Gastro-oesophageal reflux - an important causative factor of severe tooth wear in Prader-Willi syndrome?

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1 Saeves et al. Orphaet Joural of Rare Diseases (2018) 13:64 RESEARCH Gastro-oesophageal reflux - a importat causative factor of severe tooth wear i Prader-Willi sydrome? Roaug Saeves 1*, Fi Strøm 2, Leiv Sadvik 3 ad Hilde Nordgarde 1 Ope Access Abstract Backgroud: Prader-Willi sydrome (PWS) is the most commo geetic huma obesity sydrome ad is characterized by hypotoia, edocrie disturbaces, hyperphagia, obesity ad mild metal retardatio. Oral abormalities, such as decreased salivary flow rates ad extreme tooth wear, have also bee described. Studies have show a sigificat icrease i reflux symptoms i idividuals with obstuctive sleep apoea sydrome ad icreased BMI, both of which are typical fidigs i PWS. Gastro-oesophageal reflux disease (GORD) has bee idetified i some idividuals with PWS ad is a sigificat itrisic factor i detal tooth wear. The aim of this study was therefore to estimate the prevalece of GORD i adults ad childre ad to evaluate a possible correlatio betwee GORD ad tooth wear i adults with PWS. They were all registered at the TAKO-cetre. Results: Twety-ie idividuals, 17 adults with a mea age of 32.6 years (rage 18 48)ad12childrewithameaage of 8.8 years (rage 3 17), agreed to udergo 24-hour oesophageal ph moitorig, ad 90% of those erolled maaged to complete the examiatio. Four childre ad eleve adults were diagosed with pathological gastro-oesophageal reflux, which is defied as acid exposure (ph less tha 4) more tha 3.6 or 4.3 percet of the time, respectively. Maometry performed i the adult group showed a pathologically high lower oesophageal sphicter pressure i four of the five idividuals who had ormal oesophageal ph values (ph uder 4 less tha 4.3% of the time). The two groups (reflux ad o-reflux) were well balaced accordig to BMI, geotype, tooth gridig ad hyposalivatio. However, twice as may idividuals i the reflux group as i the o-reflux group reported high cosumptio of acidic foods ad driks. Icreased tooth wear was sigificatly correlated with GORD i the two groups (reflux =6 ad o-reflux =6). Coclusios: The prevalece of gastro-oesophageal reflux is high i idividuals with PWS. Tooth wear was strogly associated with GORD ad acidic driks, ad both may be importat aetiological factors uderlyig the extreme tooth wear i this group. Our data suggest a eed for routie screeig for GORD ad detal wear i youg idividuals with Prader-Willi sydrome. Keywords: GORD, tooth wear, Prader-Willi sydrome Backgroud Prader-Willi sydrome (PWS) is a disorder affectig multiple orga systems ad is the most commo geetic huma obesity sydrome. Epidemiological surveys estimate that its populatio prevalece reaches 1:52000 [1 3], ad the geder ratio is close to 1/1 [1, 4]. The geetic mechaisms resultig i PWS are complex. The majority of idividuals with PWS (70%) have a paterally derived * Correspodece: roaug.saeves@tako.o 1 TAKO-cetre, Loviseberg Diacoal Hospital, Pb 4970 Nydale, 0440 Oslo, Norway Full list of author iformatio is available at the ed of the article deletio of 15q11-13, while materal disomy 15 (UPD) occurs i 25% of idividuals with PWS, ad the remaiig 2 to 5% have impritig defects [5, 6]. The typical PWS deletio falls ito oe of two classes, type 1 or type 2, depedig o the size ad the chromosome breakpoit positio. Whe the geotype-pheotype relatioships become clearer, it may be cliically importat to subtype the deletio classes [7]. Cliical diagostic criteria have bee developed, but as cliically overlappig disorders exist, the diagosis must be cofirmed by geetic testig [8]. PWS has a characteristic pheotype that icludes severe eoatal hypotoia, early feedig problems, childhood The Author(s) Ope Access This article is distributed uder the terms of the Creative Commos Attributio 4.0 Iteratioal Licese ( which permits urestricted use, distributio, ad reproductio i ay medium, provided you give appropriate credit to the origial author(s) ad the source, provide a lik to the Creative Commos licese, ad idicate if chages were made. The Creative Commos Public Domai Dedicatio waiver ( applies to the data made available i this article, uless otherwise stated.

