- Email: [email protected]
Surgical treatment of macroglossia in patients with Beckwith–Wiedemann syndrome: a 20-year experience and review of the literature
Int. J. Oral Maxillofac. Surg. 2012; 41: 300–308 doi:10.1016/j.ijom.2011.10.021, available online at http://www.sciencedirect.com
Clinical Paper Congenital Craniofacial Deformities
Surgical treatment of macroglossia in patients with Beckwith–Wiedemann syndrome: a 20-year experience and review of the literature
D. J. M. Kadouch1, S. M. Maas2, L. Dubois3, C. M. A. M. van der Horst1 1
Department of Plastic and Reconstructive Surgery, Academic Medical Center, Amsterdam, The Netherlands; 2Department of Pediatrics, Academic Medical Center, Amsterdam, The Netherlands; 3Department of Oral and Maxillofacial Surgery, Academic Medical Center, Amsterdam, The Netherlands
D. J. M. Kadouch, S. M. Maas, L. Dubois, C. M. A. M. van der Horst: Surgical treatment of macroglossia in patients with Beckwith–Wiedemann syndrome: a 20-year experience and review of the literature. Int. J. Oral Maxillofac. Surg. 2012; 41: 300– 308. # 2011 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved. Abstract. Macroglossia is observed in the majority of paediatric patients diagnosed with Beckwith–Wiedemann syndrome and surgical treatment may be indicated. A 20-year retrospective study was performed to evaluate all patients with Beckwith– Wiedemann syndrome who underwent tongue reduction surgery at the authors’ institution. A literature review was performed. Surgical treatment was indicated and carried out in 23 patients with a yearly average varying from 0 to 3 subjects. The mean follow-up time was 7 years. Primary indications for surgical treatment of macroglossia included significant tongue protrusion in 30% (n = 7), and a combination of clinical problems in 70% (n = 16). In all cases, the procedure was performed by the same surgeon using an anterior, V-shaped, wedge resection technique. Two patients had direct postoperative complications. No recurrence of macroglossia was observed in this study. Reported clinical outcome during followup demonstrated a satisfactory resting tongue position in all patients. Review of the literature demonstrated variability in surgical indications and techniques, and postoperative outcome. The results of this study indicate that the anterior wedge resection is a simple, effective and safe technique in the surgical treatment of paediatric patients, diagnosed with Beckwith–Wiedemann syndrome, suffering from macroglossia.
0901-5027/030300 + 09 $36.00/0
Accepted for publication 20 October 2011 Available online 21 November 2011
# 2011 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Macroglossia in Beckwith-Wiedemann syndrome Beckwith–Wiedemann syndrome (BWS) is the most well-known paediatric overgrowth disorder5 and has an estimated incidence of 1 in 12,000 to 1 in 13,700 live births13,45,47. The true birth prevalence is thought to be even higher due to milder, unrecognized clinical presentations3,30. The clinical diagnosis of BWS is made using previously designed criteria7,12,44. Differential diagnoses include maternal diabetes gravidarum or obesity and other known genetic overgrowth syndromes such as Simpson– Golabi–Behmel syndrome, Costello syndrome, Perlman syndrome, Sotos syndrome, and mucopolysaccaridosis type VI (Maroteaux–Lamy syndrome)46. Facial features commonly seen in BWS include facial naevus flammeus, midfacial hypoplasia, macroglossia, increased lower face length with a prominent mandible, anterior earlobe creases and posterior helical pits4. Genetic analysis reveals an aberrant imprinting in either one or both imprinted clusters H19 or Lit1 in the majority of patients (80%)1. Aberrant methylation of both imprinted clusters is, in most cases due to a paternal UniParental Disomy (UPD) of the 11p15 region (20% of BWS cases)1. Another, less common, cause of BWS is mutations in the CDKN1C gene. These are found in approximately 5–10% of (mostly familial) cases. With 80% of patients showing abnormal imprinting and 5–10% of patients carrying a mutation in CDKN1C, a group of 10–15% of cases remains without molecular confirmation of the syndrome1. The association between embryonic malignancies and BWS has been well documented, with most of the tumours occurring in the first 4 years of life8,36. Macroglossia is defined as a resting tongue that protrudes beyond the teeth or alveolar ridge41,43. Owing to the highly variable clinical presentation of BWS, macroglossia remains the most consistent symptom, and is seen in 80–99% of patients (Fig. 1)14,35. Tongue reduction procedures are often performed in BWS patients when macroglossia causes one or more of the following problems10,27,28: functional deficits, such as airway obstruction, deglutition, drooling, and phonation difficulties; oro-facial alterations from excessive action of the tongue on the surrounding structures, such as the increase of the gonial angle and of the anterior facial high with anterior open-bite development, and diastema; and abnormal physical appearance of the patient, with lingual protrusion, dyslalia, and drooling, giving the false impression of mental deficiency. Numerous surgical techniques have
Fig. 1. Macroglossia in BWS, including a hemihypertrophy of the right side of the tongue.
been developed for the treatment of macroglossia6,9,11,16,17,21,29,42. The purpose of this report is to present the authors’ experience with paediatric patients diagnosed with BWS that have been surgically treated for macroglossia at their institute during the last two decades. A comparative literature review has been carried out regarding the preoperative clinical indication, perioperative technique and postoperative outcome after surgery of the tongue in BWS patients. Materials and methods
A retrospective chart review was conducted including all patients with BWS who underwent surgical tongue reduction between 1990 and 2010 at the Academic Medical Center (AMC) in Amsterdam, The Netherlands. Inclusion criteria were a diagnosis of BWS, surgical treatment of macroglossia, and minimum follow-up of 1 year. The medical record of each patient was retrieved from the archive and studied in detail. For all surgical procedures performed, the following parameters were evaluated: gender; genetic subtype of BWS; complete or hemi-hypertrophic enlargement of the tongue; sleep-apnea related problems; indication(s) for tongue surgery, such as functional deficits (airway obstruction, feeding problems, persistent drooling, or phonation difficulties), orofacial alterations (mandibular overgrowth with subsequent Class III malocclusion, or diastema), and anticipated problems in appearance (dyslalia, or lingual protrusion); age at time of surgery; type of operation (primary or recurrent); operation time; peri-operative blood loss; additional other craniofacial surgery; postoperative complications; follow-up time; and reported outcome after surgery of the tongue.
301
Regarding the surgical procedure, a Vshaped wedge was excised from the anterior tongue under general anaesthesia. Briefly, tongue marking begins anterolaterally before intra-lingual infiltration with adrenaline 1:200,000 and lidocaine 1%. Two straight lines extended posteromedially to meet the posterior tongue in a varying sharp angle approaching, thus forming a distinctive individual V-shape wedge pattern (Fig. 2). Satinsky clamps were placed lateral to the planned excision. A 15-blade scalpel was used to incise and dissect along the marked line, and excessive lingual tissue was resected using electrocautery. After intra-operative bleeding was controlled, closure was achieved in multiple layers with intramuscular 4-0 Vicryl sutures (Ethicon, Inc., Somerville, NJ, USA). Additional interrupted transmucosal 5-0 Vicryl sutures (Ethicon, Inc., Somerville, NJ, USA) were placed in both palatal and oral sides of the tongue. Postoperatively, close monitoring was recommended because of anticipated airway and feeding concerns. Patients were placed in an anti-Trendelenburg position, received intra-oral cooling with cold packs and were initially admitted to the Pediatric Intensive Care Unit for observation. Since no problems were encountered during the first part of the study period, the postoperative protocol was subsequently adjusted and patients were admitted directly to the regular paediatric ward. A computerized literature search was conducted to identify all relevant clinical studies evaluating the surgical treatment of macroglossia in patients with BWS, published in English, French, German or Dutch. Medline and Embase databases were systematically searched using relevant combinations of the following MESH headings and keywords: Beckwith–Wiedemann, macroglossia, surgery, tongue reduction, (partial) glossectomy. Small (single or double) case reports, letters, animal studies, and studies evaluating macroglossia lacking an association with BWS were excluded from the search. All relevant articles were used as additional sources of primary papers by crosschecking the reference sections with the master list of compiled articles. The crossreferencing process of locating other studies was continued until no further articles were generated. Results
From 1990 to 2010, 54 BWS patients presented at the authors’ craniofacial outpatient clinic with medical problems related to macroglossia. Conservative management
302
Kadouch et al. surgery after insufficient tissue removal at primary reduction. No recurrence of macroglossia was observed. Direct postoperative complications were seen in 2 cases (8%): one patient had postoperative airway obstruction after incorrect perioperative morphine administration (4%) and another suffered from partial wound dehiscence after 3 days (4%). No intubation problems were encountered. The average follow-up time was 7 years (range 1–19 years). Reported clinical outcome during follow-up demonstrated a satisfactory resting tongue position in all 23 surgically treated patients, defined as a tongue that lies within the alveolar ridge borders of the oral cavity for more than 95% of the time (Fig. 3). Persistent orofacial growth disturbance was present in one subject (4%) after 6 years. Speech problems were observed in one child (4%) with a general developmental delay caused by comorbidity. Complications of lingual nerve dysfunction were not observed in the study group. Literature study
Fig. 2. Anterior wedge resection technique as performed at the Academic Medical Center of Amsterdam. Illustrations by Serge A. Steenen.
