Microsoft Word - Kaufer Proof 4-8.docx   Vol  3,  No  1  (2015)   ISSN  2167-­‐8677  (online)   DOI  10.5195/d3000.2015.33           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.   Agenesis  of  all  third  molars  in  two  half  siblings   Jamie  A.  Kaufer1       1  University  of  Pittsburgh  School  of  Dental  Medicine,  Pittsburgh  PA,  USA     Abstract     Tooth  agenesis   is  one  of   the  most   common  dental   anomalies   and   is   influenced  by   factors  including  pa0ent  gene#cs.  Although  there  are  several  specific  genes  associated  with   certain  pa*erns  of  agenesis,  there  does  not  seem  to  be  a  gene4c  pa*ern  iden4fied  to  date   that   is   associated  with   isolated   complete   third  molar   agenesis.   This   report   presents   two   half-­‐siblings  who  both  express  complete  agenesis  of  third  molars  despite  the  fact  that  their   shared  parent  does  not  express   the   same  phenotype.   The   case  discussion   focuses  on  ad-­‐ dressing   the   poten-al   gene-c   possibili-es   including   autosomal   dominant   inheritance   and   variable   expressivity   of   a  muta!on.     There   remains   an   uncertainty   to   the   exact   gene   in-­‐ volved.  Poten+al  op+ons  include  WNT10A  and  PAX9.  The  affected  individuals  are  not  need-­‐ ing  extrac+ons  or  experiencing  complica+ons  due  to  the  presence  of  third  molars.    Howev-­‐ er,  the  concern  remains  that  there  is  the  poten.al  for  more  severe  expression  of  the  muta-­‐ !on  in  future  genera!ons.     Cita%on:  Kaufer   JA.   (2015)  Agenesis   of   all   third   molars   in   two   half   siblings.   Den$stry   3000.   1:a001  doi:10.5195/d3000.2015.33   Received:  April  4,  2015   Accepted:    April    8,  2015   Published:    April  24,  2015   Copyright:  ©2015  Kaufer  JA.  This  is  an  open  ac-­‐ cess  ar!cle   licensed  under  a  Crea!ve  Commons   A"ribu%on  Work  4.0  United  States  License.   Email:  akl33@pi(.edu   Introduction   The  agenesis  of  teeth  has  been  con-­‐ tinuously  reported  as  one  of  the   most  common  dental  abnormalities   in  humans.  The  classifications  of   missing  teeth  are  in  three  catego-­‐ ries:  hypodontia  is  defined  as  miss-­‐ ing  one  to  six  teeth,  oligodontia   meaning  missing  more  than  six   teeth,  and  anodontia  missing  all   teeth.  The  definitions  of  both  hypo-­‐ dontia  and  oligodontia,  however,   exclude  third  molars  (commonly   known  as  wisdom  teeth).  The  agen-­‐ esis  of  third  molars  is  a  very  com-­‐ mon,  if  not  the  most  common,  pat-­‐ tern  of  tooth  agenesis  [1].  Many   genes  have  been  associated  with   tooth  development  [2].  Certain   genes,  including  PAX9,  MSX1,  AXIN2,   EDA,  EDAR,  EDARADD,  and  WNT10A   have  been  associated  with  specific   patterns  of  tooth  loss.  However   most  instances  of  tooth  agenesis  are   not  associated  with  any  of  these   genes.  PAX9  has  been  associated   with  third  molar  agenesis,  but  no   coding  mutations  in  that  gene  have   been  identified  that  explain  isolated   third  molar  agenesis  [3].  This  report   describes  a  case  of  third  molar   agenesis  between  two  half-­‐siblings   followed  by  a  discussion  of  poten-­‐ tial  genetic  influence.     Case  Report   A  24-­‐year  old  Caucasian  female  re-­‐ ported  to  the  University  of  Pitts-­‐ burgh  School  of  Dental  Medicine  for   routine  care.  Upon  taking  radio-­‐ graphs,  it  was  observed  that  her   third  molars  were  not  present.  The   patient  reported  that  her  third  mo-­‐ lars  were  not  extracted  and  had   never  erupted.  When  asked  further,   the  patient  stated  that  her  half-­‐ brother,  15  years  old,  was  also   missing  all  of  his  third  molars,  and   that  all  parents  of  the  siblings  had  at   least  two  wisdom  teeth.  Regarding   the  pedigree  (Figure  1),  the  only   information  that  could  be  complet-­‐ ed  was  of  the  immediate  parents.   Individual  2.5,  the  mother  of  indi-­‐ vidual  3.4,  had  two  wisdom  teeth,   both  in  the  maxillary  arch  and  fully   erupted.  Individual  2.3,  the  mother   of  individual  3.3,  had  all  four  wis-­‐ dom  teeth  removed.  Individual  2.4,   the  father  of  both  individuals  3.3   and  3.4,  had  three  third  molars  re-­‐ moved.  No  known  genetic  testing   for  any  individuals  in  the  family  re-­‐ garding  tooth  agenesis  has  been   completed.    It  should  be  noted  that   individual  3.3  is  missing  his  maxil-­‐ lary  first  premolars  as  well,  but  the-­‐    Agenesis  of  all  third  molars  in  two  half  siblings   Vol  3,  No  1  (2015)        DOI  10.5195/d3000.2015.33    http://dentistry3000.pitt.edu   2   se  were  extracted  in  preparation  for   orthodontic  treatment.     Discussion     In  most  research  regarding   tooth  agenesis,  third  molars  are  of-­‐ ten  excluded  from  the  studies.  It  is   for  that  reason  that  it  is  difficult  to   discuss  the  exact  potential  genetic   cause  of  agenesis  of  third  molars.   