Microsoft Word - 76 2017.docx


	
  

Vol	
  5,	
  No	
  1	
  (2017)	
  
ISSN	
  2167-­‐8677	
  (online)	
  

DOI	
  10.5195/d3000.2017.76	
  	
  

	
  

	
  

	
  

http://dentistry3000.pitt.edu	
  

	
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  articles	
  in	
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  Creative	
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  License.	
  

	
  
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  journal	
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  University	
  of	
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by	
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  University	
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  Press.	
  

	
  

Assessment	
  of	
  dentofacial	
  variations	
  in	
  monozygotic	
  twins	
  
Victor	
  Tu1	
  
	
  
	
  1University	
  of	
  Pi.sburgh,	
  School	
  of	
  Dental	
  Medicine

Abstract	
  

With	
  dentofacial	
   development	
  being	
  a	
  mul4factorial	
   process,	
  we	
   face	
   the	
  ques1on	
  of	
  whether	
   gene#c	
  or	
   environ-­‐
mental	
   factors	
  play	
  a	
   larger	
  role	
   in	
  specific	
  phenotypic	
   traits.	
  The	
  use	
  of	
   twin	
  studies	
  allows	
  one	
  to	
  employ	
  gene/c	
  
controls	
   to	
   the	
   study	
   such	
   that	
  one	
   can	
   focus	
   solely	
  on	
   traits	
   that	
  may	
  be	
  more	
  environmentally	
  determined.	
   This	
  
study	
  involves	
  retrospec0ve	
  as	
  well	
  as	
  current	
  analy0cal	
  measurements	
  between	
  a	
  set	
  of	
  monozygo0c	
  twins	
  to	
  assess	
  
gene$c	
  and	
  outside	
  influences	
  on	
  facial	
  and	
  intraoral	
  development.	
  While	
  similari$es	
  were	
  acknowledged,	
  we	
  found	
  
differences	
   in	
  measurements	
  of	
  the	
  facial	
  thirds,	
  the	
  congenital	
  presence	
  of	
  mandibular	
  third	
  molars,	
  and	
  the	
  pres-­‐
ence	
  of	
  mandibular	
  tori.	
  

Cita%on:	
  Tu,	
  V.	
  (2017)	
  Assessment	
  of	
  dentofacial	
  
varia%ons	
  in	
  monozygo%c	
  twins.	
  Den$stry	
  3000.	
  
1:a001	
  doi:10.5195/d3000.2017.76	
  
Received:	
  	
  May	
  22,	
  2017	
  
Accepted:	
  	
  May	
  26,	
  2017	
  
Published:	
  	
  June	
  16,	
  2017	
  
Copyright:	
  ©2017	
  Tu,	
  V.	
  This	
   is	
   an	
  open	
  access	
  
ar!cle	
   licensed	
   under	
   a	
   Crea!ve	
   Commons	
  
A!ribu%on	
  Work	
  4.0	
  United	
  States	
  License.	
  
Email:	
  vwt2@pi(.edu

	
  

Introduction	
  

Dentofacial	
  development	
  is	
  
a	
  multifactorial	
  phenomenon	
  that	
  
relies	
  on	
  the	
  interactions	
  between	
  
multiple	
  genes,	
  environmental	
  
contributions	
  and	
  epigenetic	
  fac-­‐
tors	
  that	
  all	
  come	
  together	
  like	
  
pieces	
  of	
  a	
  puzzle	
  to	
  yield	
  a	
  defini-­‐
tive	
  set	
  of	
  phenotypic	
  attributes.	
  
Much	
  of	
  the	
  studies	
  on	
  dentofacial	
  
characteristics	
  and	
  pathologies	
  
have	
  been	
  focused	
  on	
  the	
  contrib-­‐
uting	
  role	
  of	
  genetics	
  in	
  the	
  hopes	
  
of	
  being	
  able	
  to	
  utilize	
  it	
  as	
  a	
  tool	
  
in	
  diagnosis	
  and	
  treatment	
  plan-­‐
ning.	
  This	
  has	
  led	
  to	
  the	
  confirma-­‐
tion	
  that	
  genetic	
  inheritance	
  is	
  the	
  
controlling	
  factor	
  in	
  facial	
  for-­‐
mation	
  through	
  craniometrical	
  
and	
  cephalometric	
  studies	
  of	
  facial	
  
similarities.	
  Furthermore,	
  similari-­‐
ties	
  in	
  craniofacial	
  bones	
  and	
  pro-­‐
files	
  are	
  observed	
  when	
  cephalo-­‐
grams	
  of	
  siblings	
  are	
  superim-­‐
posed	
  on	
  that	
  of	
  their	
  parents	
  
