a multidisciplinary approach to the treatment of oral ......turity and capillary malformation also...

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Beckwith1 and Wiedemann2 pro-vided the first reports of Beckwith-Wiedemann syndrome (BWS) in1963 and 1964, respectively. Beck-

with1 described three postmortem casesinvolving extreme cytomegaly of theadrenal fetal cortex, omphalocele, hyper-plasia of kidneys and pancreas, andLeydig cell hyperplasia. Wiedemann2 sub-sequently reported his findings in threebrothers with similar symptoms, as wellas umbilical hernia and macroglossia.

The prevalence of BWS is estimated to be one in 14,000 births. The use ofassisted reproduction techniques canincrease the chances of BWS by four orfive times, which means an approximateprevalence of one in 3,000 in assistedreproduction births.3-10

BWS is a congenital disorder thatinvolves a somatic overgrowth during thepatient’s first years of life. It occurs becauseof an alteration in the 11p15.5 imprintedgene cluster, with a particularly importantrole being played by the reduced expressionor inactivation of the maternally expressed

Dr. Abeleira is an assistant professor, Pediatric Dentistry Unit, School of Medicine and Dentistry, Santiago de Compostela University, Spain.Dr. Seoane-Romero is a clinical fellow, Special Needs Unit, School of Medicine and Dentistry, Santiago de Compostela University, Spain.Dr. Outumuro is a clinical fellow, Special Needs Unit, School of Medicine and Dentistry, Santiago de Compostela University, Spain.Dr. Caamaño is a clinical fellow, Special Needs Unit, School of Medicine and Dentistry, Santiago de Compostela University, Spain.Dr. Suárez is a professor, Orthodontic Unit, School of Medicine and Dentistry, Santiago de Compostela University, Spain.Dr. Tomás Carmona is a senior lecturer, Special Needs Unit, School of Medicine and Dentistry, Santiago de Compostela University, C./Entrerrios s/n, 15782Santiago de Compostela, Spain, e-mail “[email protected]”. Address reprint requests to Dr. Tomás Carmona.

A multidisciplinary approach to the treatment of oral manifestationsassociated with Beckwith-WiedemannsyndromeA long-term case report

Maria Teresa Abeleira, DDS, PhD; Juan Manuel Seoane-Romero, DDS; Mercedes Outumuro, DDS;Flor Caamaño, DDS; David Suárez, MD, DDS, PhD; Inmaculada Tomás Carmona, DDS, PhD

AB ST RACTBackground. Beckwith-Wiedemann syndrome (BWS) isa congenital disorder that involves a somatic overgrowthduring the patient’s first years of life. Exomphalos,macroglossia and gigantism are the main clinical symptoms.Case Description. The authors describe a 15-yearfollow-up in a patient with BWS. They focus on a multidisci-plinary approach to treating the patient’s oral manifesta-tions from age 9 months. The approach included an initialphysiotherapy treatment, a partial glossectomy, a firstphase of orthopedic treatment with a tongue crib and chincap, and a second phase of orthodontic treatment with anedgewise appliance.Clinical Implications. To obtain long-term positive andstable results, an appropriate treatment plan for patientswith BWS and dentoskeletal alterations, including macro -glossia, requires surgical tongue reduction when the patientis young, combined with physiotherapeutic phases andorthopedic and orthodontic treatment.Key Words. Beckwith-Wiedemann syndrome; macro -glossia; tongue reduction; physiotherapeutic treatment;orthopedic treatment.JADA 2011;142(12):1357-1364.