of macroglossia was indicated in 31 patients with mild symptoms of macroglossia. Surgical treatment was indicated and performed in 23 patients with a yearly average varying from 0 to 3 subjects. In all cases, the senior author (C.M.A.M. vdH) performed the tongue reduction surgery using the anterior, V-shaped, wedge resection (AWR) technique. Patient demographics are shown in Table 1. There were 12 males and 11 females. Routine analysis of blood samples resulted in the following genetic subtype distribution: aberrant imprinting of Lit1 gene in 48%, aberrant imprinting of H19 gene in 13%, and UPD in 26%. In three subjects (13%), no molecular confirmation was found. Hemi-hypertrophic asymmetry of the tongue was observed in 30%, with the right greater than the left in 22% and the left greater than the right in 8% of the cases. Preoperative polysomnographic
investigation for suspected sleep-apnea related problems was performed in 5 patients (22%). In most cases (70%), the indication for tongue reduction surgery was based on a combination of significant tongue protrusion and other clinical problems related to the macroglossia such as feeding problems (39%), persistent drooling (35%), and swallowing difficulties (13%). Primary surgical indications, based on a solitary tongue protrusion (with subsequent anticipated problems in appearance), was reported in 7 cases (30%). All included patients underwent primary tongue surgery with a mean age of 19 months (range 3–68 months). Mean operation time was 29 min. Blood loss was not significant. Nine patients (39%) underwent other, additional procedures, including lingual frenulectomy in 5 patients (22%) and adenotonsillectomy in 4 patients (17%). One subject had secondary tongue
10 publications were identified18,19,22,25,27,33,34,37–39, describing 94 BWS subjects who underwent tongue reduction surgery. Here the authors review only the aspects of the papers that deal with the indications, the surgical techniques that were used for the correction of the macroglossia, and, if reported, the long-term outcome after surgery (Table 2). The number of patients who underwent tongue reduction surgery ranged from n = 322 to n = 17 patients39. The main indications prior to surgery were reported in only 7 studies, and varied from solitary tongue protrusion to multiple clinical problems such as drooling, speech developmental delay, and dental malocclusion18,19,22,27,33,34,37. The mean age at surgery ranged from 15 to 51 months. In the majority of the reported cases the AWR technique was performed for reduction of the tongue. Preoperative tracheostomies were reported in four cases19,33. Postoperative complications were mentioned in 4 of the 10 studies, and included wound dehiscence (n = 2)19, and recurrence of macroglossia (n = 4)18,19,22. Reports on clinical outcomes after tongue reduction surgery varied and were subjective. Discussion
In BWS, macroglossia is typically present at birth and may require surgical intervention in a small percentage of patients. To the best of the authors’ knowledge, this
Macroglossia in Beckwith-Wiedemann syndrome Table 1. Patient demographic and clinical data regarding tongue surgery at the Academic Medical Center of Amsterdam between 1990 and 2010. Characteristics
All patients n = 23
Gender Male/female Genetic subtype of BWS Aberrant imprinting Lit1 Aberrant imprinting H19 UPD No molecular confirmation Hemihypertrophy of tongue Right > left Left > right Preoperative polysomnographic registration Primary surgical indication Solitary tongue protrusion Combination of clinical problems Mean age at time of surgery (months) [range] Mean operation time (min) [range] Additional craniofacial interventions Frenuloplasty Adenotonsillectomy Jaw surgery Postoperative complications Airway obstruction Wound dehiscence Recurrence of macroglossia Mean follow-up time (years) [range] Reported clinical outcome Satisfactory resting tongue position Persistent oro-facial maldevelopment Speech problems
study is unique in describing the largest series of BWS patients that were surgically treated for macroglossia. 23 patients with BWS who underwent surgical tongue reduction at the authors’ institution are discussed. All procedures were performed by the same surgeon, using the same AWR technique. The literature pertinent to BWS and the surgical treatment of macroglossia revealed 10 other studies describing a total of 94 subjects. Previous reports regarding the treatment of macrolgossia in BWS have not yet included the underlying genetic component. When comparing the present results with the literature regarding BWS genotypes, a similar genetic subtype distribution is found in about 60% of patients with an aberrant imprinting in one of the imprinted clusters H19 or Lit1, about 20% of patients with a UPD, and about 15% of patients without molecular confirmation of the syndrome1. This may lead to the assumption that the differences in expression and severity of macroglossia are equally distributed over the genetic subgroups of BWS. Tongue function is important for deglutition, phonation, respiration, and to wet the lips. Also, tongue sensory function plays an essential role in the sense of taste. The clinical diagnosis of macroglossia is
n = 12/n = 11
% 100 52/48
n = 11 n=3 n=6 n=3 n=7 n=5 n=2 n=5
48 13 26 13 30 22 8 22
n=7 n = 16
30 70
19 months [3–68] 29 min [18–45] n=9 n=5 n=4 0 n=2 n=1 n=1 0 7 years [1–19] n = 23 n=1 n=1
39 22 17 0 8 4 4 0 100 4 4
made on the basis of subjective criteria by evaluating symptoms such as difficulties concerning respiration and protrusion of the tongue, drooling, phonation, and deglutition6,10. In the authors’ experience with BWS, the enlarged tongue varies in degree and severity. Hemi-hypertrophy was observed in 30% of the study patients. Unilateral enlargement of the tongue in BWS was only addressed in two other studies37,39. Of those, only the sample survey study performed by VAN BORSEL et al.39 noted 2 of their 40 respondents with a hemi-hypertrophic asymmetry of the tongue. In severe cases of macroglossia, the airway may be compromised at birth or later at rest, intermittently, related to position, or during feeding. Both KACKER et al. and RIMELL et al. described cases of severe airway obstruction due to macroglossia and the placement of a preoperative tracheostomy19,33. Acute airway obstruction due to macroglossia was not observed in any of the present patients, therefore no pre-tongue reduction tracheostomy was indicated. Sleep-apnea related problems were found in five of the present patients, who subsequently underwent polysomnographic evaluation. The outcome revealed a varying degree of upper airway resis-
303
tance syndrome in three of the five subjects, without any signs of classic obstructive sleep apnea syndrome. RIMELL et al. also observed milder signs of upper airway in seven of the nine patients who were followed up beyond 18 months of age. They concluded that obstruction in early infancy would be related to enlargement of the tongue base, and that airway obstruction occurring later in childhood most likely results from tonsil and adenoid hypertrophy33. When looking at the surgical indications, the present results were generally comparable with previous studies. Acute airway obstruction was not observed in the authors’ patients, but it was reported to be an important indication in subjects from three other studies18,19,33. Anticipated problem in appearance was a primary indication for tongue reduction surgery in 7 of the present subjects (30%), and played an important role in the indication of the other 17 patients operated on, as well as patients presented by six other studies18,19,27,33,34,37. In the majority of the authors’ cases (70%), the indication for tongue reduction surgery was based on a combination of significant tongue protrusion and functional deficits, such as difficulties in feeding, management of saliva (drooling) and swallowing, seen in 9, 8 and 3 patients, respectively. Similar indications were reported in only one other study performed by TOMLINSON et al.37. Particularly during feeding, the enlarged tongue overlying the teeth may result in repeated injuries of the tongue surface, causing bleeding and pain and eventually impairment of mastication32. Mandibular overgrowth served as an important surgical indication in at least 4 of the 10 other studies19,22,27,33 and was not seen as such in our patient group. This might be explained by the timing of tongue surgery. The aim of glossoplastic surgery is to reduce the size of the tongue, whilst maintaining normal tongue shape and function. A recent study performed by KAWAFUJI et al. demonstrates that untreated macroglossia may result in an anterior open bite and wide dental arch20. The present authors operated on subjects who presented with severe macroglossia with a minimum age of 3 months in an effort to reduce or prevent oro-facial growth disturbances. Late referral caused delayed surgical treatment in 4 cases. This resulted in a mean age at surgery of 19 months in this patient group, compared to a mean age of 29 months calculated from the selected literature review studies.
304
Kadouch et al.
Fig. 3. Facial appearances of BWS patients with macroglossia who underwent tongue reduction surgery at different ages (preoperative:at surgery:postoperative). Patient A, 0.2:0.3:0.4 year; Patient B, 0.6:0.9:1.7 year; Patient C, 0.8:0.9:5.1 years; Patient D, 4.9:5.7:6.5 years; Patient E, 4.3:4.5:7.5 years; Patient F, 0.2:0.8:12.3 years.