[5,6].	
  However,	
  the	
  use	
  of	
  
monozygotic	
  twin	
  studies	
  has	
  also	
  
helped	
  to	
  elucidate	
  how	
  heredi-­‐

tary	
  and	
  environmental	
  factors	
  
mesh	
  with	
  one	
  another	
  to	
  create	
  
the	
  final	
  physical	
  result.	
  This	
  is	
  at-­‐
tributed	
  to	
  the	
  reasoning	
  that	
  any	
  
differences	
  observed	
  in	
  a	
  physical	
  
feature	
  between	
  monozygotic	
  
twins	
  that	
  are	
  genetically	
  identical	
  
implies	
  that	
  environmental	
  factors	
  
may	
  play	
  a	
  significant	
  role	
  in	
  that	
  
aspect	
  of	
  a	
  person	
  compared	
  to	
  
the	
  other	
  more	
  genetically	
  con-­‐
trolled	
  phenotypes.	
  Past	
  studies	
  
between	
  monozygotic	
  adult	
  twins	
  
have	
  uncovered	
  differences	
  in	
  
measurements	
  of	
  the	
  anterior	
  
cranial	
  base,	
  man-­‐
dibular	
  body	
  
length,	
  total	
  facial	
  
height,	
  and	
  lower	
  
facial	
  height	
  [1].	
  	
  

Further-­‐
more,	
  another	
  
study	
  on	
  dental	
  
arch	
  forms	
  and	
  size	
  
demonstrated	
  that	
  
the	
  effect	
  from	
  en-­‐
vironmental	
  factors	
  
were	
  more	
  at	
  play	
  

for	
  this	
  part	
  of	
  development	
  ra-­‐
ther	
  than	
  genetics	
  alone	
  [2].	
  An-­‐
other	
  study	
  on	
  dental	
  arch	
  forms	
  
and	
  the	
  structure	
  of	
  individual	
  
teeth	
  of	
  several	
  monozygotic	
  twin	
  
pairs	
  showed	
  that	
  twins	
  are	
  not	
  
necessarily	
  always	
  occlusally	
  iden-­‐
tical	
  [4].	
  	
  An	
  analysis	
  on	
  42	
  pairs	
  of	
  
twins	
  found	
  hereditary	
  factors	
  to	
  
be	
  responsible	
  for	
  only	
  40%	
  of	
  the	
  
total	
  skeletal	
  and	
  dental	
  features	
  
that	
  caused	
  malocclusion	
  with	
  the	
  
genetic	
  component	
  being	
  more	
  of	
  
a	
  determining	
  factor	
  for	
  skeletal	
  
features	
  than	
  dental	
  features	
  [3].	
  



Assessment	
  of	
  dentofacial	
  varia1ons	
  in	
  monozygo1c	
  twins	
  

Vol	
  5,	
  No	
  1	
  (2017)	
  	
  	
  	
  DOI	
  10.5195/d3000.2017.76	
  

	
  http://dentistry3000.pitt.edu	
  

However,	
  genes	
  that	
  regulate	
  faci-­‐
al	
  proportions	
  and	
  jaw	
  relation-­‐
ships	
  may	
  still	
  play	
  an	
  indirect	
  role	
  
in	
  determining	
  occlusion.	
  	
  

Regardless,	
  occlusal	
  rela-­‐
tions	
  seem	
  to	
  be	
  more	
  effected	
  by	
  
the	
  environment.	
  As	
  with	
  any	
  mul-­‐
tifactorial	
  process,	
  there	
  is	
  debate	
  
in	
  terms	
  of	
  whether	
  genetic	
  or	
  en-­‐
vironmental	
  factors	
  are	
  weighted	
  
more	
  in	
  terms	
  of	
  the	
  final	
  out-­‐
come.	
  Twin	
  studies	
  offer	
  the	
  
chance	
  to	
  gain	
  insight	
  into	
  wheth-­‐
er	
  there	
  are	
  other	
  factors	
  at	
  play	
  
in	
  terms	
  of	
  development	
  when	
  
genetic	
  factors	
  are	
  controlled	
  for.	
  	
