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Figure 1.
Degrees of hypernasality in the control group (A) and the velocardiofacial syndrome group (B) after pharyngoplasty. Dark blue indicates always; light blue, sometimes; and light grey, never. X indicates insufficient data.

Degrees of hypernasality in the control group (A) and the velocardiofacial syndrome group (B) after pharyngoplasty. Dark blue indicates always; light blue, sometimes; and light grey, never. X indicates insufficient data.

Figure 2.
Closure patterns in the control group (A) and the velocardiofacial syndrome group (B) after pharyngoplasty. Dark blue indicates never; dark grey, sometimes; light blue, often; and light grey, always. X indicates insufficient data.

Closure patterns in the control group (A) and the velocardiofacial syndrome group (B) after pharyngoplasty. Dark blue indicates never; dark grey, sometimes; light blue, often; and light grey, always. X indicates insufficient data.

Table. 
Nasometric Results in the Velocardiofacial Syndrome and Control Groups
Nasometric Results in the Velocardiofacial Syndrome and Control Groups
1.
Willging  JPCotton  RT Velopharyngeal insufficiency. Bluestone  CDPediatric Otolaryngology. Vol 2. Philadelphia, PA Saunders2002;1789- 1800
2.
Haapanen  ML Nasalance scores in patients with a modified Honig velopharyngeal flap before and after operation. Scand J Plast Reconstr Surg Hand Surg 1992;26 (3) 301- 305
PubMed
3.
Mink van der Molen  ABJanssen  KSpecken  TFStubenitsky  BM The modified Honig velopharyngoplasty: a new technique to treat hypernasality by palatal lengthening [published online February 1, 2008]. J Plast Reconstr Aesthet Surg
PubMed10.1016/jobjps.2007.12.023
4.
Devriendt  KFryns  JPMortier  Gvan Thienen  MNKeymolen  K The annual incidence of DiGeorge/velocardiofacial syndrome. J Med Genet 1998;35 (9) 789- 790
PubMed
5.
Shprintzen  RJGoldenberg  RBLewin  ML  et al.  A new syndrome involving cleft palate, cardiac anomalies, typical facies, and learning disabilities: velo-cardio-facial syndrome. Cleft Palate J 1978;15 (1) 56- 62
PubMed
6.
Meinecke  PBeemer  FASchinzel  AKushnick  T The velo-cardio-facial (Shprintzen) syndrome. Eur J Pediatr 1986;145 (6) 539- 544
PubMed
7.
Lipson  AHYuille  DAngel  MThompson  PGVandervoord  JGBeckenham  EJ Velocardiofacial syndrome: an important syndrome for the dysmorphologist to recognize. J Med Genet 1991;28 (9) 596- 604
PubMed
8.
Goldberg  RMotzkin  BMarion  RScambler  PJShprintzen  RJ Velo-cadio-facial syndrome: a review of 120 patients. Am J Med Genet 1993;45 (3) 313- 319
PubMed
9.
Zim  SSchelper  RKellman  RTatum  SPloutz-Snyder  RShprintzen  R Thickness and histological and histochemical properties of the superior pharyngeal constrictor muscle in velocardiofacial syndrome. Arch Facial Plast Surg 2003;5 (6) 503- 510
PubMed
10.
Grunwell  PBrondsted  KHennigsson  G  et al.  A six-centre international study of the outcome of treatment in patients with cleft of the lip and palate: the results of a cross-linguistic investigation of cleft palate speech. Scand J Plast Reconstr Surg Hand Surg 2000;34 (3) 219- 229
PubMed
11.
Awan  S Development of a low-cost nasalance acquisition system. Powell  TWPathologies of Speech and Language. New Orleans, LA International Clinical Phonetics and Linguistics Association1996;211- 217
12.
Hogen Esch  TTDejonckere  PH Objectivating nasality in healthy and velopharyngeal insufficient children with the Nasalance Acquisition System (NasalView): defining minimal required speech tasks assessing normative values for Dutch language. Int J Pediatr Otorhinolaryngol 2004;68 (8) 1039- 1046
PubMed
13.
Orticochea  M Construction of a dynamic muscle sphincter in cleft palates. Plast Reconstr Surg 1968;41 (4) 323- 327
PubMed
14.
Honig  CA Over pharyngoplastiek [dissertation].  Utrecht, the Netherlands University of Utrecht1963;
15.
Golding-Kushner  KJ Speech and language disorders in velo-cardio-facial syndome. Murphy  KCScambler  PJVelo-Cardio-Facial Syndrome. New York, NY Cambridge University Press2005;181- 199
16.
Eliez  SSchmitt  EWhite  C  et al.  Children and adolescents with velocardiofacial syndrome: a volumetric MRI study. Am J Psychiatry 2000;157 (3) 409- 415
PubMed
17.
Chegar  BETatum  SA  IIIMarrinan  EShprintzen  RJ Upper airway asymmetry in velo-cardio-facial syndrome. Int J Pediatr Otorhinolaryngol 2006;70 (8) 1375- 1381
PubMed
18.
Campbell  LEDaly  EToal  F  et al.  Brain and behaviour in children with 22q11.2 deletion syndrome: a volumetric and voxel-based morphometry MRI study. Brain 2006;129 (pt 5) 1218- 1228
PubMed
19.
Ruotolo  RAVeitia  NACorbin  A  et al.  Velopharyngeal anatomy in 22q11.2 deletion syndrome: a three-dimensional cephalometric analysis. Cleft Palate Craniofac J 2006;43 (4) 446- 456
PubMed
20.
Losken  AWilliams  JKBurstein  FDRiski  JE Surgical correction of velopharyngeal insufficiency in children with velocardiofacial syndrome. Plast Reconstr Surg 2006;117 (5) 1493- 1498
PubMed
21.
Mehendale  FVBirch  MJBirkett  LSell  DSommerlad  BC Surgical management of velopharyngeal incompetence in velocardiofacial syndrome. Cleft Palate Craniofac J 2004;41 (2) 124- 135
PubMed
Original Article
November 17, 2008