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growth suppressor cyclin-dependent kinaseinhibitor 1C and the increased expression of thepaternally expressed growth promoter insulinlikegrowth factor type 2. These alterations can resultfrom multiple genetic and epigenetic mecha-nisms, including paternal uniparental disomy ofchromosome 11p15.5.11,12 Genetic testing shouldbe conducted in the diagnosis of BWS wheneverpossible and should include karyotype analysis,DNA methylation and genomic analysis of chro-mosome 11p15.5.13

Several investigators have described findingsassociated clinically with BWS.3,11,14-17 The mostcommon extraoral clinical findings are unusualearlobe creases, omphalocele, umbilical hernia,somatic overgrowth during infancy, nephro -megaly, hepatosplenomegaly, hemihypertrophyand hypoglycemia. Adrenocortical cytomegaly,polyhydramnios, advanced skeletal age, prema-turity and capillary malformation also are fre-quent findings. In rare cases of BWS, patientsalso can have diastasis recti, clubfoot, nys-tagmus and strabismus, and low attention spanwith hyperactivity. Anatomical brain malforma-tions, convulsions, slight mental impairment,scoliosis, congenital cardiopathy and diabetesalso have occurred. A patient with BWS is moresusceptible to developing cancer than are peoplein the general population, particularly duringthe first decade of life (average age, 2 years).18

Between 7.5 and 10.0 percent of patients withBWS develop a malignancy.18,19 This risk in -creases if the patient has hemihypertrophy ornephromegaly.3 The tumors usually are embry-onic and sensitive to biochemical markers, ultra-sonography or both.3 In 95 percent of patientswith BWS, the tumor appears in the abdomen,and most commonly are hepatoblastoma andWilms tumor.13,20 Because clinical findings ofBWS are variable, there are no absolute criteriafor making a diagnosis, but several of the asso-ciated findings should be present to support thediagnosis.13 Choufani and colleagues13 recom-mended that all children with a confirmed diag-nosis of BWS or who are suspected of havingBWS undergo an α-fetoprotein assay every threemonths to the age of 4 years and tumor surveil-lance, including abdominal ultrasonography,every three months to the age of 8 years, regard-less of the molecular etiology.

The infant mortality rate associated withBWS is approximately 21 percent; congestiveheart failure or severe malformations are themost common causes.21 However, once the infanthas survived any possible postpartum adaptivedifficulties, the prognosis usually is good, al -though the increased tumor risk in patients

with BWS has to be considered.22

The typical intraoral finding associated withBWS is macroglossia, which is a major criterionin diagnosing BWS.10,22 BWS occasionally hasbeen referred to as “EMG syndrome” because itsthree main clinical symptoms are exomphalos,macroglossia and gigantism.3,14,23 The occurrenceof hypotonia, including in the orofacial muscles,followed by early tooth eruption and cleft palate,also is a frequent clinical characteristic of BWS.3Investigators in previous articles have explainedthat early diagnosis and treatment of oral mani-festations of BWS can reduce the development ofdentoskeletal alterations and lead to a betterquality of life for patients with BWS.24,25

In this article, we report a case involving the15-year follow-up of a patient with BWS. Wefocus on the multidisciplinary approach we usedto treat oral manifestations in the patient.Treatments included physiotherapy, surgicalintervention, and orthopedic and orthodontictreatment.

CASE REPORTDuring the physical examination at birth, physi-cians observed macrostomia, muscular hypo-tonia, omphalocele, bilateral cryptorchism,alterations of both earlobes and macroglossia ina boy born in the 37th week of gestation to a 25-year-old primiparous woman who did nothave any relevant personal or family history. At9 months of age, the boy was admitted to theSchool of Dentistry at the University of San-tiago de Compostela, Spain, to be evaluated fororal health status. The most significant findingsof the complementary tests (blood test, chestradiograph, chromosomal study) that were con-ducted at the dental school when the boy was 9months old were hypoglycemia, which wentaway in 23 hours; symmetric myocardial hyper-trophy; and a normal karyotype. We diagnosedthe patient’s BWS.

During our oral examination of the patient,we observed hypotony of the perioral muscles, aprominent tongue that hung over the lower lip(true macroglossia) and severe drooling. Despitethe size of the patient’s tongue, he did not havesevere difficulty in sucking and swallowing.Therefore, we decided to have the patient startoral physiotherapy by using the Castillo-Morales technique, which is a method com-bining massage exercises for activation andstimulation and a palatal plate.26,27 We attacheda button to the posterior part of the plate so the


ABBREVIATION KEY. BWS: Beckwith-Wiedemannsyndrome.