2 Saeves et al. Orphaet Joural of Rare Diseases (2018) 13:64 Page 2 of 7 oset hyperphagia, obesity, short stature associated with growth hormoe deficiecy, a high pai threshold ad itellectual disability [9 11]. The sydrome has traditioally bee described as havig two utritioal stages: poor feedig ad failure to thrive i ifacy followed by hyperphagia leadig to obesity i later childhood [11 13]. The aetiology of the switch from poor feedig to hyperphagia is thought to be associated with abormalities i the hypothalamic circuitry [12]. The obesity ca be cotrolled by strict dietary restrictios. Growth hormoe treatmet improves growth, physical pheotype ad body compositio [8]. The Necdi gee is importat for the differetiatio of cetral ad peripheral sesory euros ad is cogeitally abset i PWS [14]. A arrow forehead, almod-shaped eyes, dow-tured corers of the mouth ad a thi upper lip are characteristic facial features of PWS. Varyig degrees of oral motor dysfuctio are also commo i affected idividuals [15]. Thick, viscous saliva is a cosistet fidig i idividuals with PWS [16 19]. Decreased salivary flow rates ad icreased amouts of salivary ios ad proteis have also bee reported [16, 17, 20] as well as severe tooth wear [18, 21, 22]. Tooth wear may result from attritio, abrasio, erosio or a combiatio of these factors. Attritio refers to the loss of eamel ad deti caused by the actio of atagoistic teeth, while abrasio refers to the loss of tooth structure caused by other forms of physical wear due to mechaical processes ivolvig foreig substaces or objects. Erosio refers to chemical wear due to extrisic or itrisic acids [23, 24]. The microscopic structure of eamel ad deti has bee foud to be ormal i teeth from idividuals with PWS [25]. There are may causes of tooth wear, ad it thus may be difficult to idetify the aetiology i idividual cases. However, the patter of tooth wear i idividuals with PWS suggests that erosive tooth wear is a importat factor [22]. Gastro-oesophageal reflux disease (GORD) is a aspect of geeral health that may affect erosive tooth wear, ad it has bee described i oe case report [26]. GORD is a sigificat itrisic factor i erosive tooth wear [27 31]. Excessive daytime sleepiess, sleep apoea ad cetral obesity are commo i idividuals with PWS [32 34]. Studies have show a sigificat icrease i reflux symptoms i idividuals with cofirmed obstructive sleep apoea sydrome ad icreased BMI (Body Mass Idex) [35, 36]. Cetral adiposity may be the most importat risk factor for the developmet of reflux [37]. To our kowledge o studies of gastro-oesophageal reflux i PWS have bee published. Due to the extreme tooth wear i may idividuals with PWS, GORD may be a serious problem ad a causal factor i tooth wear for may idividuals i this group. The aim of this study was to explore the prevalece of pathological GORD i adults ad childre ad to evaluate a possible correlatio betwee GORD ad tooth wear i adults with Prader-Willi sydrome. The ull hypothesis was o differece i the prevalece of tooth wear betwee idividuals with ad without pathological gastro-oesophageal reflux. Methods This study was performed at the TAKO-cetre, a atioal resource cetre for oral health i rare medical coditios (frequecy fewer tha 1:10 000), Loviseberg Diacoal Hospital (LDH), Oslo, Norway. The study followed a observatioal cross-sectioal study desig. The study protocol was approved by the Regioal Committee for Medical Research Ethics ad iformed coset was obtaied from all participats. For juveile participats uder 18 years of age ad adult participats with guardias, iformed coset was also obtaied from a paret or guardia. Study participats Fifty idividuals, all of whom had bee