Outcome of Velopharyngoplasty in Patients With Velocardiofacial Syndrome

Author Affiliations

Author Affiliations: Division of Pediatric Plastic Surgery, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, the Netherlands.

Arch Otolaryngol Head Neck Surg. 2008;134(11):1159-1164. doi:10.1001/archotol.134.11.1159
Abstract

Objective  To compare the outcomes of surgical correction of velopharyngeal insufficiency (VPI) in patients with velocardiofacial syndrome (VCFS) and a non-VCFS group.

Design  Twenty-five patients with VCFS (16 girls and 9 boys) underwent palatal lengthening for VPI between 1986 and 2001. The mean age at surgery was 6.4 years. Revision was defined as the need for secondary sphincter pharyngoplasty as determined by speech investigation, nasal endoscopy, and acoustic nasometry. A comparison was made to a control group made up of a randomized group of patients without VCFS who underwent palatal lengthening for VPI (32 patients: 10 girls and 22 boys).

Setting  Wilhelmina Children's Hospital, a tertiary referral center in Utrecht, the Netheralands.

Patients  A total of 57 patients who underwent palatal lengthening for VPI, 25 with VCFS and 32 without VCFS.

Interventions  Primary surgery consisted of a palatal lengthening technique. If revision was needed, a sphincter pharyngoplasty was carried out.

Main Outcome Measures  Pharyngeal function was assessed using perceptual speech investigation, nasal endoscopy, and acoustic nasometry.

Results  In the VCFS group, 16% of the patients required surgical revision (4 of 25). These patients were slightly older at the time of primary surgery than those who did not require surgical revision (mean age, 6 vs 5.5 years). In the control group, no patients required revision. Preoperative speech analysis showed a more pronounced VPI in the VCFS group than in the control group. Outcomes of endoscopy and speech hypernasality improved significantly more in the control group than in the VCFS group. Improvement in the results of acoustic nasometry did not differ significantly between the 2 groups.

Conclusions  Treatment of VPI using palatal lengthening in children with VCFS is both safe and effective. The discrepancy in improvement between the speech analysis and the nasal endoscopy results within the VCFS group indicates that mechanical improvement does not necessarily correspond to an improvement in speech and emphasizes the complexity of speech disorders found in VCFS.

Hypernasality is a feature of velopharyngeal insufficiency (VPI), the inability to completely close the velopharyngeal port during speech production. Velopharyngeal insufficiency can result from a variety of causes, the most common being an overt or submucous cleft of the secondary palate.1 In patients with a cleft palate, velopharyngeal closure may be impaired by insufficient tissue, insufficient muscular activity, or scar tissue.