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patient could stimulate his tongue, as well asground in channels so the patient could stimu-late his lip muscles. We also included a rotatingpearl on the posterior edge to enhance stimula-tion to a greater degree (Figure 1A).28 Takinginto account that the plate uses the gum profileand tongue to keep the plate in the correct posi-tion, we used dental floss to tie the plate to thepatient’s shirt to prevent aspiration of theplate.17,26,27 Once we placed the plate on thepalate, the patient had an immediate reaction(Weiffenbach reflex) because of the introductionof a foreign body in the mouth. When the tonguepresses on the palatal cylinder, it generates abackward and upward force that counteractsthe forward and downward position caused bythe muscular hypotonia, which keeps the tonguein the oral cavity. The boy’s parents placed theplate in position twice each day, starting for fiveminutes and then increasing the time progres-sively until it was 15 minutes per session.

After one month of treatment, we observedthat the patient drooled substantially less. Thepatient underwent physiotherapy and used theplate until he was aged 3 years. We replaced theplate three times between eruption of the ante-rior and posterior primary teeth (approximatelyevery nine-10 months), according to his maxil-lary growth and dental eruption.

At this time, the resting position and functionof the tongue had improved, although thepatient still had some difficulty in swallowing(Figure 1B). When he was age 4 years, wedecided to perform a partial glossectomy byusing the Egyedi and Obwegeser28 technique(Figures 1C and 1D), because he had developeda progressive anterior open bite secondary to aprolapsed tongue. The results of an oral func-tion evaluation we performed four months latershowed that surgical reduction of the tongue’svolume had improved the patient’s swallowingand made speech more intelligible. We recom-mended that the patient do stimulation exer-cises while his parents observed him. He was tocontinue these exercises at home until his per-manent first molars had erupted completely.

When the patient was aged 7.5 years, wedecided to start the first phase of orthopedic andorthodontic treatment. At that time, the patienthad a severe vertical mandibular growth withan anterior open bite, a skeletal Class III maloc-clusion apical base relationship with a normal-sized maxilla and a long mandible, and a Class Imalocclusion molar relationship with a slighttendency to transverse discrepancy and retarda-tion of permanent incisor eruption (Figure 2).Our objectives in this treatment phase were


Figure 1. Oral physiotherapy and surgical procedure per-formed in a patient with Beckwith-Wiedemann syndrome.A. Oral stimulation plate. B. Patient’s preoperative appear-ance after three years of physiotherapeutic treatment. C. The patient’s tongue immediately before undergoingglossectomy. D. The patient’s tongue immediately afterundergoing glossectomy.

A

C

D

B




inhibition of tongue protrusion, expansion of themaxillary dental arch and control of mandibularvertical growth.

First, the patient used consecutive maxillaryactive plates with a tongue crib and a plasticstimulating ball for about two years. The pa tientused two removable plates during this period,approximately one per year, to adapt the appli-ance to his maxillary growth changes and toimprove plate retention.

When the patient’s maxillary and mandibularpermanent incisors had erupted, we expanded hismaxilla by means of a fixed appliance, instead ofremovable plates, owing to the patient’s poorcooperation with the previously used removableplates. The patient used a Haas appliance for fourmonths (Figure 3A).

To avoid transverse relapse when no otherintraoral devices were being used, we placed alow palatal bar on the maxillary permanentfirst molars as a temporary retainer with anacrylic central button for vertical control and aplastic ball for tongue control. The patient worea vertical chin cap 10 to 12 hours per day toredirect mandibular growth until we began thenext phase of the treatment (Figure 3B).