  

Subjects	
  and	
  Methods	
  

This	
  study	
  involves	
  retro-­‐
spective	
  sources	
  and	
  current	
  facial	
  
measurements	
  to	
  gauge	
  differ-­‐
ences	
  in	
  dentofacial	
  development	
  
between	
  twin	
  A	
  and	
  twin	
  B.	
  In	
  ad-­‐
dition	
  to	
  past	
  photographs	
  (Figure	
  
1),	
  current	
  facial	
  measurements	
  
were	
  taken	
  to	
  help	
  assess	
  differ-­‐
ences	
  in	
  a	
  quantitative	
  way	
  (Table	
  
1).	
  While	
  most	
  of	
  the	
  measure-­‐
ments	
  were	
  self-­‐explanatory,	
  the	
  
first	
  facial	
  third	
  was	
  taken	
  as	
  the	
  
distance	
  between	
  the	
  trichion	
  and	
  
the	
  glabella.	
  The	
  middle	
  third	
  is	
  
the	
  distance	
  from	
  the	
  glabella	
  to	
  

the	
  subnasale.	
  Finally,	
  the	
  lower	
  
third	
  was	
  measured	
  from	
  the	
  sub-­‐
nasale	
  to	
  the	
  menton.	
  Twins	
  A	
  and	
  
B	
  are	
  currently	
  under	
  Invisalign	
  
treatment.	
  Patient	
  treatment	
  dia-­‐
grams	
  from	
  the	
  start	
  of	
  treatment	
  
are	
  shown	
  in	
  figure	
  2	
  to	
  provide	
  a	
  
snapshot	
  of	
  the	
  occlusion	
  before	
  
treatment.	
  Past	
  bitewing	
  radio-­‐
graphs	
  combined	
  with	
  current	
  in-­‐
traoral	
  pictures	
  were	
  taken	
  to	
  as-­‐
sess	
  the	
  oral	
  condition	
  (Figure	
  3).	
  

Results	
  and	
  Discussion	
  

Dentofacial	
  development	
  is	
  
a	
  multifactorial	
  process	
  but	
  it	
  is	
  
unknown	
  how	
  involved	
  environ-­‐
mental	
  factors	
  are	
  in	
  particular	
  

aspects	
  of	
  the	
  final	
  outcome.	
  As-­‐
sessing	
  the	
  photos	
  in	
  Figure	
  1,	
  one	
  
should	
  be	
  able	
  to	
  detect	
  subtle	
  
differences	
  already	
  between	
  twin	
  
A	
  and	
  twin	
  B	
  after	
  birth.	
  Over	
  time	
  

as	
  these	
  twins	
  mature	
  in	
  growth	
  
and	
  development,	
  these	
  differ-­‐
ences	
  are	
  magnified.	
  To	
  assess	
  
these	
  measurements	
  in	
  a	
  quanti-­‐
tative	
  fashion,	
  facial	
  measure-­‐
ments	
  were	
  taken	
  between	
  twin	
  A	
  
and	
  twin	
  B,	
  which	
  presents	
  largely	
  
a	
  general	
  consensus	
  in	
  facial	
  out-­‐
come.	
  Of	
  greatest	
  interest	
  is	
  the	
  
difference	
  in	
  measurement	
  in	
  the	
  
middle	
  and	
  lower	
  thirds	
  of	
  the	
  
face,	
  where	
  one	
  finds	
  the	
  greatest	
  
amount	
  of	
  dissimilarity.	
  One	
  plau-­‐
sible	
  explanation	
  is	
  based	
  on	
  the	
  
growth	
  pattern	
  of	
  the	
  lower	
  half	
  
of	
  the	
  face.	
  Lower	
  facial	
  develop-­‐
ment	
  occurs	
  at	
  relatively	
  fewer	
  
growth	
  sites	
  and	
  over	
  a	
  more	
  ex-­‐
tended	
  period	
  of	
  time	
  compared	
  
to	
  the	
  upper	
  half	
  of	
  the	
  face	
  [1].	
  
The	
  form	
  and	
  size	
  of	
  the	
  upper	
  
facial	
  region	
  is	
  dependent	
  on	
  nu-­‐
merous	
  elements	
  that	
  interact	
  in	
  a	
  
more	
  complex	
  set	
  of	
  pathways	
  [1].	
  
With	
  less	
  growth	
  sites	
  on	
  the	
  low-­‐
er	
  half	
  of	
  the	
  face,	
  one	
  can	
  ex-­‐
trapolate	
  that	
  genetic	
  factors	
  are	
  
less	
  involved	
  in	
  lower	
  facial	
  devel-­‐

opment,	
  which	
  opens	
  the	
  door	
  for	
  
environmental	
  factors	
  to	
  leave	
  a	
  
greater	
  impact	
  in	
  facial	
  develop-­‐
ment	
  of	
  the	
  lower	
  half.	
  	