If hypernasality persists after primary repair of the cleft palate, a pharyngoplasty can be performed to normalize resonance during speech production. In our hospital, we routinely use a palatal lengthening procedure for patients with VPI.2,3 Palatal lengthening is achieved by pushback with a pharyngeal flap using only mucosal flaps instead of full-thickness mucoperiosteal flaps for the oral lining of the defect.3 When the periosteum and the palatine arteries are preserved, vascularization of the hard palate is maintained and bone is not exposed, thus avoiding potential detrimental scar formation overlying the hard palate, which may affect normal outgrowth of the maxilla. The level of improvement after surgical intervention varies among patients. One of the explanations for this variation is the existence of a comorbid syndromal abnormality such as velocardiofacial syndrome (VCFS).

Velocardiofacial syndrome has also been called DiGeorge syndrome, Shprintzen syndrome, and conotruncal anomaly face syndrome. Velocardiofacial syndrome is an autosomal dominant disorder caused by the 22q11.2 deletion and is also often referred to as 22q11.2 deletion syndrome. The incidence is approximately 1 per 4000 live births.4 It has a highly variable phenotype and manifests with multiple anomalies such as heart malformations, typical facial characteristics, developmental difficulties, a cleft palate, VPI, and a characteristic pattern of hypernasal speech.58 Pharyngeal muscle hypotonia is present in approximately 75% of patients with VCFS, contributing to hypernasality.9

In the present report, our experiences in functional outcomes after palatal lengthening velopharyngoplasty in patients with VCFS are described and compared with those in a group of patients without VCFS who were similarly treated. In addition, the clinical features and preoperative and postoperative speech analyses of patients with and without VCFS are reviewed.

METHODS
DEMOGRAPHICS

Records of the patients who underwent palatal lengthening for VPI in the 1986-2001 period in our hospital were reviewed. The VCFS group consisted of 25 consecutively treated patients, 15 girls and 10 boys, with a mean age of 6.4 years at the time of surgery. The mean follow-up time was 5 years. Comparisons were made with 32 nonsyndromic cases of palatal lengthening surgery to correct hypernasality (14 submucous cleft palates, 5 congenital short vela, 6 cleft palates, 6 unilateral complete clefts, and 1 bilateral complete cleft). The control group was made up of 10 girls and 22 boys with a mean age at the time of surgery of 7.4 years. All 57 patients had undergone fluorescence in situ hybridization testing to either confirm or rule out the presence of the 22q11.2 deletion that causes VCFS.

ANALYSIS OF VELOPHARYNGEAL FUNCTION

All patients underwent preoperative and postoperative testing of velopharyngeal function by a phoniatrician and a speech pathologist. Screening included a perceptual speech investigation, nasal endoscopy, and acoustic nasometry.

Perceptual speech investigation was performed using Eurocleft sentences,10 which are designed so that every sentence contains 2 explosive consonants in the same position in 5 languages, including Dutch. Hypernasality during speech was categorized as “always,” “sometimes,” and “never.”

Nasal endoscopy was performed using a Pentax 2.3-mm flexible endoscope (Pentax Corp, Tokyo, Japan) and documented on videotape. Patients were asked to repeat high- and low-pressure oral- and nasal-loaded speech. Overall velopharyngeal function, including velar elevation, lateral wall movement, and closure pattern, was rated as “always,” “most of the time,” “sometimes,” and “never.”

Acoustic nasometry data were obtained using “Dr. Speech for Windows”11 in combination with the NasalView12 instrument. Nasalance scores of nasal and oral sounds were registered both preoperatively and postoperatively.

STATISTICAL ANALYSIS

The results of all investigations were statistically analyzed. For the acoustic nasometry, a paired samples t test and an independent sample t test were used. The results of nasoendoscopy, the hypernasality speech tests, and the velum function tests were analyzed with a Wilcoxon signed rank test and a Mann-Whitney test. For the entire statistic analysis, we used complete result couples. Statistical significance was defined as P < .05.

RESULTS
PRIMARY SUCCESS OF SURGERY

In the VCFS group, 4 of the 25 patients required surgical revision (16%). These patients were slightly older at the time of initial surgery: 5.5 vs 6.0 years. Average time interval to revision was 6.7 years (range, 3-8 years). This delay had a variety of causes, including loss to follow-up (1 patient), reluctance of parents for reoperation (1 patient), and surgeon doubt regarding the efficacy of reoperation in patients with VCFS and poor palatal mobility (2 patients). Revision was performed using a sphincter pharyngoplasty.13,14 This technique yielded a clear anatomic improvement in 3 of the 4 patients (full closure achieved during nasoendoscopy) and an audible improvement in speech; however, speech normalized in only 1 case. The one patient whose speech did not improve after revision showed minimal to absent activity of the velum and pharyngeal wall. In the control group, none of the patients required revision. No cases of sleep apnea were observed in either group.