Knowledge of the anatomy of the tongue and the position of the lingual nerve is essential to allow safe performance of surgical tongue reduction for the treatment of macroglossia48. Whilst reducing the tongue, it is important to preserve the inferolateral neurovascular bundles and at the same time maintain the tongue shape2,15,23,31,48. Numerous surgical techniques have been developed for the treatment of macroglossia6,9,11,16,17,21,29,42. According to a recent study performed by HETTINGER et al., these procedures can be divided into 1 of 6 categories, including: tip amputations, AWR, central reductions (CR), dorsal flap excisions, marginal excisions (ME), and combination procedures (CP).
The results of the literature study demonstrate that the majority of procedures were performed by removal of tongue tissue in the midline via AWR or CR. Novel techniques also include submucosal removal of tongue tissue26, and tongue reduction using an ultrasonic aspirator49. Current experience with these two innovative methods is limited. In BWS, the tongue is enlarged in three dimensions and involves increased length, width and height of the muscle. Since the macroglossia is not phenotypically homogenous, surgical techniques designed for reducing tongue volume should be individually tailored for each patient19,37. The AWR procedure resulted in shortening of the tongue muscle in length and width (a
shortcoming of the AWR technique is that the tongue height remains unchanged). By varying the angle of the V-wedge, this procedure could be adjusted to both regular and more severe expressions of macroglossia. In case of tongue asymmetry, a larger portion could be excised from the hemihypertrophic side of the tongue. The authors’ mean operation time was 29 min and no problems were encountered during the surgical procedures. Despite the good vascularity of the tongue, blood loss was not significant and peri-operative hemostasis was achieved without difficulties. Postoperative management was mentioned in two studies. Both TOMLINSON et al. and KACKER et al. administered systemic steroids to avoid postoperative oedema of the tongue and monitored all patients in the ICU for possible airway obstruction19,37. The authors did not administer systemic steroids. Since substantial oedema was only located at the anterior tip of the tongue no postoperative airway obstruction was observed. As a consequence, the authors found no need for monitoring in the ICU and patients were directly admitted to the regular paediatric ward. Wound dehiscence, as seen in one of the present patients, was also reported by KACKER et al. and KVEIM et al.19,22. Recurrence of macroglossia as reported in the literature18,19,22, was not observed in the present study group. Multiple variables can affect the longterm outcome after partial glossectomy in a child with BWS. The timing of the intervention, the surgical technique, hearing and cognitive functioning are all known variables in the outcome after surgery of the tongue. In the present study, the reported clinical outcome during follow-up demonstrated a satisfactory resting tongue position in all 23 surgically treated patients after a mean follow-up of 7 years (range 1–19 years). Mandibular overgrowth (with subsequent Class III malocclusion) was present in one patient who was operated on at the age of 18 months, after follow-up of 6 years. In the literature selection, reports on clinical outcomes varied and were subjective. The study performed by TOMLINSON et al.37 was unique in describing long-term outcomes such as speech, tongue mobility, taste sensation and cosmesis after tongue reduction surgery in a detailed manner. They concluded that paediatric patients with BWS, who underwent glossoplastic surgery, are unlikely to have completely normal tongue function and appearance as adults. A small pilot study by MATSUNE et al. demonstrated that taste may decline after surgical reduction of the tongue,
Table 2. Existing data regarding surgical treatment and outcome of macroglossia in BWS. Age at surgery (months)
Surgical technique(s)
(1) Airway obstruction (2) Aesthetic appearance (3) Problems in speech
12–168 (mean 51)
CR (single or double stellate)
*Persistent macroglossia (n = 2)
No complaints of abnormal taste or sensation
Disproportionate tongue bulk (91%), abnormal tongue appearance (82%), specific speech sounds errors (73%), and short tongue tip (55%) Good speech and oral-motor outcome (70%)
Post-operative complications
Year
HETTINGER et al.18
2011
7
TOMLINSON et al.37
2007
11
(1) Tongue protrusion (2) Failure of oral competence (3) Persistent drooling
4–39 (mean 15)
AWR (sometimes with excised central tongue)
NM
SHIPSTER et al.34
2006
10
(1) Varying degrees of constant tongue protrusion
1–60 (mean 32)
AWR, CR (keyhole excision)
NM
MATSUNE et al.25
2005
4
NM
36–60 (mean 39)
AWR, CR
NM
Salty and bitter taste significantly declined in central tongue
KACKER et al.19
2000
4
(1) Airway obstruction (2) Varying degrees of tongue protrusion (3) Problems in speech (4) Cass III malocclusion
3–48 (mean 26)
CR (keyhole excision)
Tongue protrusion successfully treated in 3 out of 4 patients (75%)
VAN BORSEL et al.39
2000
17
NM
3–60 (mean 17)
AWR, CR, ME, CP
*Wound dehiscence (n = 2), *Persistent macroglossia (n = 1), *Preoperative tracheostomy (n = 2) None
RIMELL et al.33
1995
9
(1) (2) (3) (4) (5)
NM
AWR
Main indication(s)
Airway obstruction Aesthetic appearance Problems in speech Cass III malocclusion Dental caries
*Preoperative tracheostomy (n = 2)
Clinical outcome
Persistent articulation problems after tongue surgery (12%) Satisfactory resting tongue position in at least 3 operated subjects (33%)
Comments by author Retrospective chart review of 7 patients that underwent either a single stellate (n = 4) or a double stellate central (n = 3) tongue reduction Solitary detailed report on long-term outcome assessed by questionnaires (n = 11). Additional formal medical and speech pathology assessment in 4 patients Systematic investigation of oral motor skills and speech production preand post-tongue reductions surgery Study on taste after tongue reduction surgery, performed by impregnated filter papers compared to normal Japanese children Results of small series using keyhole technique
Sample survey study on relation between macroglossia and speech Airway obstruction during childhood might also be related to tonsillar and adenoid hypertrophy
Macroglossia in Beckwith-Wiedemann syndrome
Author
Operated subjects, N
305
Macroglossia should be treated symptomatically, no need for prophylactic resection
NM, not mentioned; AWR, anterior wedge resection; CR, central reduction; ME, marginal excision; CP, combination procedures.
NM AWR 3–36 (1) Varying degrees of tongue protrusion (2) Problems in speech (3) Cass III malocclusion MCMANAMNY et al.27
1985
16
AWR (1) Mandibular overgrowth (2) Cass III malocclusion KVEIM et al.22
1985
3
3–96 (mean 28)
*Wound dehiscence (n = 1) *Regrowth of the tongue (n = 1) NM
Persistent dental deformities (33%)
Reduction glossoplasty should be considered very early to prevent maxillofacial deformities and to ensure optimal cosmetic and functional outcome Prevention of dental deformity should assume greater priority Satisfactory results in both maxillofacial growth as well as cosmesis (100%) NM CR (single stellate excision) NM NM
Clinical outcome Year Author
13
Post-operative complications Surgical technique(s) Main indication(s)
Age at surgery (months) Operated subjects, N Table 2 (Continued )
1994
Comments by author
Kadouch et al.
VASQUEZ et al.38
306
they used impregnated filter papers with different flavours and compared operated BWS children to normal Japanese children25. In the present study group, no cases of lingual nerve dysfunction were observed during follow-up. It would be meaningful to investigate the taste in operated patients using a validated test. Speech improvement has also been reported as a result of tongue reduction24. Speech outcome after tongue surgery may affect sounds made primarily by the tip of the tongue against the upper or lower teeth or the anterior palate. In the study performed by VAN BORSEL et al., BWS patients with macroglossia were reported to have articulation problems, some of which persisted after corrective tongue surgery (mean age 1.4 years; range 3– 60 months) using different operative techniques39. Another retrospective study performed by SHIPSTER et al. found distinct speech errors caused by macroglossia that were subsequently eliminated by surgical tongue reduction using the anterior wedge resection or the ‘keyhole’ technique34. Speech problems were observed in one of the authors’ patients with a general developmental delay caused by comorbidity. No other specific speech problems were reported in the present patients; most probably as a result of early surgical intervention (the majority of patients underwent tongue surgery before the age of 2 years) and, if indicated, adjuvant speech therapy. The present results indicate that the AWR is a simple, effective and safe technique in the surgical treatment of paediatric BWS patients suffering from macroglossia. Primary limitations of this study include the retrospective nature of data collection. In order to evaluate the effects of tongue reduction properly, the authors will investigate tongue function, perform a speech assessment, and analyse oro-facial growth, in a multidisciplinary setting with objective and validated methods40. Detailed analyses in a greater number of subjects with BWS may help to evaluate the long-term impact of partial glossectomy further. Funding
None. Competing interests
None. Ethical approval
Not required.
Macroglossia in Beckwith-Wiedemann syndrome Acknowledgement. The authors would like
to thank S.A. Steenen for his illustrative support.
16. 17.