  



Assessment	
  of	
  dentofacial	
  varia1ons	
  in	
  monozygo1c	
  twins	
  

Vol	
  5,	
  No	
  1	
  (2017)	
  	
  	
  	
  DOI	
  10.5195/d3000.2017.76	
  

	
  http://dentistry3000.pitt.edu	
  

Despite	
  the	
  fact	
  that	
  previ-­‐
ous	
  studies	
  have	
  found	
  that	
  envi-­‐
ronment	
  contributes	
  significantly	
  
to	
  the	
  development	
  of	
  arch	
  form	
  
and	
  size	
  and	
  dental	
  occlusion,	
  
there	
  are	
  still	
  a	
  lot	
  of	
  occlusal	
  simi-­‐
larities	
  between	
  twin	
  A	
  and	
  B.	
  De-­‐
spite	
  the	
  assumption	
  that	
  genetics	
  
is	
  less	
  involved	
  in	
  the	
  lower	
  half	
  of	
  
the	
  face,	
  both	
  twins	
  present	
  with	
  
shifted	
  midlines	
  yet	
  maintain	
  a	
  
class	
  I	
  occlusal	
  relationship.	
  The	
  
only	
  striking	
  dissimilarities	
  that	
  
can	
  be	
  observed	
  is	
  that	
  there	
  is	
  
spacing	
  between	
  the	
  mandibular	
  
anterior	
  teeth	
  of	
  twin	
  B	
  whereas	
  
that	
  space	
  is	
  closed	
  in	
  twin	
  A	
  with	
  
the	
  cervical	
  necks	
  of	
  the	
  mandibu-­‐
lar	
  incisors	
  tipped	
  more	
  mesially.	
  
The	
  gingival	
  margins	
  also	
  appear	
  
to	
  be	
  more	
  rounded	
  in	
  twin	
  A	
  and	
  
more	
  pointed	
  in	
  twin	
  B.	
  Environ-­‐

mental	
  factors	
  such	
  
as	
  differences	
  in	
  
tooth	
  brushing	
  
technique	
  is	
  a	
  plau-­‐
sible	
  explanation	
  
for	
  this.	
  

Assessing	
  
the	
  bitewing	
  radio-­‐
graphs	
  between	
  
the	
  two	
  siblings,	
  
the	
  presence	
  of	
  
existing	
  restora-­‐
tions	
  was	
  used	
  to	
  
determine	
  caries	
  
susceptibility.	
  
Based	
  on	
  the	
  radi-­‐
ographs,	
  both	
  sib-­‐
lings	
  have	
  three	
  
restorations	
  with	
  
twin	
  A	
  having	
  res-­‐
torations	
  on	
  num-­‐
bers	
  2	
  (MO),	
  19	
  
(O),	
  and	
  20	
  (endo-­‐

dontic	
  treatment).	
  Twin	
  B	
  has	
  res-­‐
torations	
  on	
  numbers	
  3	
  (O),	
  19	
  
(O),	
  and	
  31	
  (O).	
  As	
  the	
  presenta-­‐
tion	
  of	
  carious	
  lesions	
  follows	
  a	
  
multifactorial	
  causation	
  that	
  relies	
  
on	
  the	
  balance	
  between	
  the	
  host	
  
(protective	
  mechanisms	
  like	
  sali-­‐
vary	
  flow	
  rate)	
  and	
  environmental	
  
factors	
  (diet	
  and	
  indigenous	
  bacte-­‐
rial	
  flora),	
  it	
  would	
  
not	
  be	
  a	
  surprise	
  if	
  
the	
  twins	
  differed	
  in	
  
caries	
  presentation	
  
as	
  genetic	
  similari-­‐
ties	
  alone	
  cannot	
  
determine	
  caries	
  
risk.	
  The	
  similarities	
  
seen	
  in	
  this	
  case	
  can	
  
be	
  attributed	
  to	
  
growing	
  in	
  the	
  same	
  
household	
  with	
  
similar	
  habits	
  in	
  di-­‐

eting	
  and	
  oral	
  hygiene.	
  This	
  may	
  
not	
  be	
  the	
  case	
  if	
  the	
  siblings	
  were	
  
separated	
  at	
  birth.	
  It	
  is	
  also	
  intri-­‐
guing	
  to	
  note	
  that	
  the	
  twins	
  pre-­‐
sent	
  with	
  differences	
  in	
  mandibu-­‐
lar	
  third	
  molar	
  formation.	
  While	
  
