Craniofacial characteristics in cri-du-chat syndrome

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Please check he accu acy o he a ilia ion(s) o each au ho and make changes as app op ia e. a Lec u e , Mas e ’s P og am in O hodon ics and Den o acial O hopedics, School o Den is y, Uni e si y o Se ille, Se ille, Spain b Clinical Assis an in O al Su ge y, Uni e si y o Se ille, Se ille, Spain c P o esso o O al Su ge y, Depa men o S oma ology, Uni e si y o Se ille, Se ille, Spain d P o esso o Special Ca e Pa ien s, Depa men o S oma ology, Uni e si y o Se ille, Se ille, Spain e P o esso o O hodon ics, Chai man o O hodon ics, Depa men o S oma ology, Uni e si y o Se ille, Se ille, Spain P o esso o O al Su ge y, Chai man o O al Su ge y, Depa men o S oma ology, Uni e si y o Se ille, Se ille, Spain AUTHOR QUERIES AUTHOR PLEASE ANSWER ALL QUERIES 1 C anio acial cha ac e is ics in c i-du-cha synd ome Rosa-Ma ía Yáñez-Vico, BDS, MSc, a Ángela Rod íguez-Caballe o, BDS, b Alejand o Iglesias-Lina es, DDS, MSc, a Noelia Gue a-López, BDS, b Daniel To es-Laga es, DDS, MSc, c Guille mo Machuca-Po illo, MD, d En ique Solano-Reina, MD, MSc, e and José-Luis Gu ié ez-Pé ez, MD, Se ille, Spain UNIVERSITY OF SEVLLE Objec i e. The pu pose o his s udy was o analyze c anio acial cha ac e is ics om la e al head p o ile adiog aphs o pa ien s wi h c i-du-cha (CdC) synd ome. S udy design. The c anio acial mo phology o 10 CdC pa ien s was e alua ed using s anda d cephalome ic me hods, measu ing 39 c anio acial a iables on cephalome ic x- ay images. Resul s. The p incipal cha ac e is ics we e skele al class II malocclusion, caused by mandibula e ogna hism, den al bip o usion, and a small uppe ai way. Addi ionally, 70% o pa ien s had a s eep pala al plane angle; he c anial base angle was la ened, also in 70% o pa ien s. Conclusions. Resul s indica ed ha he dele ion o 5p had an impac on he c anial base, maxilla, mandible, and uppe ai way, causing dis inc i e ea u es o become appa en h ough i egula g ow h. (O al Su g O al Med O al Pa hol O al Radiol Endod 2010;xx:xxx) The c i-du-cha (CdC) synd ome, i s desc ibed by Lejeune e al., 1 is cha ac e ized by pa ial dele ion o he sho a m o ch omosome 5. The size o he dele ion anges om he en i e sho a m o egion 5p15 and 3 (5 o 40 Mb) only. 2,3 I s equency is es ima ed o be be ween 1:15,000 4 and 1:50,000 5 o li e-bo n in an s, bu he p e alence ound by Niebuh 4 in 6000 indi id- uals wi h men al e a da ion was app oxima ely 1:350. Fu he mo e, Schinzel’s da a 6 sugges ha i is he mos common au osomal dele ion synd ome in humans. The synd ome is cha ac e ized by a high-pi ched mono- ch oma ic c y like he mewing o a dis essed ki en, p obably because o anomalies o he la ynx and epiglo is as well as neu ological, s uc u al, and unc ional al e - a ions. 4 Addi ional clinical ea u es a e se e e psychomo- o and men al e a da ion, g ow h delay, and hypo onia. 2,4 Al hough he cha ac e is ic c y is usually conside ed di- agnos ic o he synd ome, 2 he ca like c y has been ound wi hou he ypical dysmo phic and se e e de elopmen al ea u es o he synd ome in indi iduals wi h he limi ed 5p15.3 dele ion. 2,7 C anio acial abno mali ies include mi- c ocephaly, sligh hype elo ism, epican hal olds, down- slan ing palpeb al issu es, s abismus, mal o med ea s, and hypodon ia. 8,9 E en hough he clinical ea u es a e well known as he esul o desc ip ions by se e al au ho s, 2,7,10 li le is known abou c anio acial de elopmen . The e a e some s udies based on an h opome ic da a, such as skull size, inne can hal dis ance, and e ogna hia. 4,11,12 Mo e e- cen ly, Kjae and Niebuh 13 in es iga ed he c anial base o pa ien s wi h CdC synd ome using p o ile adiog aphs and ound ha he condi ion in ol ed a mal o ma ion o he c anial base. They poin ed ou ha his pa icula c anial base egion de elops a ound he no ocho d, a he loca ion whe e he hombencephalic-de i ed b ains em, pons, and