References 1. Bliek J, Maas SM, Ruijter JM, Hennekam RC, Alders M, Westerveld A, Mannens MM. Increased tumour risk for BWS patients correlates with aberrant H19 and not KCNQ1OT1 methylation: occurrence of KCNQ1OT1 hypomethylation in familial cases of BWS. Hum Mol Genet 2001;10:467–76. 2. Bracka A. The blood supply of dorsal tongue flaps. Br J Plast Surg 1981;34:379–84. 3. Chitayat D, Rothchild A, Ling E, Friedman JM, Couch RM, Yong SL, Baldwin VJ, Hall JG. Apparent postnatal onset of some manifestations of the WiedemannBeckwith syndrome. Am J Med Genet 1990;36:434–9. 4. Cohen Jr MM. Overgrowth syndromes: an update. Adv Pediatr 1999;46:441–91. 5. Cohen Jr MM. Beckwith–Wiedemann syndrome: historical, clinicopathological, and etiopathogenetic perspectives. Pediatr Dev Pathol 2005;8:287–304. 6. Davalbhakta A, Lamberty BG. Technique for uniform reduction of macroglossia. Br J Plast Surg 2000;53:294–7. 7. DeBaun MR, Tucker MA. Risk of cancer during the first four years of life in children from The Beckwith–Wiedemann Syndrome Registry. J Pediatr 1998;132:398– 400. 8. DeBaun MR, Siegel MJ, Choyke PL. Nephromegaly in infancy and early childhood: a risk factor for Wilms tumor in Beckwith–Wiedemann syndrome. J Pediatr 1998;132:401–4. 9. Dingman RO, Grabb WC. Lymphangioma of the tongue. Plast Reconstr Surg Transplant Bull 1961;27:214–23. 10. Dios PD, Posse JL, Sanroman JF, Garcia EV. Treatment of macroglossia in a child with Beckwith–Wiedemann syndrome. J Oral Maxillofac Surg 2000;58:1058–61. 11. Egyedi P. Reduction of tongue size in the surgical correction of jaw deformity. Br J Oral Surg 1965;3:13–21. 12. Elliott M, Bayly R, Cole T, Temple IK, Maher ER. Clinical features and natural history of Beckwith–Wiedemann syndrome: presentation of 74 new cases. Clin Genet 1994;46:168–74. 13. Engstrom W, Lindham S, Schofield P. Wiedemann-Beckwith syndrome. Eur J Pediatr 1988;147:450–7. 14. Filippi G, McKusick VA. The Beckwith– Wiedemann syndrome. Medicine (Baltimore) 1970;49:279–98. 15. Gasparini G, Saltarel A, Carboni A, Maggiulli F, Becelli R. Surgical management of macroglossia: discussion of 7 cases.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002;94:566–71. Gupta OP. Congenital macroglossia. Arch Otolaryngol 1971;93:378–83. Harada K, Enomoto S. A new method of tongue reduction for macroglossia. J Oral Maxillofac Surg 1995;53:91–2. Hettinger PC, Denny AD. Double stellate tongue reduction: a new method of treatment for macroglossia in patients with Beckwith– Wiedemann syndrome. Ann Plast Surg 2011;67:240–4. Kacker A, Honrado C, Martin D, Ward R. Tongue reduction in Beckwith–Wiedemann syndrome. Int J Pediatr Otorhinolaryngol 2000;53:1–7. Kawafuji A, Suda N, Ichikawa N, Kakara S, Suzuki T, Baba Y, Ogawa T, Tsuji M, Moriyama K. Systemic and maxillofacial characteristics of patients with Beckwith– Wiedemann syndrome not treated with glossectomy. Am J Orthod Dentofacial Orthop 2011;139:517–25. Kole H. Results, experience and problems in the surgical treatment of anomalies with reverse overbite. Int J Oral Surg 1965;19:427–50. Kveim M, Fisher JC, Jones KL, Gruer B. Early tongue resection for Beckwith–Wiedemann macroglossia. Ann Plast Surg 1985;14:142–4. Lauretano AM, Li KK, Caradonna DS, Khosta RK, Fried MP. Anatomic location of the tongue base neurovascular bundle. Laryngoscope 1997;107:1057–9. Massengill R, Pickrell K. Surgical correction of macroglossia. Pediatrics 1978; 61:485–8. Matsune K, Miyoshi K, Kosaki R, Ohashi H, Maeda T. Taste after reduction of the tongue in Beckwith–Wiedemann syndrome. Br J Oral Maxillofac Surg 2006;44:49–51. Maturo SC, Mair EA. Submucosal minimally invasive lingual excision: an effective, novel surgery for pediatric tongue base reduction. Ann Otol Rhinol Laryngol 2006;115:624–30. McManamny DS, Barnett JS. Macroglossia as a presentation of the Beckwith–Wiedemann syndrome. Plast Reconstr Surg 1985;75:170–6. Menard RM, Delaire J, Schendel SA. Treatment of the craniofacial complications of Beckwith–Wiedemann syndrome. Plast Reconstr Surg 1995;96:27–33. Mixter RC, Ewanowski SJ, Carson LV. Central tongue reduction for macroglossia. Plast Reconstr Surg 1993;91:1159–62. Moore ES, Ward RE, Escobar LF, Carlin ME. Heterogeneity in Wiedemann-Beckwith syndrome: anthropometric evidence. Am J Med Genet 2000;90:283–90. Morgan WE, Friedman EM, Duncan NO, Sulek M. Surgical management of macroglossia in children. Arch Otolaryngol Head Neck Surg 1996;122:326–9.
307
32. Perkins JA. Overview of macroglossia and its treatment. Curr Opin Otolaryngol Head Neck Surg 2009;17:460–5. 33. Rimell FL, Shapiro AM, Shoemaker DL, Kenna MA. Head and neck manifestations of Beckwith–Wiedemann syndrome. Otolaryngol Head Neck Surg 1995;113: 262–5. 34. Shipster C, Oliver B, Morgan A. Speech and oral motor skills in children with Beckwith Wiedemann Syndrome: pre- and post-tongue reduction surgery. Adv Speech Lang Pathol 2006;8:45–55. 35. Sotelo-Avila C, Gonzalez-Crussi F, Fowler JW. Complete and incomplete forms of Beckwith–Wiedemann syndrome: their oncogenic potential. J Pediatr 1980;96:47– 50. 36. Tan TY, Amor DJ. Tumour surveillance in Beckwith–Wiedemann syndrome and hemihyperplasia: a critical review of the evidence and suggested guidelines for local practice. J Paediatr Child Health 2006;42:486–90. 37. Tomlinson JK, Morse SA, Bernard SP, Greensmith AL, Meara JG. Long-term outcomes of surgical tongue reduction in Beckwith–Wiedemann syndrome. Plast Reconstr Surg 2007;119:992–1002. 38. Vasquez CV, Buis J, Schneid H, Martinez H, Le Bouc Y. Macroglossie congenitale et syndrome de Wiedemann-Beckwith. Ann Pediatr (Paris) 1994;41:303–15. 39. Van Borsel J, Van Snick K, Leroy J. Macroglossia and speech in Beckwith– Wiedemann syndrome: a sample survey study. Int J Lang Commun Disord 1999; 34:209–21. 40. van der Horst CM, Smeulders MJ, Polsbroek RM, Ravesloot JH. Development of a test for evaluation of taste perception after tongue reduction. J Craniomaxillofac Surg 2011; 38:452–4. 41. Vogel JE, Mulliken JB, Kaban LB. Macroglossia: a review of the condition and a new classification. Plast Reconstr Surg 1986;78:715–23. 42. Wang J, Goodger NM, Pogrel MA. The role of tongue reduction. Oral Surg Oral Med Pathol Oral Radiol Endod Oral 2003;95:269–73. 43. Weiss LS, White JA. Macroglossia: a review. J La State Med Soc 1990; 142:13–6. 44. Weksberg R, Nishikawa J, Caluseriu O, Fei YL, Shuman C, Wei C, Steele L, Cameron J, Smith A, Ambus I, Li M, Ray PN, Sadowski P, Squire J. Tumor development in the Beckwith–Wiedemann syndrome is associated with a variety of constitutional molecular 11p15 alterations including imprinting defects of KCNQ1OT1. Hum Mol Genet 2001;10:2989–3000. 45. Weksberg R, Shuman C, Smith AC. Beckwith–Wiedemann syndrome. Am J Med Genet C Semin Med Genet 2005;137C:12– 23.
308
Kadouch et al.
46. Weksberg R, Shuman C, Beckwith JB. Beckwith–Wiedemann syndrome. Eur J Hum Genet 2010;18:8–14. 47. Wiedemann HR. Frequency of WiedemannBeckwith syndrome in Germany; rate of hemihyperplasia and of tumours in affected children. Eur J Pediatr 1997;156:251. 48. Yang HM, Woo YJ, Won SY, Kim DH, Hu KS, Kim HJ. Course and distribution of the lingual nerve in the ventral tongue region:
anatomical considerations for frenectomy. J Craniofac Surg 2009;20:1359–63. 49. Yura S, Kato T, Ooi K, Izumiyama Y. Tongue reduction techniques with an ultrasonic surgical aspirator. J Oral Maxillofac Surg 2009;67:1568–71.