When the patient was aged 12.5 years, westarted the second phase of orthopedic andorthodontic treatment by having him wear anedgewise appliance with intermaxillary elasticbands to achieve good alignment and occlusionof permanent teeth (Figure 3C). We also con-tinued to manage the mandibular vertical con-trol by having the patient wear a vertical chincap seven to nine hours per day until the end ofthis phase (the period of main mandibulargrowth). When the patient was aged 15.5 years,we placed the retention appliances: fixed lingualretainers on the maxillary and mandibular den-tition and a Hawley retainer on the maxillarydental arch. We also performed an esthetic res-toration in the maxillary left lateral incisor tomake its shape equal to that of the contralateralincisor. This multidisciplinary approach allowedus to achieve an improvement to skeletal Class Imalocclusion in the maxillomandibular relation-ship, with a counterclockwise rotation of theocclusal plane. We also maintained molar ClassI malocclusion at the end of active treatment.Eight months after we placed the retentionappliances, the patient had an acceptable occlu-sion and facial profile. He did not need to under-go a second surgical intervention on the tongueor orthognathic treatment (Figure 4, page 1362).

We analyzed cephalometric superimpositionsacross eight years, from the beginning to theend of orthodontic treatment,29,30 and we


Figure 2. The patient’s appearance with Beckwith-Wiedemann syndrome at age 7.5 years, when we decided tostart the first phase of orthopedic and orthodontic treatment.A. Cephalogram showing the main dental and skeletal struc-tures (black lines) and the functional occlusal plane (red line)between the maxillary and mandibular posterior teeth. B. Thepatient’s facial profile. C. Photograph showing occlusion.

A

B

C




observed that the standard deviation change(1.5˚) in the facial axis was normal for thisperiod (Figure 5A), despite the vertical growthof all of the components of the patient’s cranio-facial complex. This finding suggests that thepatient’s mandibular vertical growth was con-trolled because an excessive clockwise growthdid not take place. Figures 5B, 5C and 5D showmaxillary and mandibular growth, as well asmaxillary and mandibular tooth changes, all inthe midsagittal plane. Vertical skeletal growthand its dentoalveolar compensations are visible,especially in the maxillary and mandibularanterior teeth.

DISCUSSIONResults of previous studies have shown thatmacroglossia can lead to three types of compli-cations: dentoskeletal problems, such as man-dibular prognathism with an increase in man-dibular length, anterior open bite, higher gonialangle and anterior facial height and excessiveproclination of the mandibular incisors31-33; func-tional deficits such as difficulty in swallowing,drooling, alterations in speech and obstructionof the upper airway15,34-38; and psychological con-sequences derived from the patient’s appear-ance.39,40 Taking into account these repercus-sions, several patients with BWS, including theone in our case report, were treated surgically,orthopedically, orthodontically or by means of acombination of all three approaches, dependingon the clinic and the age of the patient.3

A logical approach to preventing or correctingthe effects of macroglossia is performing tonguereduction surgery, preferably before problems inspeech development occur, but not before thepatient is aged at least 6 months.23 In lesssevere cases of BWS, however, Müssig andZschiesche25 recommended an earlier orthopedicand physiotherapeutic intervention, based onthe use of a pacifier and stimulation plates totry to obviate the need for surgery while pro-viding adequate results. In the case we pre-sented, early use of oral physiotherapy did notobviate the need for the patient to undergo apartial glossectomy.

There are several successful tongue reductiontechniques. The main philosophy of these tech-niques involves reducing the central tonguebulk and the tongue’s length, while avoidingdamaging the neurovascular bundles that runinferolaterally.40,41 Among the various patientsfor whom clinicians have used partial glossec-tomy to treat BWS, different tongue reductiontechniques have been used: the Beckermethod,16 the keyhole technique,41-44 a wedge-


Figure 3. Orthopedic and orthodontic treatments per-formed in a patient with Beckwith-Wiedemann syndrome. A. Haas appliance (first phase, orthopedic treatment). B. Ver-tical chin cap (first phase, orthopedic treatment). C. Edge-wise appliance (second phase, orthodontic treatment).

A

B

C





Figure 4. The patient’s appearance with Beckwith-Wiedemann syndrome at age 15.5 years. A. Cephalogramshowing the main dental and skeletal structures (black lines)and the final functional occlusal plane (red line) betweenthe maxillary and mandibular posterior teeth. B. Thepatient’s facial profile. C. Photograph showing occlusion.