icluded i previous studies idetifyig salivary flow ad tooth wear [19, 22], were ivited to participate i the preset study. They received writte iformatio, desiged for both childre ad adults, describig the study. Eightee adults respoded ad agreed to participate. Oe ma who iitially agreed to participate later chaged his mid. Five childre respoded ad agreed to participate. I additio, seve more childre were icluded. All had bee examied ad followed at the TAKO-cetre durig the past three years, ad the same data were available for them as for those icluded i previous studies. The fial study group comprised 17 adults (11F, 6M, mea age = 32.6 years; rage 18-48) ad 12 childre (6F, 6M, mea age = 8.8 years; rage 3-17). Twety-four-hour oesophageal ph moitorig Seve adults were subjected to maometry ad 24-hour oesophageal ph moitorig at Loviseberg Diacoal Hospital, ad six of them maaged to complete the examiatios, while te idividuals were evaluated at other local hospitals. Prior to ad after each examiatio, the ph electrodes were calibrated usig stadard methods. Oesophageal maometry was performed i order to defie the positio of the sesor, 5 cm above the lower oesophageal sphicter (LOS), ad the pressure of the LOS. Cotiuous ph recordig was performed for 24 hours, ad the total reflux time durig the day ad ight was registered. The limits for pathological gastro-oesophageal reflux with acid exposure were set to a ph uder 4 more tha 4.3% of the time for adults [38] ad 3.6% of the time for childre [39].

3 Saeves et al. Orphaet Joural of Rare Diseases (2018) 13:64 Page 3 of 7 Twelve childre were referred to their local hospital to evaluate the degree of GORD. Te of them uderwet 24-hour oesophageal ph moitorig coducted at seve differet hospitals throughout the coutry. Noe of the 29 participats had udergoe ay prior surgical treatmet for GORD (i.e., ope Nisse fudoplicatio), ad oe had bee treated with percutaeous edoscopic gastrostomy (PEG). Cliical assessmets Childre: BMI criteria for the age group 3-17 years of age (=12) were age- ad geder-adjusted by comparig their BMI with the age- ad geder-specific cut-off values provided by the Iteratioal Obesity Task Force (IOTF) [40]. Tooth wear was ot evaluated i the youger age group (3-17 years) because may had mixed detitio. We also lacked baselie data from seve participats. Adults: All adult study participats were examied oce by the same examier ad uderwet a aamestic iterview either durig the cosultatio or, if parets or guardia did ot atted the cosultatio, by telephoe with a paret or guardia. The iterview focused o oral ad geeral health ad utritio, as well as symptoms of sleep disorders ad gastric reflux. The frequecy of cosumptio of acidic food ad driks was categorized as follows: more tha oce daily, oce daily, several times per week, oce per week, or ever. Iformatio about tooth gridig was also obtaied. BMI was calculated o the basis of measured height ad weight. To defie the BMI categories (kg/m 2 ), the sample was divided ito four groups (uderweight (<19.9)), ormal weight ( ), overweight ( ) ad obese ( 30)). Detal impressios (Aroma Fie Plus Normal Set, Algiate, GC Corporatio, Tokyo, Japa) were collected for adult idividuals. Tooth wear was evaluated usig two idices, the Visual Erosio Detal Examiatio (VEDE) scorig system [41] ad a modified idividual tooth wear idex (I A )[42]. The VEDE-idex, a modificatio of the detal erosio idex proposed by Lussi [43], is a 6-poit scorig system that cotais a visual guide with cliical photographs: 0=o erosive wear; 1=loss of eamel surface characteristics; 2=loss of eamel surface cotour; 3=loss of detie from less tha oe-third of the surface; 4=loss of detie