Address: Daniel J.M. Kadouch Department of Plastic
Reconstructive and Hand Surgery Academic Medical Center P.O. Box 22660 1100 DD Amsterdam The Netherlands Tel: +31 20 5662974; Fax: +31 20 6917549 E-mail: [email protected]
Clinical Paper Congenital Craniofacial Deformities
Surgical treatment of macroglossia in patients with Beckwith–Wiedemann syndrome: a 20-year experience and review of the literature
D. J. M. Kadouch1, S. M. Maas2, L. Dubois3, C. M. A. M. van der Horst1 1
Department of Plastic and Reconstructive Surgery, Academic Medical Center, Amsterdam, The Netherlands; 2Department of Pediatrics, Academic Medical Center, Amsterdam, The Netherlands; 3Department of Oral and Maxillofacial Surgery, Academic Medical Center, Amsterdam, The Netherlands
D. J. M. Kadouch, S. M. Maas, L. Dubois, C. M. A. M. van der Horst: Surgical treatment of macroglossia in patients with Beckwith–Wiedemann syndrome: a 20-year experience and review of the literature. Int. J. Oral Maxillofac. Surg. 2012; 41: 300– 308. # 2011 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved. Abstract. Macroglossia is observed in the majority of paediatric patients diagnosed with Beckwith–Wiedemann syndrome and surgical treatment may be indicated. A 20-year retrospective study was performed to evaluate all patients with Beckwith– Wiedemann syndrome who underwent tongue reduction surgery at the authors’ institution. A literature review was performed. Surgical treatment was indicated and carried out in 23 patients with a yearly average varying from 0 to 3 subjects. The mean follow-up time was 7 years. Primary indications for surgical treatment of macroglossia included significant tongue protrusion in 30% (n = 7), and a combination of clinical problems in 70% (n = 16). In all cases, the procedure was performed by the same surgeon using an anterior, V-shaped, wedge resection technique. Two patients had direct postoperative complications. No recurrence of macroglossia was observed in this study. Reported clinical outcome during followup demonstrated a satisfactory resting tongue position in all patients. Review of the literature demonstrated variability in surgical indications and techniques, and postoperative outcome. The results of this study indicate that the anterior wedge resection is a simple, effective and safe technique in the surgical treatment of paediatric patients, diagnosed with Beckwith–Wiedemann syndrome, suffering from macroglossia.
0901-5027/030300 + 09 $36.00/0
Accepted for publication 20 October 2011 Available online 21 November 2011
# 2011 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Macroglossia in Beckwith-Wiedemann syndrome Beckwith–Wiedemann syndrome (BWS) is the most well-known paediatric overgrowth disorder5 and has an estimated incidence of 1 in 12,000 to 1 in 13,700 live births13,45,47. The true birth prevalence is thought to be even higher due to milder, unrecognized clinical presentations3,30. The clinical diagnosis of BWS is made using previously designed criteria7,12,44. Differential diagnoses include maternal diabetes gravidarum or obesity and other known genetic overgrowth syndromes such as Simpson– Golabi–Behmel syndrome, Costello syndrome, Perlman syndrome, Sotos syndrome, and mucopolysaccaridosis type VI (Maroteaux–Lamy syndrome)46. Facial features commonly seen in BWS include facial naevus flammeus, midfacial hypoplasia, macroglossia, increased lower face length with a prominent mandible, anterior earlobe creases and posterior helical pits4. Genetic analysis reveals an aberrant imprinting in either one or both imprinted clusters H19 or Lit1 in the majority of patients (80%)1. Aberrant methylation of both imprinted clusters is, in most cases due to a paternal UniParental Disomy (UPD) of the 11p15 region (20% of BWS cases)1. Another, less common, cause of BWS is mutations in the CDKN1C gene. These are found in approximately 5–10% of (mostly familial) cases. With 80% of patients showing abnormal imprinting and 5–10% of patients carrying a mutation in CDKN1C, a group of 10–15% of cases remains without molecular confirmation of the syndrome1. The association between embryonic malignancies and BWS has been well documented, with most of the tumours occurring in the first 4 years of life8,36. Macroglossia is defined as a resting tongue that protrudes beyond the teeth or alveolar ridge41,43. Owing to the highly variable clinical presentation of BWS, macroglossia remains the most consistent symptom, and is seen in 80–99% of patients (Fig. 1)14,35. Tongue reduction procedures are often performed in BWS patients when macroglossia causes one or more of the following problems10,27,28: functional deficits, such as airway obstruction, deglutition, drooling, and phonation difficulties; oro-facial alterations from excessive action of the tongue on the surrounding structures, such as the increase of the gonial angle and of the anterior facial high with anterior open-bite development, and diastema; and abnormal physical appearance of the patient, with lingual protrusion, dyslalia, and drooling, giving the false impression of mental deficiency. Numerous surgical techniques have
Fig. 1. Macroglossia in BWS, including a hemihypertrophy of the right side of the tongue.
been developed for the treatment of macroglossia6,9,11,16,17,21,29,42. The purpose of this report is to present the authors’ experience with paediatric patients diagnosed with BWS that have been surgically treated for macroglossia at their institute during the last two decades. A comparative literature review has been carried out regarding the preoperative clinical indication, perioperative technique and postoperative outcome after surgery of the tongue in BWS patients. Materials and methods
A retrospective chart review was conducted including all patients with BWS who underwent surgical tongue reduction between 1990 and 2010 at the Academic Medical Center (AMC) in Amsterdam, The Netherlands. Inclusion criteria were a diagnosis of BWS, surgical treatment of macroglossia, and minimum follow-up of 1 year. The medical record of each patient was retrieved from the archive and studied in detail. For all surgical procedures performed, the following parameters were evaluated: gender; genetic subtype of BWS; complete or hemi-hypertrophic enlargement of the tongue; sleep-apnea related problems; indication(s) for tongue surgery, such as functional deficits (airway obstruction, feeding problems, persistent drooling, or phonation difficulties), orofacial alterations (mandibular overgrowth with subsequent Class III malocclusion, or diastema), and anticipated problems in appearance (dyslalia, or lingual protrusion); age at time of surgery; type of operation (primary or recurrent); operation time; peri-operative blood loss; additional other craniofacial surgery; postoperative complications; follow-up time; and reported outcome after surgery of the tongue.
301
Regarding the surgical procedure, a Vshaped wedge was excised from the anterior tongue under general anaesthesia. Briefly, tongue marking begins anterolaterally before intra-lingual infiltration with adrenaline 1:200,000 and lidocaine 1%. Two straight lines extended posteromedially to meet the posterior tongue in a varying sharp angle approaching, thus forming a distinctive individual V-shape wedge pattern (Fig. 2). Satinsky clamps were placed lateral to the planned excision. A 15-blade scalpel was used to incise and dissect along the marked line, and excessive lingual tissue was resected using electrocautery. After intra-operative bleeding was controlled, closure was achieved in multiple layers with intramuscular 4-0 Vicryl sutures (Ethicon, Inc., Somerville, NJ, USA). Additional interrupted transmucosal 5-0 Vicryl sutures (Ethicon, Inc., Somerville, NJ, USA) were placed in both palatal and oral sides of the tongue. Postoperatively, close monitoring was recommended because of anticipated airway and feeding concerns. Patients were placed in an anti-Trendelenburg position, received intra-oral cooling with cold packs and were initially admitted to the Pediatric Intensive Care Unit for observation. Since no problems were encountered during the first part of the study period, the postoperative protocol was subsequently adjusted and patients were admitted directly to the regular paediatric ward. A computerized literature search was conducted to identify all relevant clinical studies evaluating the surgical treatment of macroglossia in patients with BWS, published in English, French, German or Dutch. Medline and Embase databases were systematically searched using relevant combinations of the following MESH headings and keywords: Beckwith–Wiedemann, macroglossia, surgery, tongue reduction, (partial) glossectomy. Small (single or double) case reports, letters, animal studies, and studies evaluating macroglossia lacking an association with BWS were excluded from the search. All relevant articles were used as additional sources of primary papers by crosschecking the reference sections with the master list of compiled articles. The crossreferencing process of locating other studies was continued until no further articles were generated. Results
From 1990 to 2010, 54 BWS patients presented at the authors’ craniofacial outpatient clinic with medical problems related to macroglossia. Conservative management
302
Kadouch et al. surgery after insufficient tissue removal at primary reduction. No recurrence of macroglossia was observed. Direct postoperative complications were seen in 2 cases (8%): one patient had postoperative airway obstruction after incorrect perioperative morphine administration (4%) and another suffered from partial wound dehiscence after 3 days (4%). No intubation problems were encountered. The average follow-up time was 7 years (range 1–19 years). Reported clinical outcome during follow-up demonstrated a satisfactory resting tongue position in all 23 surgically treated patients, defined as a tongue that lies within the alveolar ridge borders of the oral cavity for more than 95% of the time (Fig. 3). Persistent orofacial growth disturbance was present in one subject (4%) after 6 years. Speech problems were observed in one child (4%) with a general developmental delay caused by comorbidity. Complications of lingual nerve dysfunction were not observed in the study group. Literature study
Fig. 2. Anterior wedge resection technique as performed at the Academic Medical Center of Amsterdam. Illustrations by Serge A. Steenen.
