildly affected without congenital heart disease or severe dysmorphic features are equally likely to have significant carotid deviation or anomalies of the cervical spine, which are impossible to predict without adequate imaging. This review demonstrates that these anomalies can range from mild anatomic abnormalities without clinical significance to severe disease in a small minority and can potentially place these patients at increased risk for complications, even during minor surgery. It is debatable whether the information presented here justifies the recommendation to perform costly routine imaging of the cervical spine and cervical vasculature prior to pharyngeal surgery given the rarity of severe disease, as well as the absence of complications in our series or reported in the literature. We cannot conclude that our practices have resulted in any difference in perioperative complications; however, as all patients treated at our center were subject to the same thorough preoperative imaging protocol, it is conceivable that our practices directly enabled these safe outcomes. We did alter our management of four patients with carotid anomalies and eight patients with cervical spine anomalies after discovery of the severity of their anomalies, but overall, this represents a small percentage of our cohort. Without a comparison group treated without imaging, we cannot conclude our protocol results in safer outcomes or advocate its use as evidence based. The information presented here does highlight the importance of thoughtful surgical decision making in this population in light of their multiple, often complex, congenital anomalies and does provide additional information to counsel patients and their families preoperatively about potential risks or outcomes, whether or not the surgeon has chosen to perform these studies. At our institution, to provide families with full informed consent and to achieve the safest outcomes, we continue to perform routine preoperative cardiac screening, as well as imaging of the cervical spine and cervical vasculature in all patients with 22q11.2DS prior to surgery in the pharyngeal region according to the following protocol: 1. All new patients with 22q11.2DS routinely receive a six-view radiographic evaluation that includes AP, lateral, flexion, extension, open mouth, and skull base of the cervical spine. These are best obtained approaching the fourth birthday when the bones are better ossified and the child can likely cooperate without the head having to be forced into position for the film. 2. Computed tomography scans are seldom used in order to avoid radiation exposure. Despite this,

3.

4.

5.

6.

occasionally multiple anomalous vertebrae can hinder an accurate radiograph evaluation, particularly in the immature spine of young children. In this situation, CT scans may be helpful. Magnetic resonance imaging is the best method to evaluate spinal stenosis or narrowing of the spinal canal, segmental spinal instability, and the intrusion of boney vertebral elements into the subarachnoid space. A dynamic MRI is recommended when significant instability is observed in the radiograph flexion and extension views. Evaluation of the neck using MR or CT is used to evaluate vascular anatomy and exclude carotid artery deviation. An MR study is preferred to avoid radiation exposure, but a CTA may be indicated when metallic cardiac valves or other metallic implants are present. Echo or CT of the thorax aids in evaluating the heart and great vessels, or preoperative cardiac clearance is needed from the patient’s cardiologist if known congenital heart disease exists.

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