ANALYSIS OF VELOPHARYNGEAL FUNCTION
Perceptual Speech Analysis

In the VCFS group, 24 of 25 patients were preoperatively determined to always manifest speech hypernasality (96%). The remaining patient was rated as sometimes (Figure 1). Postoperatively, 15 of 25 patients with VCFS did not show a decrease in hypernasality (58%). The remaining 10 showed an audible improvement (42%), but none of them achieved normal speech after the operation.

In the control group, 29 of 32 patients always displayed hypernasal speech preoperatively (91%). The remaining 3 patients sometimes showed hypernasal speech (9%). Twenty-five patients showed improvement postoperatively (78%), and 16 experienced completely normalized speech (50%). Multivariate analysis confirmed the significant improvement in hypernasality after the primary operation in both of the study groups (P = .001 for the VCFS group; P < .001 for the control group) and between the study groups (P ≤ .001).

Nasal Endoscopy

Not all patients cooperated sufficiently to provide complete nasal endoscopy data preoperatively and postoperatively (Figure 2). For statistical analysis, only the complete data couples were used. As a result, the VCFS group was reduced to 16 patients, and the control group to 25 patients. Multivariate analysis demonstrated improvement of nasopharyngeal closure after surgery in both groups (VCFS group, P = .002; control group, P < .001) and between the VCFS and non-VCFS groups (P < .01).

Acoustic Nasometry

In the VCFS group, 10 patients were tested preoperatively and postoperatively with acoustic nasometry. In the control group, 28 patients were tested. There was significant improvement in both groups (standard text, P < .01 and denasal text, P < .001 for both groups) (Table). An independent samples t test comparing the degree of improvement between the VCFS and non-VCFS groups demonstrated no significant difference.

COMMENT

Speech and language problems are among the most common characteristics of VCFS.15 The treatment of VPI in patients with VCFS is particularly challenging. Children with VCFS have several intrinsic anatomic and physiologic characteristics that may influence velopharyngeal closure. In addition to the cleft palate, several factors may influence VPI: pharyngeal hypotonia, platybasia (resulting in an increased distance from the palate to the posterior pharyngeal wall), unilateral vocal fold paralysis, and adenoid hypoplasia. With the palatal lengthening procedure used in our hospital, speech evaluation and analysis showed a satisfactory result in 84% of patients with VCFS. After revision, all but 1 patient showed further improvement in speech. All patients in the control group demonstrated improvement in speech, and none required revision.

Golding-Kushner15 suggests that communication skills in children with VCFS may be syndrome specific. Nearly 98% of patients with VCFS have developmental delay.15 When compared with the patients in our control group, the patients with VCFS had trouble cooperating with and completing the different preoperative and postoperative tests, reducing the available complete data scores. This seems to be inherent in the psychosocial development and personality characteristics of patients with VCFS.

This discrepancy in revision rate in our study may be explained by the fact that the VCFS group had more pronounced VPI preoperatively. The results of speech evaluations and nasal endoscopy demonstrated significant discrepancies between VCFS and controls. Both before and after surgery, patients without VCFS performed better. Postoperatively, the control group showed better velopharyngeal closure, decreased hypernasality, and improved velum function compared with the VCFS group. Our nasometry numbers indicate that the degree of improvement did not differ significantly between groups, but because the severity of the hypernasality was more pronounced in the VCFS group, the improvement was often not enough to fully alleviate VPI in the VCFS group. Therefore, a mechanical improvement in the VCFS group may not result in normalization of speech.

Functional brain imaging has provided insight into and illustrated the complexity of the abnormal neurologic mechanisms underlying the mathematic and speech problems seen in VCFS.16 In VCFS, many other factors are presumed to play a role in the outcome after surgery, including abnormal levator muscle anatomy, abnormal dimensions of the oropharynx, abnormal brain development, and psychosocial disorders.9,1719 Reoperation rate was low, although most patients with VCFS did not achieve normal speech by the time of postoperative measurement. Nonetheless, the final outcome is sufficient for children to attend school and have good social contacts. We monitor both of these parameters closely, and school and/or social problems due to incomprehensible speech are an indication to perform additional surgery in children with VCFS in our unit.