twin	
  A	
  retained	
  his	
  third	
  molars	
  to	
  
the	
  age	
  of	
  23,	
  twin	
  B	
  is	
  congenital-­‐
ly	
  missing	
  number	
  32.	
  Also	
  as	
  a	
  
child,	
  twin	
  B’s	
  number	
  18	
  was	
  se-­‐
verely	
  broken	
  down	
  by	
  caries	
  that	
  
it	
  was	
  extracted	
  and	
  number	
  17	
  
was	
  allowed	
  to	
  erupt	
  into	
  its	
  
place.	
  Moreover,	
  the	
  root	
  tips	
  on	
  
number	
  17	
  are	
  divergent	
  com-­‐
pared	
  to	
  twin	
  B’s,	
  which	
  is	
  notice-­‐
ably	
  convergent	
  apically.	
  This	
  sup-­‐
ports	
  the	
  idea	
  that	
  third	
  molars	
  
are	
  very	
  susceptible	
  to	
  develop-­‐
mental	
  variation	
  despite	
  identical	
  
genetics,	
  which	
  places	
  importance	
  
on	
  environmental	
  influences.	
  In-­‐
traoral	
  pictures	
  in	
  figure	
  4	
  further	
  
reveal	
  that	
  twin	
  A	
  possesses	
  a	
  
mandibular	
  torus	
  behind	
  number	
  
21.	
  Twin	
  B,	
  on	
  the	
  other	
  hand,	
  
possesses	
  bilateral	
  mandibular	
  tori	
  
behind	
  both	
  premolars	
  (#21	
  and	
  
#27).	
  Mandibular	
  tori	
  are	
  com-­‐
monly	
  present	
  early	
  in	
  adult	
  life	
  
and	
  are	
  associated	
  with	
  several	
  
factors	
  including	
  bruxism,	
  local	
  
stresses,	
  and	
  genetic	
  influences.	
  In	
  



Assessment	
  of	
  dentofacial	
  varia1ons	
  in	
  monozygo1c	
  twins	
  

Vol	
  5,	
  No	
  1	
  (2017)	
  	
  	
  	
  DOI	
  10.5195/d3000.2017.76	
  

	
  http://dentistry3000.pitt.edu	
  

this	
  case,	
  the	
  unilateral	
  mandibu-­‐
lar	
  torus	
  may	
  indicate	
  that	
  twins	
  A	
  
isn’t	
  occluding	
  evenly	
  if	
  he	
  is	
  brux-­‐
ing	
  on	
  a	
  normal	
  basis.	
  	
  

When	
  comparing	
  twins	
  
where	
  genetic	
  factors	
  are	
  con-­‐
trolled	
  for,	
  one	
  can	
  shift	
  the	
  focus	
  
towards	
  other	
  factors	
  that	
  may	
  
cause	
  dissimilarities	
  between	
  
identical	
  siblings,	
  which	
  includes	
  
epigenetic	
  factors,	
  maternal	
  varia-­‐
bles,	
  and	
  intrauterine	
  forces.	
  Epi-­‐
gentics	
  refers	
  to	
  DNA	
  methylation,	
  
acetylation,	
  phosphorylation,	
  
ubiquitination,	
  SUMOylation	
  and	
  
histone	
  modifications	
  that	
  reversi-­‐
bly	
  alter	
  DNA	
  structure	
  without	
  
changes	
  to	
  the	
  DNA	
  sequence.	
  
These	
  changes	
  accumulate	
  over	
  
time	
  as	
  they	
  are	
  transmitted	
  
through	
  mitosis.	
  While	
  de	
  novo	
  
methylation	
  by	
  DNA	
  methyltrans-­‐
ferase	
  targets	
  cytosine	
  bases	
  
without	
  apparent	
  specificity,	
  dele-­‐
tion	
  of	
  DNA	
  methyltransferase	
  
genes	
  (DMNT1)	
  in	
  mice	
  causes	
  
global	
  demethylation	
  and	
  apopto-­‐
sis	
  [7].	
  This	
  shows	
  how	
  there	
  is	
  a	
  
certain	
  randomness	
  that	
  can	
  have	
  
far	
  reaching	
  effects,	
  which	
  may	
  
lead	
  to	
  phenotypic	
  differences	
  be-­‐
tween	
  twins.	
  The	
  earlier	
  the	
  zy-­‐
gote	
  splits,	
  the	
  sooner	
  twins	
  de-­‐
velop	
  independently,	
  with	
  even	
  
