Microsoft Word - 77 2017.docx   Vol  5,  No  1  (2017)   ISSN  2167-­‐8677  (online)   DOI  10.5195/d3000.2017.77         http://dentistry3000.pitt.edu     New  articles  in  this  journal  are  licensed  under  a  Creative  Commons  Attribution  4.0  United  States  License.     This  journal  is  published  by  the  University  Library  System,  University  of  Pittsburgh  as  part  of  its  D-­‐Scribe  Digital  Publishing  Program  and  is  cosponored   by  the  University  of  Pittsburgh  Press.     Class  III  malocclusion:  an  argument  for  early  orthodontic  treatment   Eric  Moe1      1University  of  Pi.sburgh,  School  of  Dental  Medicine Abstract   Class   III  malocclusion   is   a   complex  mul0factorial   condi#on  with  many   gene#c   and   environmental   influences.  Most   o!en  the  condi*on  is  inherited  in  a  Mendelian  autosomal  dominant  pa3ern.  Early  referral  and  treatment  can  lead  to   be#er   outcomes   in   orthodon#c   therapy.   The   subject   presented   for   an   early   orthodon#c   referral   at   age   5.5   and   showed  signs  of   future  Class   III  malocclusion.  A   rapid  maxillary  expander  was  given  as   interven$onal   treatment   for   one  year.  At  age  11.5  the  subject  was  treated  with  braces  for  2  years.  The  outcome  was  a  normal  Class  I  occlusion.   The  subject’s  mother  had  Class  III  malocclusion  but  was  not  evaluated  early  and  was  only  able  to  establish  an  edge-­‐to-­‐ edge  Class  III  malocclusion  as  the  best  treatment  outcome  without  orthognathic  surgery.  The  subject’s  grandmother   was  also  Class  III,  establishing  an  autosomal  dominance  pa6ern  of  inheritance  in  the  family.  This  case  demonstrates   the  importance  of  the  general  den1st  educa1ng  families  about  malocclusion  and  making  orthodon-c  referrals  as  early   as  possible  so  the  best  treatment  outcomes  can  be  reached  through  orthodon3c  therapy.     Cita%on:  Moe,  E.  (2017)  Class  III  malocclusion:   an  argument  for  early  orthodon0c  treatment.   Den$stry  3000.  1:a001   doi:10.5195/d3000.2017.77   Received:    May  22,  2017   Accepted:    May  26,  2017   Published:    June  19,  2017   Copyright:  ©2017  Moe,  E.  This  is  an  open  access   ar!cle   licensed   under   a   Crea!ve   Commons   A!ribu"on  Work  4.0  United  States  License.   Email:  edm27@pi).edu   Introduction   Malocclusion  is  the  wide-­‐ ranging  diagnosis  given  when  the   dentition  from  the  two  arches  oc-­‐ clude,  or  come  together,  abnor-­‐ mally.  The  effects  of  malocclusion   can  include  decreased  masticatory   function,  compromised  esthetics,   and  heightened  risk  of  dental   trauma  [1].  Depending  on  the  se-­‐ verity  of  the  malocclusion,  the   overall  effect  is  that  quality  of  life   can  be  compromised  [1].  One  of   the  most  common  classification   systems  of  malocclusion  is  Angle’s   classification  which  designates   malocclusion  into  three  catego-­‐ ries:  Class  I,  II,  and  III.  This  case   report  focuses  on  Class  III  maloc-­‐ clusion,  which  is  defined  as  the   mesiobuccal  cusp  of  the  maxillary   first  permanent  molar  occluding   distally  to  the  buccal  groove  of  the   mandibular  first  molar,  instead  of   aligning  with  it.  Class  III  malocclu-­‐ sion  can  result  in  anterior  cross-­‐ bite  and  negative  overjet  or  an   edge-­‐to-­‐edge  incisal  relationship.   It  is  estimated  that  up  to  4%  of   European-­‐Americans  and  23%  of   Eastern  Asians  are  affected  by   Class  III  malocclusion  [2].  