In our experience, the beneficial effects of speech-correcting surgery in the VCFS population are best evaluated 1 year after velopharyngoplasty. Patients with VCFS generally need such a time period to adjust and correct their speech pattern and techniques. In our experience, this adjustment to the new anatomic situation after surgery is markedly slower than that experienced by patients without VCFS. At present, we can only speculate about the cause of this slower adjustment. The lower average intelligence of the VCFS population compared with a normal population is a possible factor of importance. One of the limitations of our study was that patients were not matched for intelligence quotient. However, other studies do not mention the slower adjustment in the VCFS population.20 In the future, we intend to report on the long-term effects of palatal lengthening on speech in patients with VCFS. Good prospective randomized studies will be required to get the final answer.

An important benefit of the palatal lengthening technique as used in our hospital is the fact that a sphincter pharyngoplasty can still be carried out if the initial result is unsatisfactory, an especially important consideration in cases of asymmetry, as reported in patients with VCFS,21 when a unilateral or bilateral sphincter pharyngoplasty could further improve speech. In 4 of the 25 patients in our VCFS group, reoperation was required (16%). A 16% revision rate compares favorably with the results of Losken et al,20 who compared the results of sphincter pharyngoplasty for the treatment of VPI in patients with VCFS and a control group without VCFS, similar to our report. They found, as we did, that patients with VCFS had significantly less favorable results and a relatively high revision rate of 22%. However, the data collection in their study was different from that in ours, precluding a detailed comparison between outcomes.

In 2004, Mehendale et al21 also reported on the management of VPI in patients with VCFS. Their study lacks the comparison with a control group. They advocate a staged approach, repairing and retropositioning the muscle first in cases of anterior levators or submucous cleft palate. If this procedure yields insufficient effect, a Hynes pharyngoplasty is carried out. It is evident from their study that normal speech cannot always be achieved in patients with VCFS, even after a staged procedure.

Our study has several shortcomings. It is a retrospective study and includes several limitations such as possible loss of patients for follow-up, selection bias, and our inability to adequately control for additional variables. The intent of our analysis was to evaluate our surgery method and investigate whether this is a safe and reliable method to improve speech problems in VCFS. Formulating a hard conclusion from our results is further hampered by the fact that outcome of VPI surgery generally is not measured and reported in a uniform way, which makes comparisons between studies very difficult if not impossible. The relatively scarce literature reporting outcomes of VPI surgery in the VCFS population shares the same limitation. Based on the available data, we conclude that a palatal lengthening procedure to treat VPI in patients with VCFS is as successful as any other technique reported. The procedure is certainly safe, and it has the advantage that a sphincter pharyngoplasty (Orticochea or Hynes technique) is still possible. In this aspect, our approach resembles that of others like Mehendale et al21 in the treatment of patients VCFS: it proceeds incrementally and does not close off additional surgical options, should the need arise, to achieve an optimal result in the treatment of VPI.

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Article Information

Correspondence: Josine C. C. Widdershoven, MD, University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, the Netherlands (josine.widdershoven@mumc.nl).

Submitted for Publication: September 5, 2007; final revision received January 23, 2008; accepted February 20, 2008.

Author Contributions: Drs Widdershoven and MinkvanderMolen had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Widdershoven, Stubenitsky, and MinkvanderMolen. Analysis and interpretation of data: Widdershoven, Stubenitsky, Breugem, and MinkvanderMolen. Drafting of the manuscript: Widdershoven and Stubenitsky. Critical revision of the manuscript for important intellectual content: Widdershoven, Breugem, and MinkvanderMolen. Statistical analysis: Widdershoven. Study supervision: Breugem and MinkvanderMolen.

Financial Disclosure: None reported.