from more tha oe-third ad less tha twothirds of the surface; 5=loss of detie from more tha two-thirds of the surface. A idividual mea VEDE-score was calculated by summig up the surface score (labial/ palatial) evaluated by cliical examiatio ad o detal casts for each tooth from upper right caie to upper left caie divided by the umber of teeth preset. Tooth wear o the occludig surfaces was evaluated o detal casts ad itraoral photographs usig the I A idex. This idex recorded tooth wear o a 4-poit scale: 0=o or miimal wear; 1=wear of eamel dow to detie spots; 2=wear of the detie dow to oe-third of the crow height; 3=wear of the detie greater tha oethird of crow height. I this study, the presece of a detal prosthetic crow due to tooth wear (accordig to the detal records) also qualified as a score of 3. The idividual tooth wear idex (I A ) was calculated usig the followig formula: (10G 1 +30G G 3 )/(G 0 +G 1 +G 2 +G 3 ), where G 0,G 1,G 2 ad G 3 = umber of teeth with occlusal wear scores of 0, 1, 2 ad 3, respectively [42]. Tooth wear was first evaluated i all participats by four examiers i 2007/2008, ad the results from that evaluatio were origially described i a previous paper [22] ad serve as a baselie for this report. I 2016, tooth wear was evaluated by oe examier (RS). The scores by RS i 2007 were close to the mea of the four examiers. The differeces betwee the scores (I A ad VEDE) from 2007 ad 2016 were used i the data aalyses. Statistical aalysis Whe comparig tooth wear (I A - ad VEDE idex) betwee the two groups (the pathological gastrooesophageal reflux ad the o-pathological gastrooesophageal reflux groups) a idepedet-samples t- test was applied. This applicatio was based o the assumptio that these variables are ormally distributed. By usig the fidigs from a relevat simulatio study [44], we foud that this assumptio was adequately met for both variables. A sigificace level of 5% was used throughout this work. The statistical aalysis was carried out usig the statistical software program (SPSS ; v. 24.0, SPSS Ic., Chicago, III., USA). Results Aamestic ad medical iformatio about the study group (=29) is show i Table 1. Three adults i the preset study reported dysphagia ad regurgitatio. Four childre ad eleve adults were diagosed with pathological gastro-oesophageal reflux with acid exposure (ph less tha 4) more tha 3.6 ad 4.3 percet of the time, respectively (Table 2). Two childre did ot complete the 24-hour oesophageal ph moitorig, but medicatio was iitiated based o cliical sigs. The oesophageal positio of the ph sesor, 5 cm above the lower oesophageal sphicter (LOS), was moitored. A pathologically high lower oesophageal sphicter pressure was reported i three of five idividuals who had ormal oesophageal ph values (a ph uder 4 less tha 4.3% of the time). Data from the maometry ad 24-hour oesophageal ph moitorig as well as the BMI, geotype, tooth gridig, itake of acidic foods ad driks ad ustimulated

4 Saeves et al. Orphaet Joural of Rare Diseases (2018) 13:64 Page 4 of 7 Table 1 Characteristics of the study populatio = 29 Age 3-17 yr Age yr Total, (%) Sex Female (59 %) Male (41 %) Geetic mechaisms Del (66 %) UPD (35 %) Body mass idex (BMI) Uderweight (<19.9) (4 %) Normal weight ( ) (41 %) Overweight ( ) (21 %) Obese ( 30) (31 %) Sleep disorder Sorig (35 %) Elarged adeoids (31 %) Apoea /CPAP (31 %) Del15, deletio of the pateral chromosome 15q11-q13; UPD15, materal uiparetal disomy for chromosome 15; BMI was age- ad sex adjusted for idividuals 3-17 years accordig to the Iteratioal Obesity Task Force (IONT) stadards [40]. Sleep disorders were assessed by a ENT specialist whole saliva secretio for the 16 adults are preseted