The  con-­‐ dition  can  be  diagnosed  from  a   young  age  and  it  often  becomes   more  evident  with  age  and  is  one   of  the  main  reasons  for  orthodon-­‐ tic  treatment  or  orthognathic  sur-­‐ gery  [2].  A  better  understanding  of   the  genetic  and  environmental   etiology  of  this  condition  could   lead  to  earlier  and  more  effective   treatment  options  for  those  af-­‐ fected.   Class  III  malocclusion  is  a   diverse  and  complex  phenotype   that  can  have  several  etiologies.   The  Class  III  phenotype  is  often   described  as  mandibular  progna-­‐ thism,  maxillary  retrognathism,  or   a  combination  of  both.  One  study   analyzing  lateral  cephalometric   variables  further  described  the   Class  III  phenotype  into  five  clini-­‐ cally  meaningful  phenotypes  [3]:   combination  of  mild  maxillary  ret-­‐ rognathism  and  mandibular  prog-­‐ nathism  with  a  flat  mandibular   plane,  combination  of  mild  maxil-­‐ lary  retrognathism  and  mandibular   prognathism  with  a  normal  man-­‐ dibular  plane,  large  mandible  ex-­‐ pressed  vertically,  severe  mandib-­‐ ular  prognathism,  and  severe  max-­‐ illary  retrognathism  [3].  The  ability   to  classify  the  phenotypes  associ-­‐ ated  with  Class  III  malocclusion  is  a   good  step  towards  discovering  the   genetic  etiology  of  each  pheno-­‐ type  [3].  With  the  complexity  of   development  and  the  numerous   ways  Class  III  malocclusion  can  oc-­‐ cur,  it  is  reasonable  that  Class  III   malocclusion  is  considered  a  mul-­‐ tifactorial  condition  with  both  ge-­‐ netic  and  environmental  influ-­‐ ences.    Class  III  malocclusion:  an  argument  for  early  orthodon6c  treatment   Vol  5,  No  1  (2017)        DOI  10.5195/d3000.2017.77    http://dentistry3000.pitt.edu   The  etiology  of  Class  III   malocclusion  is  multifactorial  and   involves  different  genes  and  envi-­‐ ronmental  factors.  Different   chromosomal  locations  and  genes   have  been  associated  with  Class  III   malocclusion  in  different  ethnic   populations  [2].  Family  studies  al-­‐ so  support  a  polygenic  multifacto-­‐ rial  inheritance  pattern,  as  13%  of   siblings  of  subjects  with  Class  III   malocclusion  also  exhibited  Class   III  malocclusion  [4].  Other  studies   analyzing  twins  have  found  that   the  rate  of  mandibular  progna-­‐ thism  in  monozygotic  twins  is  six   times  higher  than  dizygotic  twins,   also  suggesting  polygenic  inher-­‐ itance  and  etiology  [4].  However,   pedigree  analysis  of  Class  III  mal-­‐ occlusion  in  families  has  followed   an  autosomal  dominant  Mendeli-­‐ an  pattern  of  inheritance  with  in-­‐ complete  penetrance  in  a  majority   of  analyses  [2].  The  conclusion  of   many  of  these  studies  is  that  Class   III  malocclusion  within  families  is   explained  by  some  dominant  gene   being  inherited  in  an  autosomal   dominant  pattern,  while  likely  be-­‐ ing  modified  by   other  genes  and   environmental   influences  [2].   Unfortu-­‐ nately,  while   Class  III  malocclu-­‐ sion  can  often  be   described  as  a   Mendelian  auto-­‐ somal  dominant   inherited  condi-­‐ tion,  studies  have   already  located   many  genes  and   chromosomal  regions  that  are  as-­‐ sociated  with  this  condition,  show-­‐ ing  that  its  genetic  etiology  is  still   very  complex  and  not  easily  de-­‐ fined  to  one  or  two  genes  and  not   every  case  analyzed  is  easily  gen-­‐ eralized  to  all  people  of  all  ethnici-­‐ ties  [2].  