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 follow-up 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.
Beckwith–Wiedemann syndrome (BWS) is the most well-known paediatric overgrowth disorder and has an estimated incidence of 1 in 12,000 to 1 in 13,700 live births . The true birth prevalence is thought to be even higher due to milder, unrecognized clinical presentations . The clinical diagnosis of BWS is made using previously designed criteria . 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) .
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 pits .
Genetic analysis reveals an aberrant imprinting in either one or both imprinted clusters H19 or Lit1 in the majority of patients (80%) . 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) . 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 syndrome . The association between embryonic malignancies and BWS has been well documented, with most of the tumours occurring in the first 4 years of life .
Macroglossia is defined as a resting tongue that protrudes beyond the teeth or alveolar ridge . 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 ) .
Tongue reduction procedures are often performed in BWS patients when macroglossia causes one or more of the following problems : 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 been developed for the treatment of macroglossia . 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, peri-operative 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), oro-facial 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.
Regarding the surgical procedure, a V-shaped 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 cross-checking the reference sections with the master list of compiled articles. The cross-referencing 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 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 .
| Characteristics | All patients | % |
|---|---|---|
| n = 23 | 100 | |
| Gender | ||
| Male/female | n = 12/ n = 11 | 52/48 |
| Genetic subtype of BWS | ||
| Aberrant imprinting Lit1 | n = 11 | 48 |
| Aberrant imprinting H19 | n = 3 | 13 |
| UPD | n = 6 | 26 |
| No molecular confirmation | n = 3 | 13 |
| Hemihypertrophy of tongue | n = 7 | 30 |
| Right > left | n = 5 | 22 |
| Left > right | n = 2 | 8 |
| Preoperative polysomnographic registration | n = 5 | 22 |
| Primary surgical indication | ||
| Solitary tongue protrusion | n = 7 | 30 |
| Combination of clinical problems | n = 16 | 70 |
| Mean age at time of surgery (months) [range] | 19 months [3–68] | |
| Mean operation time (min) [range] | 29 min [18–45] | |
| Additional craniofacial interventions | n = 9 | 39 |
| Frenuloplasty | n = 5 | 22 |
| Adenotonsillectomy | n = 4 | 17 |
| Jaw surgery | 0 | 0 |
| Postoperative complications | n = 2 | 8 |
| Airway obstruction | n = 1 | 4 |
| Wound dehiscence | n = 1 | 4 |
| Recurrence of macroglossia | 0 | 0 |
| Mean follow-up time (years) [range] | 7 years [1–19] | |
| Reported clinical outcome | ||
| Satisfactory resting tongue position | n = 23 | 100 |
| Persistent oro-facial maldevelopment | n = 1 | 4 |
| Speech problems | n = 1 | 4 |
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 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 peri-operative 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 oro-facial 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
10 publications were identified , 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 ).
| Author | Year | Operated subjects, N | Main indication(s) | Age at surgery (months) | Surgical technique(s) | Post-operative complications | Clinical outcome | Comments by author |
|---|---|---|---|---|---|---|---|---|
| H ettinger et al. | 2011 | 7 | (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 | Retrospective chart review of 7 patients that underwent either a single stellate ( n = 4) or a double stellate central ( n = 3) tongue reduction |
| T omlinson et al. | 2007 | 11 | (1) Tongue protrusion (2) Failure of oral competence (3) Persistent drooling |
4–39 (mean 15) | AWR (sometimes with excised central tongue) | NM | Disproportionate tongue bulk (91%), abnormal tongue appearance (82%), specific speech sounds errors (73%), and short tongue tip (55%) | Solitary detailed report on long-term outcome assessed by questionnaires ( n = 11). Additional formal medical and speech pathology assessment in 4 patients |
| S hipster et al. | 2006 | 10 | (1) Varying degrees of constant tongue protrusion | 1–60 (mean 32) | AWR, CR (keyhole excision) | NM | Good speech and oral-motor outcome (70%) | Systematic investigation of oral motor skills and speech production pre- and post-tongue reductions surgery |
| M atsune et al. | 2005 | 4 | NM | 36–60 (mean 39) | AWR, CR | NM | Salty and bitter taste significantly declined in central tongue | Study on taste after tongue reduction surgery, performed by impregnated filter papers compared to normal Japanese children |
| K acker et al. | 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) | *Wound dehiscence ( n = 2), *Persistent macroglossia ( n = 1), *Preoperative tracheostomy ( n = 2) |
Tongue protrusion successfully treated in 3 out of 4 patients (75%) | Results of small series using keyhole technique |
| V an B orsel et al. | 2000 | 17 | NM | 3–60 (mean 17) | AWR, CR, ME, CP | None | Persistent articulation problems after tongue surgery (12%) | Sample survey study on relation between macroglossia and speech |
| R imell et al. | 1995 | 9 | (1) Airway obstruction (2) Aesthetic appearance (3) Problems in speech (4) Cass III malocclusion (5) Dental caries |
NM | AWR | *Preoperative tracheostomy ( n = 2) | Satisfactory resting tongue position in at least 3 operated subjects (33%) | Airway obstruction during childhood might also be related to tonsillar and adenoid hypertrophy |
| V asquez et al. | 1994 | 13 | NM | NM | CR (single stellate excision) | NM | Satisfactory results in both maxillofacial growth as well as cosmesis (100%) | Reduction glossoplasty should be considered very early to prevent maxillofacial deformities and to ensure optimal cosmetic and functional outcome |
| K veim et al. | 1985 | 3 | (1) Mandibular overgrowth (2) Cass III malocclusion |
3–96 (mean 28) | AWR | *Wound dehiscence ( n = 1) *Regrowth of the tongue ( n = 1) |
Persistent dental deformities (33%) | Prevention of dental deformity should assume greater priority |
| M c M anamny et al. | 1985 | 16 | (1) Varying degrees of tongue protrusion (2) Problems in speech (3) Cass III malocclusion |
3–36 | AWR | NM | NM | Macroglossia should be treated symptomatically, no need for prophylactic resection |
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