i Table 3. Oe adult failed to complete the 24-hour oesophageal ph moitorig. Three idividuals i the oreflux group were evaluated ad had bee diagosed with pathological reflux i 2007; they used reflux medicatio durig the whole tooth wear registratio period. The two groups (the reflux ad o-reflux groups) were well balaced with respect to the followig variables: BMI, geotype, tooth gridig ad hyposalivatio. However, twice as may idividuals i the reflux group as i the o-reflux group reported high levels of cosumptio of acidic foods ad driks. The mea age was 26.8 years i the reflux group ad 35.5 years i the o-reflux group. Icreases i tooth wear as the mea I A ad VEDE scores i the two groups (reflux =6 ad o-reflux =6) registered over a mea of 7.5 years (3-9,5) are preseted i Table 4. The icrease i tooth wear was sigificatly correlated with GORD. Four idividuals were excluded from the data aalysis, two due to pathologically high LOS Table 2 Gastro-oesophageal reflux i the study populatio =29 Age 3-17 yr Gastro-oesophageal reflux Age yr Total, (%) Pathological (52 %) No pathological (38 %) Reflux (cliical) 2 2 (7 %) N/a 1 1 (4 %) pressure (>90 mmhg) ad two because they had detal crows placed o all their teeth followig the first tooth wear registratio i Three idividuals were diagosed with GORD diagosis ad used proto pump ihibitors for the whole period of tooth wear registratio; these idividuals were placed i the o-reflux group. Discussio As far as we kow, this study is the first to ivestigate the prevalece of gastro-oesophageal reflux disease (GORD) usig 24-hour oesophageal ph moitorig ad to evaluate the associatio of GORD with tooth wear i a group of idividuals with Prader-Willi sydrome. Fiftytwo percet of the total study group (17 adults, 12 childre) ad 69 percet of the adults showed pathological gastro-oesophageal reflux. This study demostrated a statistically sigificat associatio betwee GORD ad tooth wear i the adult study group. The ull hypothesis was therefore rejected. The study group was small, ad a larger group would have thus stregtheed the results. However, PWS is a rare disorder, ad as may as 17 of 26 adults who participated i the previous study i 2007 respoded. Good cooperatio was ecessary to participate i the evaluatio of 24-hour oesophageal ph moitorig, ad whe ivited, several parets ad guardias reported that it would be too challegig to participate i this study. The participats came from all over Norway, ad for this reaso, the 24-hour oesophageal ph moitorig eeded to be completed at twelve differet hospitals. Possible differeces i the procedures may etail bias. Three idividuals i the o-reflux group were evaluated ad had bee diagosed with pathological reflux i 2007; they used reflux medicatio durig the whole tooth wear registratio period. Mior leakage to the oesophagus i this periode thus caot be excluded. The idividuals were referred for their evaluatio of their 24-hour oesophageal acid exposure, ad data o the maometry fidigs were ot always oted i the medical reports set to us. However, pathologically icreased lower oesophageal sphicter (LOS) pressure was reported i five of 16 idividuals. Data o LOS was missig i five idividuals, ad those data would have stregtheed the results. All study participats were examied oce by a sigle examier (RS) ad tooth wear was evaluated based o two idices usig detal casts. I the previous study, four calibrated ad blided examiers evaluated tooth wear, based o the VEDE- ad IA idices to couter potetial bias. It was ot possible to utilize four examiers durig the last examiatio. However, the pricipal examier (RS) was a average observer of the four, which idicates acceptable validity.