For  example,  analyses  of   Korean  and  Japanese  families   showed  mandibular  prognathism   is  associated  with  chromosome   regions  1p36,  6q25,  and  19q13.2   [5].  Colombian  families  have   shown  Class  III  malocclusion  is  as-­‐ sociated  with  regions  1p22.1,   3q26.2,  11q22,  12q13.13,  and   12q23  [6].  Analyses  of  Han  Chi-­‐ nese  people  showed  regions   14q24.3-­‐q31.2  influence  mandible   growth  [7].  An  Estonian  family  was   described  as  having  the  mutation   p.Ser182Phe  in  DUSP6  leading  to   Class  III  malocclusion  [2].  All  of   these  cases  show  how  Class  III  oc-­‐ clusion  has  a  complex  genetic  eti-­‐ ology  that  is  multifactorial  and   variable.  Furthermore,  there  are   environmental  factors  that  may   contribute  to  the  development  of   Class  III  malocclusion.  The  man-­‐ dibular  bone  is  developed  from   condylar  cartilage,  and  mechanical   loading  may  influence  the  re-­‐ sponse  of  the  condylar  cartilage,   leading  to  growth  of  the  mandible   through  various  growth  factors  or   signaling  molecules.  These  factors   include  Indian  Hedgehog  homolog,   parathyroid-­‐hormone  like  hor-­‐ mone,  insulin-­‐like  growth  factor-­‐1,   and  vascular  endothelial  growth   factor.  It  is  possible  that  genes   coding  for  these  factors  may  ex-­‐ press  the  factors  at  levels  that   have  interactions  with  certain  en-­‐ vironmental  forces  at  play  that   combine  to  predispose  the  devel-­‐ opment  of  a  Class  III  phenotype   [4].   In  summary,  there  is  much   more  that  needs  to  be  learned   about  the  etiology  of  Class  III  mal-­‐ occlusion,  but  current  knowledge   shows  there  are  many  genes  and   environmental  factors  that  can   lead  to  the  condition.  Interesting-­‐ ly,  while  it  has  such  a  complex   multifactorial  genetic  and  envi-­‐ ronmental  etiology,  it  more  often   than  not  follows  an  autosomal   dominant  Mendelian  inheritance   with  incomplete  penetrance  that   is  likely  influenced  by  other  genes   and  environmental  factors.   Because  of  the  complex   and  poorly-­‐understood  etiology  of   Class  III  malocclusion,  treatment   plans  focus  on  fixing  symptoms   instead  of  preventing  etiology  [1].   The  two  main  concepts  to  consid-­‐ er  for  a  treatment  plan  are  its  tim-­‐ ing  and  type  of  appliance  [8].  Of-­‐ ten,  early  treatment  can  help  pre-­‐ vent  the  need  for  future  orthog-­‐ nathic  surgery,  so  a  fixed  ortho-­‐ dontic  treatment,  like  braces,  is    Class  III  malocclusion:  an  argument  for  early  orthodon6c  treatment   Vol  5,  No  1  (2017)        DOI  10.5195/d3000.2017.77    http://dentistry3000.pitt.edu   sufficient  instead.  Currently,  there   is  lacking  evidence  to  support  the   long  term  benefits  of  early  treat-­‐ ment,  but  short  term  evidence   shows  both  skeletal  and  dental   beneficial  effects  of  early  treat-­‐ ment  in  Class  III  malocclusion  [8].   Case  Presentation   The  Angle’s  Class  III  maloc-­‐ clusion  subject  is  a  Caucasian  male   who  first  presented  for  orthodon-­‐ tic  evaluation  at  5.5  years  of  age.   The  subject  presented  with  a   probable  Class  III  growth  pattern   that  may  become  more  obvious  as   growth  continued.  He  had  a  com-­‐ plete  anterior  crossbite  and  nor-­‐ mal  amount  of  anterior  overbite.   