ce ebellum de elop do sally and whe e he neu ons mig a e en ally o he la ynx. They sugges ed ha a c anial de elopmen al ield, o igina ing a he no o- cho d loca ion, is in ol ed in he mani es a ions o CdC synd ome. Cephalome ics in ol es he use o la e al head a- diog aphs o measu e he skull and acial bones wi h espec o speci ic e e ence poin s. I is use ul o e alua ing and quan i ying g ow h and de elopmen ea u es, such as he ela ionship be ween he jaws, and be ween he jaws and he c anial bones. The pu pose o This wo k was suppo ed by a g an o he Depa men o S oma ol- ogy (CTS-523), awa ded by he Resea ch Ins i u e o he Uni e si y o Se ille (Spain). a Lec u e , Mas e ’s P og am in O hodon ics and Den o acial O ho- pedics, School o Den is y, Uni e si y o Se ille, Se ille, Spain. b Clinical Assis an in O al Su ge y, Uni e si y o Se ille, Se ille, Spain. c P o esso o O al Su ge y, Depa men o S oma ology, Uni e si y o Se ille, Se ille, Spain. d P o esso o Special Ca e Pa ien s, Depa men o S oma ology, Uni e si y o Se ille, Se ille, Spain. e P o esso o O hodon ics, Chai man o O hodon ics, Depa men o S oma ology, Uni e si y o Se ille, Se ille, Spain. P o esso o O al Su ge y, Chai man o O al Su ge y, Depa men o S oma ology, Uni e si y o Se ille, Se ille, Spain. Recei ed o publica ion May 24, 2010; e u ned o e ision Jul 21, 2010; accep ed o publica ion Aug 20, 2010. 1079-2104/$ - see on ma e © 2010 Published by Mosby, Inc. doi:10.1016/j. ipleo.2010.08.021 e1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 his s udy was o analyze c anio acial cha ac e is ics on la e al head p o ile x- ays in pa ien s wi h CdC syn- d ome. MATERIAL AND METHODS Six een pa ien s om he Spanish C i-du-cha Asso- cia ion and diagnosed wi h CdC synd ome by hei espec i e e e ence hospi als belonging o he Public Heal h Se ice we e selec ed om among pa ien s who had unde gone some p ocedu e in he Depa men o O al and Maxillo acial Su ge y a he Facul y o Den- is y, Uni e si y o Se ille (Spain). Six o hese indi- iduals we e excluded because he images showed poo quali y and mo ion a i ac s; excluded subjec s we e hose wi h se e e men al e a da ion who we e unable o emain s ill du ing he x- ay exposu e. As a esul , 10 pa ien s—2 males and 8 emales wi h a mean age o 23.9 ⫾6.7 yea s—we e selec ed o he analysis. The p esen s udy was ca ied ou wi h he ull knowledge and w i en consen o each subjec and in acco dance wi h he e hical p inciples go e ning medical esea ch and human subjec s, as laid down in he Helsinki Dec- la a ion (2002 e sion, h p://www.wma.ne /e/policy/ b3.h m). The da a ha e been ea ed wi h absolu e con- iden iali y. Me hods o ga he ing and s o ing da a a e subjec o he Spanish O ganic Law go e ning pe sonal da a p o ec ion. The Expe imen al E hics Commi ee a he Uni e si y o Se ille independen ly app o ed he p ocedu e. All subjec s we e pho og aphed and examined in a- and ex ao ally o gene al medical and den al indings. The p o ocol included gene a ing la e al cephalome ic digi al x- ay images, a 70 kV, 12 mA, wi h an expo- su e ime o 0.80 seconds (Odon o ama PC, T ophy, Cedex, F ance). Speci ic so wa e (Nemo ec, Mad id, Spain) was used o he digi al images om which c anio acial and den al measu emen s we e aken. An- a omical landma k coo dina es we e de ined and sum- ma ized as shown in Table I. C anio acial bones and ela ionships we e measu ed a e being classi ied in o 4 g oups: ai way analysis, skele al p oblems, den al p oblems, and es he ic p oblems. This classi ica ion p o ides use ul in o ma ion o de e mining which, i any, de elopmen al ield is a ec ed in CdC synd ome. In each g oup, angula and linea measu emen s we e assessed and quan i ied o his pu pose, as shown in Table II. Measu emen s ob ained om subjec s wi h he CdC synd ome we e compa ed wi h s anda d measu e- men s p o ided by he speci ic so wa e we used, and s anda d de ia ions calcula ed on he basis