of macroglossia was indicated in 31 patients with mild symptoms of macroglossia. Surgical treatment was indicated and performed in 23 patients with a yearly average varying from 0 to 3 subjects. In all cases, the senior author (C.M.A.M. vdH) performed the tongue reduction surgery using the anterior, V-shaped, wedge resection (AWR) technique. Patient demographics are shown in Table 1. There were 12 males and 11 females. Routine analysis of blood samples resulted in the following genetic subtype distribution: aberrant imprinting of Lit1 gene in 48%, aberrant imprinting of H19 gene in 13%, and UPD in 26%. In three subjects (13%), no molecular confirmation was found. Hemi-hypertrophic asymmetry of the tongue was observed in 30%, with the right greater than the left in 22% and the left greater than the right in 8% of the cases. Preoperative polysomnographic
investigation for suspected sleep-apnea related problems was performed in 5 patients (22%). In most cases (70%), the indication for tongue reduction surgery was based on a combination of significant tongue protrusion and other clinical problems related to the macroglossia such as feeding problems (39%), persistent drooling (35%), and swallowing difficulties (13%). Primary surgical indications, based on a solitary tongue protrusion (with subsequent anticipated problems in appearance), was reported in 7 cases (30%). All included patients underwent primary tongue surgery with a mean age of 19 months (range 3–68 months). Mean operation time was 29 min. Blood loss was not significant. Nine patients (39%) underwent other, additional procedures, including lingual frenulectomy in 5 patients (22%) and adenotonsillectomy in 4 patients (17%). One subject had secondary tongue
10 publications were identified18,19,22,25,27,33,34,37–39, describing 94 BWS subjects who underwent tongue reduction surgery. Here the authors review only the aspects of the papers that deal with the indications, the surgical techniques that were used for the correction of the macroglossia, and, if reported, the long-term outcome after surgery (Table 2). The number of patients who underwent tongue reduction surgery ranged from n = 322 to n = 17 patients39. The main indications prior to surgery were reported in only 7 studies, and varied from solitary tongue protrusion to multiple clinical problems such as drooling, speech developmental delay, and dental malocclusion18,19,22,27,33,34,37. The mean age at surgery ranged from 15 to 51 months. In the majority of the reported cases the AWR technique was performed for reduction of the tongue. Preoperative tracheostomies were reported in four cases19,33. Postoperative complications were mentioned in 4 of the 10 studies, and included wound dehiscence (n = 2)19, and recurrence of macroglossia (n = 4)18,19,22. Reports on clinical outcomes after tongue reduction surgery varied and were subjective. Discussion
In BWS, macroglossia is typically present at birth and may require surgical intervention in a small percentage of patients. To the best of the authors’ knowledge, this
Macroglossia in Beckwith-Wiedemann syndrome Table 1. Patient demographic and clinical data regarding tongue surgery at the Academic Medical Center of Amsterdam between 1990 and 2010. Characteristics
All patients n = 23
Gender Male/female Genetic subtype of BWS Aberrant imprinting Lit1 Aberrant imprinting H19 UPD No molecular confirmation Hemihypertrophy of tongue Right > left Left > right Preoperative polysomnographic registration Primary surgical indication Solitary tongue protrusion Combination of clinical problems Mean age at time of surgery (months) [range] Mean operation time (min) [range] Additional craniofacial interventions Frenuloplasty Adenotonsillectomy Jaw surgery Postoperative complications Airway obstruction Wound dehiscence Recurrence of macroglossia Mean follow-up time (years) [range] Reported clinical outcome Satisfactory resting tongue position Persistent oro-facial maldevelopment Speech problems
study is unique in describing the largest series of BWS patients that were surgically treated for macroglossia. 23 patients with BWS who underwent surgical tongue reduction at the authors’ institution are discussed. All procedures were performed by the same surgeon, using the same AWR technique. The literature pertinent to BWS and the surgical treatment of macroglossia revealed 10 other studies describing a total of 94 subjects. Previous reports regarding the treatment of macrolgossia in BWS have not yet included the underlying genetic component. When comparing the present results with the literature regarding BWS genotypes, a similar genetic subtype distribution is found in about 60% of patients with an aberrant imprinting in one of the imprinted clusters H19 or Lit1, about 20% of patients with a UPD, and about 15% of patients without molecular confirmation of the syndrome1. This may lead to the assumption that the differences in expression and severity of macroglossia are equally distributed over the genetic subgroups of BWS. Tongue function is important for deglutition, phonation, respiration, and to wet the lips. Also, tongue sensory function plays an essential role in the sense of taste. The clinical diagnosis of macroglossia is
n = 12/n = 11
% 100 52/48
n = 11 n=3 n=6 n=3 n=7 n=5 n=2 n=5
48 13 26 13 30 22 8 22
n=7 n = 16
30 70
19 months [3–68] 29 min [18–45] n=9 n=5 n=4 0 n=2 n=1 n=1 0 7 years [1–19] n = 23 n=1 n=1
39 22 17 0 8 4 4 0 100 4 4
made on the basis of subjective criteria by evaluating symptoms such as difficulties concerning respiration and protrusion of the tongue, drooling, phonation, and deglutition6,10. In the authors’ experience with BWS, the enlarged tongue varies in degree and severity. Hemi-hypertrophy was observed in 30% of the study patients. Unilateral enlargement of the tongue in BWS was only addressed in two other studies37,39. Of those, only the sample survey study performed by VAN BORSEL et al.39 noted 2 of their 40 respondents with a hemi-hypertrophic asymmetry of the tongue. In severe cases of macroglossia, the airway may be compromised at birth or later at rest, intermittently, related to position, or during feeding. Both KACKER et al. and RIMELL et al. described cases of severe airway obstruction due to macroglossia and the placement of a preoperative tracheostomy19,33. Acute airway obstruction due to macroglossia was not observed in any of the present patients, therefore no pre-tongue reduction tracheostomy was indicated. Sleep-apnea related problems were found in five of the present patients, who subsequently underwent polysomnographic evaluation. The outcome revealed a varying degree of upper airway resis-
303
tance syndrome in three of the five subjects, without any signs of classic obstructive sleep apnea syndrome. RIMELL et al. also observed milder signs of upper airway in seven of the nine patients who were followed up beyond 18 months of age. They concluded that obstruction in early infancy would be related to enlargement of the tongue base, and that airway obstruction occurring later in childhood most likely results from tonsil and adenoid hypertrophy33. When looking at the surgical indications, the present results were generally comparable with previous studies. Acute airway obstruction was not observed in the authors’ patients, but it was reported to be an important indication in subjects from three other studies18,19,33. Anticipated problem in appearance was a primary indication for tongue reduction surgery in 7 of the present subjects (30%), and played an important role in the indication of the other 17 patients operated on, as well as patients presented by six other studies18,19,27,33,34,37. In the majority of the authors’ cases (70%), the indication for tongue reduction surgery was based on a combination of significant tongue protrusion and functional deficits, such as difficulties in feeding, management of saliva (drooling) and swallowing, seen in 9, 8 and 3 patients, respectively. Similar indications were reported in only one other study performed by TOMLINSON et al.37. Particularly during feeding, the enlarged tongue overlying the teeth may result in repeated injuries of the tongue surface, causing bleeding and pain and eventually impairment of mastication32. Mandibular overgrowth served as an important surgical indication in at least 4 of the 10 other studies19,22,27,33 and was not seen as such in our patient group. This might be explained by the timing of tongue surgery. The aim of glossoplastic surgery is to reduce the size of the tongue, whilst maintaining normal tongue shape and function. A recent study performed by KAWAFUJI et al. demonstrates that untreated macroglossia may result in an anterior open bite and wide dental arch20. The present authors operated on subjects who presented with severe macroglossia with a minimum age of 3 months in an effort to reduce or prevent oro-facial growth disturbances. Late referral caused delayed surgical treatment in 4 cases. This resulted in a mean age at surgery of 19 months in this patient group, compared to a mean age of 29 months calculated from the selected literature review studies.
304
Kadouch et al.
Fig. 3. Facial appearances of BWS patients with macroglossia who underwent tongue reduction surgery at different ages (preoperative:at surgery:postoperative). Patient A, 0.2:0.3:0.4 year; Patient B, 0.6:0.9:1.7 year; Patient C, 0.8:0.9:5.1 years; Patient D, 4.9:5.7:6.5 years; Patient E, 4.3:4.5:7.5 years; Patient F, 0.2:0.8:12.3 years.
Knowledge of the anatomy of the tongue and the position of the lingual nerve is essential to allow safe performance of surgical tongue reduction for the treatment of macroglossia48. Whilst reducing the tongue, it is important to preserve the inferolateral neurovascular bundles and at the same time maintain the tongue shape2,15,23,31,48. Numerous surgical techniques have been developed for the treatment of macroglossia6,9,11,16,17,21,29,42. According to a recent study performed by HETTINGER et al., these procedures can be divided into 1 of 6 categories, including: tip amputations, AWR, central reductions (CR), dorsal flap excisions, marginal excisions (ME), and combination procedures (CP).