References
1.
Willging  JPCotton  RT Velopharyngeal insufficiency. Bluestone  CDPediatric Otolaryngology. Vol 2. Philadelphia, PA Saunders2002;1789- 1800
2.
Haapanen  ML Nasalance scores in patients with a modified Honig velopharyngeal flap before and after operation. Scand J Plast Reconstr Surg Hand Surg 1992;26 (3) 301- 305
PubMed
3.
Mink van der Molen  ABJanssen  KSpecken  TFStubenitsky  BM The modified Honig velopharyngoplasty: a new technique to treat hypernasality by palatal lengthening [published online February 1, 2008]. J Plast Reconstr Aesthet Surg
PubMed10.1016/jobjps.2007.12.023
4.
Devriendt  KFryns  JPMortier  Gvan Thienen  MNKeymolen  K The annual incidence of DiGeorge/velocardiofacial syndrome. J Med Genet 1998;35 (9) 789- 790
PubMed
5.
Shprintzen  RJGoldenberg  RBLewin  ML  et al.  A new syndrome involving cleft palate, cardiac anomalies, typical facies, and learning disabilities: velo-cardio-facial syndrome. Cleft Palate J 1978;15 (1) 56- 62
PubMed
6.
Meinecke  PBeemer  FASchinzel  AKushnick  T The velo-cardio-facial (Shprintzen) syndrome. Eur J Pediatr 1986;145 (6) 539- 544
PubMed
7.
Lipson  AHYuille  DAngel  MThompson  PGVandervoord  JGBeckenham  EJ Velocardiofacial syndrome: an important syndrome for the dysmorphologist to recognize. J Med Genet 1991;28 (9) 596- 604
PubMed
8.
Goldberg  RMotzkin  BMarion  RScambler  PJShprintzen  RJ Velo-cadio-facial syndrome: a review of 120 patients. Am J Med Genet 1993;45 (3) 313- 319
PubMed
9.
Zim  SSchelper  RKellman  RTatum  SPloutz-Snyder  RShprintzen  R Thickness and histological and histochemical properties of the superior pharyngeal constrictor muscle in velocardiofacial syndrome. Arch Facial Plast Surg 2003;5 (6) 503- 510
PubMed
10.
Grunwell  PBrondsted  KHennigsson  G  et al.  A six-centre international study of the outcome of treatment in patients with cleft of the lip and palate: the results of a cross-linguistic investigation of cleft palate speech. Scand J Plast Reconstr Surg Hand Surg 2000;34 (3) 219- 229
PubMed
11.
Awan  S Development of a low-cost nasalance acquisition system. Powell  TWPathologies of Speech and Language. New Orleans, LA International Clinical Phonetics and Linguistics Association1996;211- 217
12.
Hogen Esch  TTDejonckere  PH Objectivating nasality in healthy and velopharyngeal insufficient children with the Nasalance Acquisition System (NasalView): defining minimal required speech tasks assessing normative values for Dutch language. Int J Pediatr Otorhinolaryngol 2004;68 (8) 1039- 1046
PubMed
13.
Orticochea  M Construction of a dynamic muscle sphincter in cleft palates. Plast Reconstr Surg 1968;41 (4) 323- 327
PubMed
14.
Honig  CA Over pharyngoplastiek [dissertation].  Utrecht, the Netherlands University of Utrecht1963;
15.
Golding-Kushner  KJ Speech and language disorders in velo-cardio-facial syndome. Murphy  KCScambler  PJVelo-Cardio-Facial Syndrome. New York, NY Cambridge University Press2005;181- 199
16.
Eliez  SSchmitt  EWhite  C  et al.  Children and adolescents with velocardiofacial syndrome: a volumetric MRI study. Am J Psychiatry 2000;157 (3) 409- 415
PubMed
17.
Chegar  BETatum  SA  IIIMarrinan  EShprintzen  RJ Upper airway asymmetry in velo-cardio-facial syndrome. Int J Pediatr Otorhinolaryngol 2006;70 (8) 1375- 1381
PubMed
18.
Campbell  LEDaly  EToal  F  et al.  Brain and behaviour in children with 22q11.2 deletion syndrome: a volumetric and voxel-based morphometry MRI study. Brain 2006;129 (pt 5) 1218- 1228
PubMed
19.
Ruotolo  RAVeitia  NACorbin  A  et al.  Velopharyngeal anatomy in 22q11.2 deletion syndrome: a three-dimensional cephalometric analysis. Cleft Palate Craniofac J 2006;43 (4) 446- 456
PubMed
20.
Losken  AWilliams  JKBurstein  FDRiski  JE Surgical correction of velopharyngeal insufficiency in children with velocardiofacial syndrome. Plast Reconstr Surg 2006;117 (5) 1493- 1498
PubMed
21.
Mehendale  FVBirch  MJBirkett  LSell  DSommerlad  BC Surgical management of velopharyngeal incompetence in velocardiofacial syndrome. Cleft Palate Craniofac J 2004;41 (2) 124- 135
PubMed
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