A

B

CFigure 5. Cephalometric superimpositions in the midsagittalplane of the patient with Beckwith-Wiedemann syndrome.Black indicates the pretreatment position, and red indicatesthe posttreatment position. A. Chin positional changes in thefacial axis. B. Maxillary growth. C. Mandibular growth andmandibular tooth changes. D. Maxillary tooth changes.

C

D

B

A




shaped technique,40,45 the Butlin-Handley tech-nique,46 the rhomboid technique47 and the cen-tral W-shaped technique.48 The keyhole tech-nique has been used most frequently. Thetongue reduction technique we used wasdescribed originally by Egyedi and Obwegeser.28

This technique involved a block excision of themiddle and tip of the tongue for adequate widthand length reduction. The basic advantages ofthis technique are the uniform reduction of thetongue and the preservation of the neurovas-cular bundle and the papillae at the sides andthe base of the tongue.49,50 Several short-termcomplications arising from partial glossectomymay occur, regardless of the tongue reductiontechnique used. The most common complica-tions are decreased articulation, less intelligiblespeech42-45,48 or a permanently large tongue.41,51

The patient whose case we report experiencednone of these complications.

Among the cases we mentioned earlier, thoselimited to preoperative and surgical treatmenthad no long-term follow-up after the partial glos-sectomy.25,41,43-48 In only one case we mentionedpreviously, investigators reported a follow-upacross nine years after partial glossectomyinvolving the use of a keyhole technique.42 Theyfound that besides the already existent speechcomplications, some dentoalveolar problems—such as Class III malocclusion, anterior openbite, diastema and overangulation of the man-dibular incisors—occurred. The patient in ourcase had some of these dentoalveolar andskeletal problems.

It seems appropriate to combine the tonguereduction surgery with subsequent physiothera-peutic, orthopedic or orthodontic treatment,because if the treatment plan is limited only toglossectomy performed when the patient isyoung, the most probable result is the correctionor avoidance of anteroposterior problems suchas mandibular prognathism. Vertical problemssuch as increased gonial angle and open bite,however, might not be corrected.52

The patients with BWS in the reported caseswho received orthodontic treatment—particu-larly two phases of treatment—had better andmore stable final results for dental occlusionand oral function than did those who did notreceive orthodontic treatment. In the first phaseof the treatment plan, which usually involvesplacing active plates with a tongue guard andthe use of a vertical chin cap, the patients hadan improvement in mandibular protrusion andanterior open bite.14,16,24,39,52 In isolated patients,clinicians used three types of orthodontic treat-ment during the second phase of the treatment

plan.14,16,52 As an alternative to the use of multi-bracket fixed appliances, they used other treat-ments such as a gnathologic positioner14 or sta-bility oriented appliances such as a bite blockwith a Nance holding arch or lingual arch.52

Miyawaki and colleagues16 designed a treat-ment plan similar to ours that was based onearly orthodontic treatment with the use of atongue crib and a chin cap and a second phaseinvolving fixed orthodontic treatment. Theirimplementation of their treatment plan resultedin positive and stable results after a 12-yearfollow-up. In the case we report, after a 15-yearfollow-up (the longest, to our knowledge), ourtreatment plan of surgical, physiotherapeutic,orthopedic and orthodontic treatment effectivelyimproved an abnormal dentoskeletal pattern,did not relapse and did not have any unexpectedcomplications.

CONCLUSIONSTo obtain long-term positive and stable resultsin patients with BWS who have dentoskeletalalterations, including macroglossia, an appro-priate treatment plan should involve surgicaltongue reduction performed when the patient isyoung combined with different physiothera-peutic phases and orthopedic and orthodontictreatments. We recommend having a multidisci-plinary dental and medical team create the clin-ical guidelines for patients with BWS. Ortho-dontists, in particular, play an essential role, asthey can evaluate and manage maxillary andmandibular growth to help establish the finaldental occlusion and oral function. �

Disclosure. None of the authors reported any disclosures.

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a multidisciplinary approach to the treatment of oral ......turity and capillary malformation also...

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