The results of the literature study demonstrate that the majority of procedures were performed by removal of tongue tissue in the midline via AWR or CR. Novel techniques also include submucosal removal of tongue tissue26, and tongue reduction using an ultrasonic aspirator49. Current experience with these two innovative methods is limited. In BWS, the tongue is enlarged in three dimensions and involves increased length, width and height of the muscle. Since the macroglossia is not phenotypically homogenous, surgical techniques designed for reducing tongue volume should be individually tailored for each patient19,37. The AWR procedure resulted in shortening of the tongue muscle in length and width (a
shortcoming of the AWR technique is that the tongue height remains unchanged). By varying the angle of the V-wedge, this procedure could be adjusted to both regular and more severe expressions of macroglossia. In case of tongue asymmetry, a larger portion could be excised from the hemihypertrophic side of the tongue. The authors’ mean operation time was 29 min and no problems were encountered during the surgical procedures. Despite the good vascularity of the tongue, blood loss was not significant and peri-operative hemostasis was achieved without difficulties. Postoperative management was mentioned in two studies. Both TOMLINSON et al. and KACKER et al. administered systemic steroids to avoid postoperative oedema of the tongue and monitored all patients in the ICU for possible airway obstruction19,37. The authors did not administer systemic steroids. Since substantial oedema was only located at the anterior tip of the tongue no postoperative airway obstruction was observed. As a consequence, the authors found no need for monitoring in the ICU and patients were directly admitted to the regular paediatric ward. Wound dehiscence, as seen in one of the present patients, was also reported by KACKER et al. and KVEIM et al.19,22. Recurrence of macroglossia as reported in the literature18,19,22, was not observed in the present study group. Multiple variables can affect the longterm outcome after partial glossectomy in a child with BWS. The timing of the intervention, the surgical technique, hearing and cognitive functioning are all known variables in the outcome after surgery of the tongue. In the present study, the reported clinical outcome during follow-up demonstrated a satisfactory resting tongue position in all 23 surgically treated patients after a mean follow-up of 7 years (range 1–19 years). Mandibular overgrowth (with subsequent Class III malocclusion) was present in one patient who was operated on at the age of 18 months, after follow-up of 6 years. In the literature selection, reports on clinical outcomes varied and were subjective. The study performed by TOMLINSON et al.37 was unique in describing long-term outcomes such as speech, tongue mobility, taste sensation and cosmesis after tongue reduction surgery in a detailed manner. They concluded that paediatric patients with BWS, who underwent glossoplastic surgery, are unlikely to have completely normal tongue function and appearance as adults. A small pilot study by MATSUNE et al. demonstrated that taste may decline after surgical reduction of the tongue,
Table 2. Existing data regarding surgical treatment and outcome of macroglossia in BWS. Age at surgery (months)
Surgical technique(s)
(1) Airway obstruction (2) Aesthetic appearance (3) Problems in speech
12–168 (mean 51)
CR (single or double stellate)
*Persistent macroglossia (n = 2)
No complaints of abnormal taste or sensation
Disproportionate tongue bulk (91%), abnormal tongue appearance (82%), specific speech sounds errors (73%), and short tongue tip (55%) Good speech and oral-motor outcome (70%)
Post-operative complications
Year
HETTINGER et al.18
2011
7
TOMLINSON et al.37
2007
11
(1) Tongue protrusion (2) Failure of oral competence (3) Persistent drooling
4–39 (mean 15)
AWR (sometimes with excised central tongue)
NM
SHIPSTER et al.34
2006
10
(1) Varying degrees of constant tongue protrusion
1–60 (mean 32)
AWR, CR (keyhole excision)
NM
MATSUNE et al.25
2005
4
NM
36–60 (mean 39)
AWR, CR
NM
Salty and bitter taste significantly declined in central tongue
KACKER et al.19
2000
4
(1) Airway obstruction (2) Varying degrees of tongue protrusion (3) Problems in speech (4) Cass III malocclusion
3–48 (mean 26)
CR (keyhole excision)
Tongue protrusion successfully treated in 3 out of 4 patients (75%)
VAN BORSEL et al.39
2000
17
NM
3–60 (mean 17)
AWR, CR, ME, CP
*Wound dehiscence (n = 2), *Persistent macroglossia (n = 1), *Preoperative tracheostomy (n = 2) None
RIMELL et al.33
1995
9
(1) (2) (3) (4) (5)
NM
AWR
Main indication(s)
Airway obstruction Aesthetic appearance Problems in speech Cass III malocclusion Dental caries
*Preoperative tracheostomy (n = 2)
Clinical outcome
Persistent articulation problems after tongue surgery (12%) Satisfactory resting tongue position in at least 3 operated subjects (33%)
Comments by author Retrospective chart review of 7 patients that underwent either a single stellate (n = 4) or a double stellate central (n = 3) tongue reduction Solitary detailed report on long-term outcome assessed by questionnaires (n = 11). Additional formal medical and speech pathology assessment in 4 patients Systematic investigation of oral motor skills and speech production preand post-tongue reductions surgery Study on taste after tongue reduction surgery, performed by impregnated filter papers compared to normal Japanese children Results of small series using keyhole technique
Sample survey study on relation between macroglossia and speech Airway obstruction during childhood might also be related to tonsillar and adenoid hypertrophy
Macroglossia in Beckwith-Wiedemann syndrome
Author
Operated subjects, N
305
Macroglossia should be treated symptomatically, no need for prophylactic resection
NM, not mentioned; AWR, anterior wedge resection; CR, central reduction; ME, marginal excision; CP, combination procedures.
NM AWR 3–36 (1) Varying degrees of tongue protrusion (2) Problems in speech (3) Cass III malocclusion MCMANAMNY et al.27
1985
16
AWR (1) Mandibular overgrowth (2) Cass III malocclusion KVEIM et al.22
1985
3
3–96 (mean 28)
*Wound dehiscence (n = 1) *Regrowth of the tongue (n = 1) NM
Persistent dental deformities (33%)
Reduction glossoplasty should be considered very early to prevent maxillofacial deformities and to ensure optimal cosmetic and functional outcome Prevention of dental deformity should assume greater priority Satisfactory results in both maxillofacial growth as well as cosmesis (100%) NM CR (single stellate excision) NM NM
Clinical outcome Year Author
13
Post-operative complications Surgical technique(s) Main indication(s)
Age at surgery (months) Operated subjects, N Table 2 (Continued )
1994
Comments by author
Kadouch et al.
VASQUEZ et al.38
306
they used impregnated filter papers with different flavours and compared operated BWS children to normal Japanese children25. In the present study group, no cases of lingual nerve dysfunction were observed during follow-up. It would be meaningful to investigate the taste in operated patients using a validated test. Speech improvement has also been reported as a result of tongue reduction24. Speech outcome after tongue surgery may affect sounds made primarily by the tip of the tongue against the upper or lower teeth or the anterior palate. In the study performed by VAN BORSEL et al., BWS patients with macroglossia were reported to have articulation problems, some of which persisted after corrective tongue surgery (mean age 1.4 years; range 3– 60 months) using different operative techniques39. Another retrospective study performed by SHIPSTER et al. found distinct speech errors caused by macroglossia that were subsequently eliminated by surgical tongue reduction using the anterior wedge resection or the ‘keyhole’ technique34. Speech problems were observed in one of the authors’ patients with a general developmental delay caused by comorbidity. No other specific speech problems were reported in the present patients; most probably as a result of early surgical intervention (the majority of patients underwent tongue surgery before the age of 2 years) and, if indicated, adjuvant speech therapy. The present results indicate that the AWR is a simple, effective and safe technique in the surgical treatment of paediatric BWS patients suffering from macroglossia. Primary limitations of this study include the retrospective nature of data collection. In order to evaluate the effects of tongue reduction properly, the authors will investigate tongue function, perform a speech assessment, and analyse oro-facial growth, in a multidisciplinary setting with objective and validated methods40. Detailed analyses in a greater number of subjects with BWS may help to evaluate the long-term impact of partial glossectomy further. Funding
None. Competing interests
None. Ethical approval
Not required.
Macroglossia in Beckwith-Wiedemann syndrome Acknowledgement. The authors would like
to thank S.A. Steenen for his illustrative support.
16. 17.