o s anda d- ized age, sex, and ace no ms. Cephalome ic analysis me hods by S eine , 14,15 Ricke s, 16 Ja aback and Fiz- zel, 17 and McNama a 18 we e used o ob ain s anda d measu emen s. The measu emen s e e ed o p e i- ously co espond o he mos ep esen a i e and widely used me hods acco ding o o hodon ic and c anio acial esea che s. The co espondence be ween cephalome - ic analyses and measu emen s used a e also shown in Table II. In aobse e e o was calcula ed o he sample, which was wice es ed. I was calcula ed in he ollowing way: SE ⫽公(⌺d2/2n), whe e d is he di - e ence be ween he double measu emen s and n is he numbe o pai ed double measu emen s. I was e alu- a ed using he S uden es o pai ed samples, wi h absence o signi icance ega ded as indica i e o con- co dance be ween mean alues. The da a ob ained we e analyzed using SPSS 17.0 so wa e o Windows (LEAD Technologies, USA). RESULTS The accu acy o in aobse a ional e o was 0.41 mm o linea measu emen s and 0.63° o angle mea- su emen s. The e we e no s a is ically signi ican di - e ences be ween o iginal and epea measu emen s (P⬎.05). Ai way analysis emphasized he educed olume in he uppe espi a o y ac (Table III). The g ea majo - i y o he acial pa e n measu emen s included sha ed meso acial cha ac e is ics. Howe e , he e a e pa ame- e s ha demons a e an ob ious e ical componen in he g ow h o s udy subjec s, such as a dec eased uppe gonial angle and an inc eased lowe gonial angle. By con as , we also ound an inc eased an e io acial heigh ( he dis ance be ween he nasion and men on landma ks). In con as , s anda d measu emen s we e ound o lowe acial heigh (ans-xi-pm) and an e o- in e io acial heigh (Na-me) (Table III). An inclined pala al plane was ound o be a s anda d ea u e o he analyzed subjec s. S a is ical equencies o his a iable show ha only 30% o subjec s had s anda d measu emen s and 70% had a ma ked slope. These da a ep esen one o he mos cha ac e is ic ea u es o CdC synd ome (Table IV). Measu emen s o he an e io and pos e io c anial base showed ha bo h we e educed compa ed wi h es ablished age, sex, and acial no ms. Howe e , in 70% o cases, he c anial base angle (s-na-ba) was la ge (Table V) when compa ed wi h age- ela ed s anda ds o no mal indi iduals. 19-21 Sagi al skele al ea u es a e all consis en wi h skele al class II malocclusion caused by mandibula e ogna hism (Table III). Wi h ega d o den al cephalome ic da a, we ound den al bip o usion, p o uding lowe inciso s, and ou - wa d-p o uding uppe inciso s (Table III). The main es he ic p oblem obse able om he ceph- alome ic acing was he p esence o a sho uppe lip wi h a igh nasolabial angle. The lowe lip no mally p o uded (Table III). OOOOE e2 Yáñez-Vico e al. Mon h 2010 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 AQ: 1 T1 T2 AQ: 2 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 AQ: 3 T3 T4 T5 DISCUSSION C i-du-cha synd ome was i s desc ibed in 1963 by Lejeune e al., 1 who comp ehensi ely explained he common clinical mani es a ions. Since hen, he li e a- u e has e e ed o pa ien s wi h CdC as exp essing c anio acial ea u es ha include hype elo ism, an i- mongoloid obliqui y o he palpeb al issu es, and a moon ace. Radiological ea u es, such as mic oenceph- aly and aul y long bone de elopmen ha e also been desc ibed. Many au ho s ha e epo ed on he clinical and adiological indings associa ed wi h his syn- d ome 8,10,13,22-25 ; none, howe e ha e measu ed c anio acial ea u es in ol ing he maxilla y and man- dibula bones. In CdC synd ome, he mono onous, high-pi ched c y like a ca is p obably he mos cha ac e is ic and s ik- ing clinical ea u e. 26 This has also been ound in ce ain kinds o diso de s o neu ological diseases. 4 Mo phologic la yngeal al e a ions, such as a small loppy, cu ed epiglo is, 27 la yngeal hypoplasia, a na - ow, diamond-shaped o quad angula la ynx, o an abno mal ai space in he pos e io a ea du ing phona- ion, 28 ha e all been said o esul in his cha ac e is ic c y. Ai way analysis ound a na ow uppe ai way olume, con i med by compu ed omog aphy s udies. 