For  this  particular  case,  there  seems   to  be  some  history  of  missing  third   molars  for  individual  3.4  in  both  of   her  parents.  However,  neither  par-­‐ ent  is  missing  all  four  of  their  third   molars.  Individual  3.3  has  only  one   parent,  individual  2.4,  who  is  miss-­‐ ing  any  third  molars.  However,  de-­‐ spite  the  difference  in  parental   presence  of  third  molars,  the  same   phenotype  resulted  in  individuals   3.3  and  3.4.     As  mentioned  previously,   individual  2.5  is  missing  both  third   molars  in  the  mandible,  which  sug-­‐ gests  a  particular  pattern  of  agene-­‐ sis  associated  with  a  genetic  influ-­‐ ence.  For  individual  3.4,  there  is  a   chance  that  given  one  parent  ex-­‐ presses  a  phenotype  of  partial   agenesis  that  her  phenotype  of   complete  agenesis  is  the  result  of  an   inherited  mutation  with  more  se-­‐ vere  expression.  As  for  individual   3.3,  there  could  be  a  chance  of  in-­‐ herited  mutation  from  individual   2.4  or  2.3,  or  a  spontaneous  muta-­‐ tion.     Considering  individuals  3.3   and  3.4  have  the  same  phenotype   and  only  one  shared  parent,  there  is   also  the  potential  that  there  may  be   a  pattern  of  inheritance  in  this  fami-­‐ ly.  There  is  a  good  chance  that  this   case  follows  an  autosomal  dominant   pattern  of  inheritance.  Using  the   pedigree  as  a  reference,  it  is  unlike-­‐ ly  that  whatever  genetic  mutation   took  place  is  x-­‐linked  because  there   is  not  a  preference  for  a  particular   biological  sex.  It  is  also  unlikely  that   this  mutation  followed  an  autoso-­‐ mal  recessive  pattern  of  inher-­‐ itance.  In  order  for  this  case  to  be   recessive,  multiple  people  in  the   family  would  be  carriers  of  the   gene,  which  would  be  very  unlikely.       There  is  also  the  question  of   which  genes  may  be  involved  in  the   agenesis  molars  in  this  case.   WNT10A  mutations  are  the  most   common  identifiable  cause  of  hypo-­‐ dontia.  PAX9,  a  homeo-­‐ box  gene  on  chromosome   14,  has  also  been  associ-­‐ ated  with  preferential   agenesis  of  the  molars   due  to  haploinsufficiency.   Haploinsufficiency  means   that  missing  one  copy  of   the  gene  decreased  the   amount  of  translated   protein,  therefore  in-­‐ creasing  the  chance  of   missing  teeth  [4].  Anoth-­‐ er  possibility  for  these   two  individuals  is  varia-­‐ ble  expressivity  of  the   mutation  as  it  is  passed   down  to  further  genera-­‐ tions,  increasing  the   number  of  teeth  missing.   However,  because  a  genetic  test  for   this  condition  is  yet  to  be  devel-­‐ oped,  none  of  these  options  can  be   confirmed  with  complete  certainty.       There  could  be  some  impli-­‐ cations  both  in  terms  of  dentistry   and  the  future  of  those  affected.   Agenesis  of  third  molars  could  be   beneficial  in  that  they  will  not  influ-­‐ ence  relapse  following  orthodontic   treatment,  or  put  the  patient  at  risk   of  impaction  and  need  for  oral  sur-­‐ gery.  There  may  not  be  any  disad-­‐ vantages  in  terms  of  dentistry,   however  if  these  genes  can  be   passed  on,  those  involved  may  have   some  considerations.  If  this  muta-­‐ tion  only  affects  the  third  molars,   there  would  be  little  to  worry  about   in  passing  down  the  mutation.   However,  if  this  mutation  has  the   potential  to  cause  other  teeth  to  be   missing,  it  may  be  important  for   those  affected  to  know.       Conclusion     These  two  individuals  ex-­‐ hibit  a  very  common  dental  abnor-­‐ mality  that  is  most  likely  caused  by   an  autosomal  dominant  mutation.   There  is  little  reason  to  be  con-­‐    Agenesis  of  all  third  molars  in  two  half  siblings   Vol  3,  No  1  (2015)        DOI  10.5195/d3000.2015.33    http://dentistry3000.pitt.edu   3   cerned  for  the  future  generations,   unless  there  is  also  an  association   with  impairment  of  overall  health.     References   1. Genetic  basis  of  dental   agenesis-­‐-­‐molecular  genet-­‐ ics  patterning  clinical  den-­‐ tistry.  Chhabra  N,  Goswami   M,  Chhabra  A.  Med  Oral   Patol  Oral  Cir  Bucal.  2014   Mar  1;19(2):e112-­‐9.  Re-­‐ view.  PMID:  24121910       2. The  genetic  basis  of  tooth   development  and  dental  de-­‐ fects.  Thesleff  I.  Am  J  Med   Genet  A.  2006  Dec   1;140(23):2530-­‐5.  Review.   PMID:  16838332     3. Association  between  poly-­‐ morphism  in  the  promoter   region  (G/C-­‐915)   of  PAX9  gene  and  third  mo-­‐ lar  agenesis.  Bianch  FJ,  de   Oliveira  TF,  Saito  CB,  Peres   RC,  Line  SR.  J  Appl  Oral  Sci.   2007  Oct;15(5):382-­‐6.   PMID:  19089165     4. Vieira,  Alexandre  R  (May   2012)  Genetics  of  Congeni-­‐ tal  Tooth  Agenesis.  eLS.  John   Wiley  &  Sons,   Ltd:Chichester.  DOI:   10.1002/9780470015902.a 0023576