References 1. Bliek J, Maas SM, Ruijter JM, Hennekam RC, Alders M, Westerveld A, Mannens MM. Increased tumour risk for BWS patients correlates with aberrant H19 and not KCNQ1OT1 methylation: occurrence of KCNQ1OT1 hypomethylation in familial cases of BWS. Hum Mol Genet 2001;10:467–76. 2. Bracka A. The blood supply of dorsal tongue flaps. Br J Plast Surg 1981;34:379–84. 3. Chitayat D, Rothchild A, Ling E, Friedman JM, Couch RM, Yong SL, Baldwin VJ, Hall JG. Apparent postnatal onset of some manifestations of the WiedemannBeckwith syndrome. Am J Med Genet 1990;36:434–9. 4. Cohen Jr MM. Overgrowth syndromes: an update. Adv Pediatr 1999;46:441–91. 5. Cohen Jr MM. Beckwith–Wiedemann syndrome: historical, clinicopathological, and etiopathogenetic perspectives. Pediatr Dev Pathol 2005;8:287–304. 6. Davalbhakta A, Lamberty BG. Technique for uniform reduction of macroglossia. Br J Plast Surg 2000;53:294–7. 7. DeBaun MR, Tucker MA. Risk of cancer during the first four years of life in children from The Beckwith–Wiedemann Syndrome Registry. J Pediatr 1998;132:398– 400. 8. DeBaun MR, Siegel MJ, Choyke PL. Nephromegaly in infancy and early childhood: a risk factor for Wilms tumor in Beckwith–Wiedemann syndrome. J Pediatr 1998;132:401–4. 9. Dingman RO, Grabb WC. Lymphangioma of the tongue. Plast Reconstr Surg Transplant Bull 1961;27:214–23. 10. Dios PD, Posse JL, Sanroman JF, Garcia EV. Treatment of macroglossia in a child with Beckwith–Wiedemann syndrome. J Oral Maxillofac Surg 2000;58:1058–61. 11. Egyedi P. Reduction of tongue size in the surgical correction of jaw deformity. Br J Oral Surg 1965;3:13–21. 12. Elliott M, Bayly R, Cole T, Temple IK, Maher ER. Clinical features and natural history of Beckwith–Wiedemann syndrome: presentation of 74 new cases. Clin Genet 1994;46:168–74. 13. Engstrom W, Lindham S, Schofield P. Wiedemann-Beckwith syndrome. Eur J Pediatr 1988;147:450–7. 14. Filippi G, McKusick VA. The Beckwith– Wiedemann syndrome. Medicine (Baltimore) 1970;49:279–98. 15. Gasparini G, Saltarel A, Carboni A, Maggiulli F, Becelli R. Surgical management of macroglossia: discussion of 7 cases.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002;94:566–71. Gupta OP. Congenital macroglossia. Arch Otolaryngol 1971;93:378–83. Harada K, Enomoto S. A new method of tongue reduction for macroglossia. J Oral Maxillofac Surg 1995;53:91–2. Hettinger PC, Denny AD. Double stellate tongue reduction: a new method of treatment for macroglossia in patients with Beckwith– Wiedemann syndrome. Ann Plast Surg 2011;67:240–4. Kacker A, Honrado C, Martin D, Ward R. Tongue reduction in Beckwith–Wiedemann syndrome. Int J Pediatr Otorhinolaryngol 2000;53:1–7. Kawafuji A, Suda N, Ichikawa N, Kakara S, Suzuki T, Baba Y, Ogawa T, Tsuji M, Moriyama K. Systemic and maxillofacial characteristics of patients with Beckwith– Wiedemann syndrome not treated with glossectomy. Am J Orthod Dentofacial Orthop 2011;139:517–25. Kole H. Results, experience and problems in the surgical treatment of anomalies with reverse overbite. Int J Oral Surg 1965;19:427–50. Kveim M, Fisher JC, Jones KL, Gruer B. Early tongue resection for Beckwith–Wiedemann macroglossia. Ann Plast Surg 1985;14:142–4. Lauretano AM, Li KK, Caradonna DS, Khosta RK, Fried MP. Anatomic location of the tongue base neurovascular bundle. Laryngoscope 1997;107:1057–9. Massengill R, Pickrell K. Surgical correction of macroglossia. Pediatrics 1978; 61:485–8. Matsune K, Miyoshi K, Kosaki R, Ohashi H, Maeda T. Taste after reduction of the tongue in Beckwith–Wiedemann syndrome. Br J Oral Maxillofac Surg 2006;44:49–51. Maturo SC, Mair EA. Submucosal minimally invasive lingual excision: an effective, novel surgery for pediatric tongue base reduction. Ann Otol Rhinol Laryngol 2006;115:624–30. McManamny DS, Barnett JS. Macroglossia as a presentation of the Beckwith–Wiedemann syndrome. Plast Reconstr Surg 1985;75:170–6. Menard RM, Delaire J, Schendel SA. Treatment of the craniofacial complications of Beckwith–Wiedemann syndrome. Plast Reconstr Surg 1995;96:27–33. Mixter RC, Ewanowski SJ, Carson LV. Central tongue reduction for macroglossia. Plast Reconstr Surg 1993;91:1159–62. Moore ES, Ward RE, Escobar LF, Carlin ME. Heterogeneity in Wiedemann-Beckwith syndrome: anthropometric evidence. Am J Med Genet 2000;90:283–90. Morgan WE, Friedman EM, Duncan NO, Sulek M. Surgical management of macroglossia in children. Arch Otolaryngol Head Neck Surg 1996;122:326–9.
307
32. Perkins JA. Overview of macroglossia and its treatment. Curr Opin Otolaryngol Head Neck Surg 2009;17:460–5. 33. Rimell FL, Shapiro AM, Shoemaker DL, Kenna MA. Head and neck manifestations of Beckwith–Wiedemann syndrome. Otolaryngol Head Neck Surg 1995;113: 262–5. 34. Shipster C, Oliver B, Morgan A. Speech and oral motor skills in children with Beckwith Wiedemann Syndrome: pre- and post-tongue reduction surgery. Adv Speech Lang Pathol 2006;8:45–55. 35. Sotelo-Avila C, Gonzalez-Crussi F, Fowler JW. Complete and incomplete forms of Beckwith–Wiedemann syndrome: their oncogenic potential. J Pediatr 1980;96:47– 50. 36. Tan TY, Amor DJ. Tumour surveillance in Beckwith–Wiedemann syndrome and hemihyperplasia: a critical review of the evidence and suggested guidelines for local practice. J Paediatr Child Health 2006;42:486–90. 37. Tomlinson JK, Morse SA, Bernard SP, Greensmith AL, Meara JG. Long-term outcomes of surgical tongue reduction in Beckwith–Wiedemann syndrome. Plast Reconstr Surg 2007;119:992–1002. 38. Vasquez CV, Buis J, Schneid H, Martinez H, Le Bouc Y. Macroglossie congenitale et syndrome de Wiedemann-Beckwith. Ann Pediatr (Paris) 1994;41:303–15. 39. Van Borsel J, Van Snick K, Leroy J. Macroglossia and speech in Beckwith– Wiedemann syndrome: a sample survey study. Int J Lang Commun Disord 1999; 34:209–21. 40. van der Horst CM, Smeulders MJ, Polsbroek RM, Ravesloot JH. Development of a test for evaluation of taste perception after tongue reduction. J Craniomaxillofac Surg 2011; 38:452–4. 41. Vogel JE, Mulliken JB, Kaban LB. Macroglossia: a review of the condition and a new classification. Plast Reconstr Surg 1986;78:715–23. 42. Wang J, Goodger NM, Pogrel MA. The role of tongue reduction. Oral Surg Oral Med Pathol Oral Radiol Endod Oral 2003;95:269–73. 43. Weiss LS, White JA. Macroglossia: a review. J La State Med Soc 1990; 142:13–6. 44. Weksberg R, Nishikawa J, Caluseriu O, Fei YL, Shuman C, Wei C, Steele L, Cameron J, Smith A, Ambus I, Li M, Ray PN, Sadowski P, Squire J. Tumor development in the Beckwith–Wiedemann syndrome is associated with a variety of constitutional molecular 11p15 alterations including imprinting defects of KCNQ1OT1. Hum Mol Genet 2001;10:2989–3000. 45. Weksberg R, Shuman C, Smith AC. Beckwith–Wiedemann syndrome. Am J Med Genet C Semin Med Genet 2005;137C:12– 23.
308
Kadouch et al.
46. Weksberg R, Shuman C, Beckwith JB. Beckwith–Wiedemann syndrome. Eur J Hum Genet 2010;18:8–14. 47. Wiedemann HR. Frequency of WiedemannBeckwith syndrome in Germany; rate of hemihyperplasia and of tumours in affected children. Eur J Pediatr 1997;156:251. 48. Yang HM, Woo YJ, Won SY, Kim DH, Hu KS, Kim HJ. Course and distribution of the lingual nerve in the ventral tongue region:
anatomical considerations for frenectomy. J Craniofac Surg 2009;20:1359–63. 49. Yura S, Kato T, Ooi K, Izumiyama Y. Tongue reduction techniques with an ultrasonic surgical aspirator. J Oral Maxillofac Surg 2009;67:1568–71.
Address: Daniel J.M. Kadouch Department of Plastic
Reconstructive and Hand Surgery Academic Medical Center P.O. Box 22660 1100 DD Amsterdam The Netherlands Tel: +31 20 5662974; Fax: +31 20 6917549 E-mail: [email protected]