5 Saeves et al. Orphaet Joural of Rare Diseases (2018) 13:64 Page 5 of 7 Table 3 Twety-four-hour oesophageal acid exposure ad maometry fidigs i 16 adults Idividual Age (yr) Sex Geotype BMI Reflux % Pat >4,3% a LOS pressure (mmhg) b Relaxatio pressure (mmhg) c UHS ml/mi d Tooth gridig 1 38 F Del 24, Norm 0.17 o M Del 33,3 20 N/a N/a 0.09 yes F UPD 41,1 4,8 N/a N/a 0.05 o M Del 38,1 0, yes F Del 44,7 2,4 89 Norm 0.02 o F Del 37,6 2, Norm 0.33 o M Del 34,9 18 Norm Norm 0.09 o F Del 27,6 6,9 N/a N/a 0.04 yes M UPD 25,1 13,8 Norm Norm 0.05 yes F UPD 23,0 0,8 91 Norm 0.24 yes F Del 26,4 9,6 16 Norm 0.16 yes F Del 22,5 0,3 N/a N/a 0.06 o M Del 26,8 10,9 7.6 Norm 0.11 o F Del 31,0 27, yes M UPD yes F Del 24,4 6,7 N/a N/a 0.21 o 1 a Reflux (pathological > 4.3%) b Lower Oesophageal Sphicter pressure (ormal values: mmhg) c Relaxatio pressure (ormal value <15) d Ustimulated whole saliva (hyposalivatio 0.10mL/mi) e Acidic foods ad driks (sugared ad diet soft driks carboated/ot carboated) more tha oce daily Acidic foods ad driks e I this study, we were able to follow the developmet ad icrease i tooth wear for a mea of 7.5 years ( ) for all adult participats. Moderate tooth wear may progress as a part of ormal agig [45]. I the preset study, the mea age of the reflux group was 27 years, ad i the o-reflux group, it was 36 years. After adjustmets for age ad age-related physiological tooth wear, the differece i tooth wear betwee the two groups would have bee eve greater. Gastro-oesophageal reflux is a aspect of geeral health that ca affect erosive tooth wear [28 31]. Both the acid ad fat cotets of food are kow to trigger GORD. I the preset study, lookig primarily at erosive tooth wear, we focused i particular o the cotet of acid ad ot fat i the diet. Idividuals with PWS live o a strict diet ( kcal) ad eat regularely. Their diet is based o vegetables ad light products, ad the focus is o reducig the fat cotet of their food. We therefore, do ot thik that fat is a trigger for GORD i the participats. Focusig Table 4 Tooth wear i the adult study populatio preseted as mea I A ad mea VEDE Idices Pathological reflux =6 No-pathological reflux =6 p-value I A ± ± VEDE 0.65 ± ± Statistical sigificace (p<0.05) o the aetiology of tooth wear, all aspects of aetiology ad cosequeces were ot icluded i the study desig. Studies have show a sigificat icrease i GORD symptoms i idividuals with obstructive sleep apoea sydrome, as well as icreased BMI ad cetral adiposity [36, 37] all of which are frequet risk factors ad commo to PWS [32]. The typical symptoms of GORD are heartbur ad acid regurgitatio. More atypical GORD symptoms may iclude a chroic cough, hoarseess, sleep disturbaces ad chest pais [46]. The prevalece of GORD varies i differet parts of the world. The highest populatio prevalece has bee reported i Europe (12 24%) [47, 48]. I a recetly published Norwegia study [48], the prevalece of at least weekly GORD was foud to be 17.1%, ad that of severe GORD of 6.7% reported due to GORD symptoms. I our small group study, 11 of 16 (69%) adults uderwet GORD diagosis. Four out of five idividuals i the o-reflux group preseted with high lower oesophageal sphicter pressure >80 mmhg (ormal rage: mmhg). The high LOS pressure may explai the mior leakage of acid to the oesophagus i these idividuals. This coditio ca occur at ay age, from early childhood to the ith decade of life. The two participats who had LOS pressure of 90 ad 100 mmhg (o-reflux) had received detal crows o all their teeth due to extreme tooth wear after the first examiatio i For this reaso, GORD at a earlier age caot be excluded as a