He  had  moderate  maxillary  crowd-­‐ ing  and  adequate  mandibular  arch   length.  The  maxillary  arch  was   constricted.  The  profile  of  the  sub-­‐ ject  was  prognathic.  The  subject   received  early  interventional  or-­‐ thodontic  treatment  with  a  bond-­‐ ed  rapid  maxillary  expander  and   reverse  pull  headgear  at  night  to   protract  the  maxilla  for  one  year.   The  subject  was  reevaluat-­‐ ed  after  interventional  treatment.   He  still  showed  a  possible  Class  III   growth  pattern  that  may  become   more  obvious  as  growth  contin-­‐ ues.  However,  the  interventional   treatment  was  successful  because   the  subject  had  normal  overjet,   indicating  the  complete  anterior   crossbite  was  eliminated.  The  sub-­‐ ject  had  adequate  maxillary  and   mandibular  arch  length,  indicating   the  moderate  maxillary  crowding   was  relieved.  The  evaluation  indi-­‐ cated  that  comprehensive  ortho-­‐ dontic  treatment  would  be  need-­‐ ed  in  the  future  and  that  the  sub-­‐ ject  should  be  periodically  reeval-­‐ uated.   At  11.5  years  of  age  the   subject  was  evaluated  to  have  an   edge-­‐to-­‐edge  incisal  relationship.   His  mandibular  midline  was  also   shifted  1-­‐2mm  to  the  right.  The   maxillary  arch  was  constricted   again.  At  this  time,  the  subject  re-­‐ ceived  full  fixed  braces  treatment   to  correct  the  edge-­‐to-­‐edge  incisal   relationship  and  other  findings.   The  expected  treatment  duration   was  24-­‐30  months  and  the  ex-­‐ pected  outcome  was  a  Class  I   normal  occlusion.  After  24  months   of  treatment,  the  subject  finished   the  course  of  treatment  with  a   Class  I  normal  occlusion  at  13.5   years  of  age.  Figure  1  shows  be-­‐ fore  (age  11.5)  and  after  (age  13.5)   pictures  of  the  subject’s  dentition.   Family  history  was  gath-­‐ ered  about  the  subject  in  terms  of   Class  III  malocclusion.  The  pedi-­‐ gree  for  all  known  relatives’  occlu-­‐ sion  before  any  orthodontic   treatments  is  shown  in  Figure  2.   The  subject’s  mother  and  his   grandmother  on  his  mother’s  side   also  had  Class  III  malocclusion.  No   one  else  in  the  family,  including   his  sister,  father,  and  all  other  rel-­‐ atives  had  Class  III  malocclusion.   A  limited  dental  history   was  obtained  from  the  subject’s   mother  in  regards  to  her  Class  III   malocclusion.  The  mother  had  a   similar  Class  III  malocclusion  to  the   subject,  but  she  did  not  receive   any  orthodontic  evaluation  or  in-­‐ terventional  orthodontic  treat-­‐ ment  until  she  was  13  years  of   age.  Her  outlook  at  that  time  was   either  orthognathic  surgery  or  a   probable  best  case  scenario  of  an   edge-­‐to-­‐edge  incisal  relationship   after  braces  treatment.  She  opted   for  braces  and  the  result  was  the   predicted  edge-­‐to-­‐edge  incisal  re-­‐ lationship,  which  was  better  than   the  more  severe  Class  III  malocclu-­‐ sion  at  the  beginning  of  treat-­‐ ment.  No  detailed  history  about   the  grandmother’s  Class  III  maloc-­‐ clusion  or  treatment  could  be  ob-­‐ tained.    Class  III  malocclusion:  an  argument  for  early  orthodon6c  treatment   Vol  5,  No  1  (2017)        DOI  10.5195/d3000.2017.77    http://dentistry3000.pitt.edu   Discussion   This  case  presents  a  pedi-­‐ gree  with  a  Mendelian  inheritance   pattern  of  autosomal  dominance   as  the  subject,  his  mother,  and  his   grandmother  all  have  Class  III   malocclusion.  