22 Ne e heless, subsequen s udies es ablished ha such ana omical al e a ions we e no necessa ily p esen in e e y pa ien and he exis ence o some o he o ganic o unc ional ac o was no being conside ed. 4 Thus, he s a is ical equency o a ma kedly inclined pala al plane, ound in 70% o he subjec s, sugges s ha i is a cha ac e is ic ea u e and p obably in ol ed in he Table I. Ana omical landma ks used Poin De ini ion Sella (S) Poin ep esen ing he cen e o he pi ui a y ossa Nasion (Na) Mos an e io poin o he on onasal su u e on he midplane Basion (Ba) Mos pos e o-in e io poin o he cli us A icula e (A ) The in e sec ion be ween he ex e nal con ou o he c anial base and he do sal con ou o he condyla head o neck. Tangen -gonion ( go) The poin o in e sec ion be ween he base and he amus angen s h ough gna ion and a icula e Men on (Me) The lowes poin o he jaw a he le el o he midsagi al plane o he symphysis Condylion (Co) The uppe mos poin o he mandibula condyle A poin (A) The mos pos e io poin on he an e io con ou o he uppe al eola p ocess Gna ion (Gn) The mos in e io poin on he mandibula symphysis Pogonion (Pg) The mos an e io poin on he mandibula symphisis Apex supe ius (As) The apex o he oo o he mos p ominen maxilla y cen al inciso Inciso su pe ius (Is) The midpoin o he incisal edge o he mos p ominen maxilla y cen al inciso Inciso in e ius (Ii) The midpoin o he incisal edge o he mos p ominen mandibula cen al inciso Apex in e ius (Ai) The apex o he oo o he mos p ominen mandibula cen al inciso Psps poin (psp) The mos pos e io poin on he so pala e Ppws poin (ppws) Closes poin on he pos e io o pha yngeal wall o psp poin Pb poin (pb ) In e sec ion o he pos e io bo de o he ongue and he in e io bo de o he mandible Ppwi poin (ppwi) Closes poin on he pos e io o pha yngeal wall o pb poin Pm poin (pm) The poin whe e he cu a u e o he an e io bo de o he symphysis changes om conca e o con ex Xi poin (Xi) A poin loca ed a he cen e o he amus P e igomaxilla e (P ) The in e sec ion poin o he in e io bo de o he o amen o undum and he pos e io wall o he p e igomaxilla y issu e Gonion (Go) The lowes , mos pos e io poin on he gonial angle o he mandible Po ion (Po) The mos supe io poin on he adiolucency o he ex e nal and in e nal audigo y mea i. I is loca ed pos e io o he mandibula condyle and pos e io cli us. O bi ale (O ) The mos in e io poin on he lowe bo de o he bony o bi CF poin (CF) The in e sec ion poin o he FH plane (F ank o ho izon al plane: a line connec ing he Po and O poin s) and he PTV plane (P e ygoid e ical plane: a line pe pendicula o he FH plane ho ugh he PT poin ). An e io nasal spine (ANS) The apex o he an e io nasal spine Pos e io nasal spine (PNS) The mos pos e io poin on he bonu ha d pala e in he midsagi al plane S omion supe ius (S s) The lowes midline poin o he uppe lip B poin (B) The deepes poin on he con ou o he mandible So isue pogonion (Pg´) The mos p ominen poin on he so issue con ou o he chin in he midsagi al plane Lab ale supe ius (Ls) The poin deno ing he e million bo de o he uppe lip in he midsagi al plane Lab ale in e ius (Li) The poin deno ing he e million bo de o he lowe lip in he midsagi al plane Subnasale (Sn) The poin in he midsagi al plane whe e he base o he columella o he nose mee s he uppe lip Columela nasal medium (Nm) Geome ic cen e on columela o de subnasal poin o he ip o he nose Cen e o c anium (Ce) The in e sec ion poin o he Ba-Na plane and he acial axis plane Condyle (Dc) The poin in he cen e o he condyle neck along Ba-N plane OOOOE Volume xx, Numbe x Yáñez-Vico e al. e3 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150 151 152 153 154 155 156 157 158 159 160 161 162 163 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150 151 152 153 154 155 156 157 158 159 160 161 162 163