6 Saeves et al. Orphaet Joural of Rare Diseases (2018) 13:64 Page 6 of 7 aetiological factor. Noe of the PWS study participats reported symptoms of reflux or heartbur i the aamestic iterview i The symptoms of GORD may have bee uderreported, possibly due to the high pai threshold of PWS, which could i tur lead to the decreased recogitio of ijury or illess [49]. Alteratively, idividuals with the disorder may regard their log-stadig reflux symptoms as ormal ad therefore ot oteworthy. After startig o proto pump ihibitor medicatio, some of the participats reported GORD symptoms if the medicatio for some reaso was stopped for a period. Three idividuals i the preset study reported dysphagia ad regurgitatio. This is i lie with the fidigs of a study from Rumiatio is characterized by repetitive regurgitatio of gastric cotets ito the oropharyx [50] ad was reported by Alexader [51] i 53 out of 313 (17%) assessed idividuals with PWS. No data have bee published o rumiatio i PWS sice Tooth wear may be caused by attritio, erosio, abrasio or a combiatio of these processes. I the preset study, two idices were used, oe to focus o erosive tooth wear (VEDE) ad oe desiged to measure abrasio or attritio o occludig surfaces (I A ). Extesive tooth wear i PWS has bee demostrated ad appears to be a sigificat problem [18, 22]. The multifactorial ature of tooth wear, iflueced by variables such as hyposalivatio, tooth gridig, ad itrisic (gastric) ad extrisic acids (most commoly dietary), makes it difficult to establish its aetiology. GORD is a sigificat itrisic factor i erosive tooth wear [29, 30] ad is cosistet with our obsevatio of a strog associatio betwee GORD ad tooth wear. The microscopic structure of eamel ad deti i teeth from idividuals withpwshasbeefoudtobeormal.theeamelsurface was geerally smooth without structure, but could i some aspects resemble the effects of a acidic aget [25]. Earlier studies foud that saliva protects the teeth agaist tooth wear [21, 52]. I our previous study, the low salivary flow rate did ot maitai a sigificat associatio with tooth wear ad is therefore possibly oly a mior cotributory factor i extreme tooth wear. I the preset study, hyposalivatio was well balaced i both the reflux ad o-reflux groups. Dietary acids are cosidered to be the most commo cause of erosive tooth wear by may researchers [30, 53, 54]. These results are i accordace with the fidigs of the preset study. Coclusio To our kowledge, this is the first study addressig GORD i Prader-Willi sydrome. The prevalece of GORD seems to be high ad to icrease with age i PWS. Tooth wear was strogly associated with GORD ad the itake of acidic driks, ad both may be importat aetiological factors for the extreme tooth wear observed i this group. It is importat to be aware that GORD may be a health challege i idividuals with PWS, ad more studies o this are clearly ecessary. Our data suggest a eed for routie screeig for GORD ad tooth wear i youg idividuals with Prader-Willi sydrome. Abbreviatios BMI: Body mass idex; GORD: Gastro-oesophageal reflux disease; I A : Idividual tooth wear idex; LOS: Lower oesophageal sphicter; PWS: Prader-Willi sydrome; VEDE: Visual erosio detal examiatio Ackowledgemets The authors thak the Norwegia Prader-Willi sydrome associatio as well as all participats ad their families. Availability of data ad materials The datasets used ad aalysed i this study are available from the correspodig author upo reasoable request. Authors cotributios RS developed the study desig ad established the primary aims i cooperatio with HN. RS ad FS were resposible for the data collectio ad aalyses. RS wrote the paper i cosultatio with the co-authors ad takes the resposibility for the cotet. LS supported RS with the statistical aalysis sectio i the paper. HN critically reviewed the paper ad approved the fial versio. All authors read ad approved the fial mauscript. Authors iformatio RS; DDS, PhD. FS; Cad Med, Specialist i Gastroeerology. LS; Professor, Biostatistics. HN; DDS, PhD. Head of the TAKO-cetre. Ethics approval ad coset to participate The study protocol was approved by the Regioal Committee for Medical Research Ethics, South-East Norway. Ref r; 2013/1021. Coset for publicatio Iformed coset was obtaied from all participats. Whe participats were uder 18 years of age or had a legal guardia, iformed coset was obtaied from the paret or guardia as appropriate. Competig iterests The authors declare that they have o competig iterests. Publisher s Note Spriger Nature remais eutral with regard to jurisdictioal claims i published maps ad istitutioal affiliatios. Author details 1 TAKO-cetre, Loviseberg Diacoal Hospital, Pb 4970 Nydale, 0440 Oslo, Norway. 2 Loviseberg Diacoal Hospital, Oslo, Norway. 3 Departmet of Biostatistics ad Epidemiology, Oslo Uiversity Hospital, Oslo, Norway. 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