While  the  pedigree   available  is  a  small  sample  size,  in   each  case  of  inheritance,  50%  of   the  children  received  the  Class  III   malocclusion  phenotype,  which  is   to  be  expected  with  an  autosomal   dominant  inheritance  pattern.  This   type  of  inheritance  pattern   matches  what  the  literature  re-­‐ ports  for  Class  III  malocclusion  be-­‐ ing  multifactorial  in  nature,  but   often  inherited  in  an  autosomal   dominant  manner.  It  is  likely  that   if  the  subject  has  offspring,  they   will  each  have  a  50%  chance  of   developing  a  Class  III  malocclu-­‐ sion.     This  case  also  demon-­‐ strates  the  importance  of  general   dentists  educating  families  with   young  children  about  malocclusion   early  on  and  making  early  referrals   to  orthodontists  for  evaluation  so   early  interventional  treatment  can   be  provided,  if  needed.  The  sub-­‐ ject  of  this  case  received  an  early   referral  at  the  age  of  5.5  and  re-­‐ ceived  a  rapid  maxillary  expander   for  one  year  before  fixed  appli-­‐ ance  braces  at  11.5  years  of  age   for  2  years  of  treatment.  It  is  likely   that  a  normal  occlusion  was  possi-­‐ ble  due  to  the  interventional   treatment  received  at  a  young   age.  This  course  of  treatment  can   be  compared  to  the  subject’s   mother  who  did  not  receive  any   interventional  treatment  or  evalu-­‐ ation  at  an  early  age.  Her  best   non-­‐surgical  treatment  outcome   was  a  Class  III  edge-­‐to-­‐edge  incisal   relationship.  This  shows  that  den-­‐ tists  have  the  ethical  implication   to  be  knowledgeable  and  thor-­‐ ough  in  recognizing  early  maloc-­‐ clusion  and  making  referrals.  This   includes  the  ethical  necessity  of   educating  the  family  about  why   following  up  with  the  orthodontic   referral  is  important.  The  dentist  is   also  in  an  advantageous  position   to  start  educating  the  family  when   the  children  are  born  about  the   possibilities  of  their  child  requiring   orthodontic  treatment  in  the  fu-­‐ ture  so  they  can  begin  to  plan  for   this  treatment  as  early  as  possible.   The  knowledgeable  dentist  will  be   able  to  educate  families  with  par-­‐ ents  that  have  Class  III  malocclu-­‐ sion  that  it  is  likely  that  their  chil-­‐ dren  may  also  have  Class  III  mal-­‐ occlusion  that  requires  treatment.   It  is  also  thorough  to  inform  par-­‐ ents  that  had  normal  occlusion   that  malocclusion,  and  specifically   Class  III  malocclusion,  is  complex   and  can  be  sporadic  as  well,  so  the   parents  know  it  is  possible  that   orthodontic  therapy  may  be  re-­‐ quired  for  their  children  even  if   they  did  not  require  it  themselves.   Overall,  this  case  shows  that  early   patient  education  and  early  or-­‐ thodontic  referral  and  treatment   can  help  the  patient  achieve  the   best  possible  outcome,  in  this  case   a  normal  occlusion,  when  present-­‐ ing  with  Class  III  malocclusion.   Conclusion     Class  III  malocclusion  has   several  phenotype  subgroups  that   result  from  a  complex  multifacto-­‐ rial  etiology  with  many  genes  and   environmental  factors  influencing   its  development.  In  many  cases,   Class  III  malocclusion  is  inherited   in  a  Mendelian  autosomal  domi-­‐ nant  pattern. 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