the	
  slightest	
  DNA	
  modification	
  
having	
  the	
  potential	
  to	
  generate	
  
drastic	
  developmental	
  conse-­‐
quences	
  in	
  later	
  periods.	
  While	
  the	
  
etiology	
  of	
  epigenetic	
  changes	
  
needs	
  further	
  study,	
  there	
  is	
  a	
  
connection	
  between	
  methylation	
  
and	
  chemical	
  exposure,	
  which	
  may	
  
translate	
  to	
  an	
  attempt	
  at	
  envi-­‐
ronmental	
  adaptation	
  [8].	
  A	
  study	
  
to	
  assess	
  the	
  extent	
  of	
  DNA	
  meth-­‐
ylation	
  and	
  histone	
  acetylation	
  in	
  

the	
  genomes	
  of	
  40	
  pairs	
  of	
  
monozygotic	
  twins	
  found	
  that	
  epi-­‐
genetic	
  profiles	
  were	
  almost	
  iden-­‐
tical	
  in	
  65%	
  of	
  the	
  twin	
  pairs	
  and	
  
significant	
  differences	
  in	
  the	
  re-­‐
maining	
  35%	
  of	
  twin	
  pairs	
  [9].	
  Ac-­‐
cordingly,	
  the	
  amount	
  of	
  epigenet-­‐
ic	
  differences	
  was	
  directly	
  corre-­‐
lated	
  to	
  the	
  age	
  of	
  the	
  twins	
  and	
  
the	
  amount	
  of	
  time	
  co-­‐twins	
  spent	
  
apart.	
  As	
  such,	
  epigenetics	
  may	
  
play	
  a	
  huge	
  role	
  in	
  why	
  twins	
  A	
  
and	
  B	
  start	
  to	
  look	
  progressively	
  
different	
  as	
  they	
  age	
  in	
  figure	
  1.	
  

Intrauterine	
  factors	
  have	
  
also	
  been	
  suspected	
  to	
  play	
  a	
  role	
  
in	
  phenotypic	
  differences	
  between	
  
twins,	
  especially	
  in	
  regards	
  to	
  in-­‐
trauterine	
  special	
  constraint,	
  
which	
  are	
  common	
  during	
  twin	
  
fetal	
  development	
  and	
  may	
  also	
  
lead	
  to	
  deviations	
  in	
  facial	
  devel-­‐
opment	
  between	
  twins.	
  This	
  is	
  de-­‐
picted	
  in	
  one	
  study	
  in	
  which	
  re-­‐
straint	
  stress	
  was	
  applied	
  to	
  a	
  
group	
  of	
  pregnant	
  rat	
  study	
  mod-­‐
els	
  to	
  determine	
  the	
  extent	
  of	
  any	
  
changes	
  in	
  craniofacial	
  growth	
  
patterns	
  in	
  rat	
  offspring	
  that	
  in-­‐
trauterine	
  stresses	
  elicited	
  [10].	
  
The	
  prenatally	
  stressed	
  group	
  ex-­‐
perienced	
  increases	
  in	
  anterior	
  
cranial	
  base	
  length	
  and	
  viscer-­‐
ocranium	
  measures	
  with	
  back-­‐
ward	
  rotation	
  of	
  the	
  midface	
  and	
  
decreased	
  flattening	
  of	
  the	
  cranial	
  
vault.	
  In	
  this	
  case	
  prenatal	
  chronic	
  
stress	
  ultimately	
  promoted	
  endo-­‐
chondral	
  growth	
  in	
  the	
  cranial	
  
base	
  and	
  nasal	
  septum.	
  	
  

Finally,	
  maternal	
  variables	
  
also	
  play	
  a	
  key	
  role	
  in	
  difference	
  in	
  
dentofacial	
  development.	
  The	
  ef-­‐
fects	
  from	
  maternal	
  exposure	
  to	
  
nitrosatable	
  drugs,	
  fertility	
  treat-­‐

ments,	
  and	
  nutrition	
  intake	
  such	
  
as	
  folic	
  acid	
  intake	
  may	
  lead	
  to	
  ep-­‐
igenetic	
  changes	
  that	
  are	
  distrib-­‐
uted	
  unequally	
  to	
  developing	
  
twins	
  in	
  utero,	
  potentially	
  affect-­‐
ing	
  dentofacial	
  formation.	
  Folic	
  
acid	
  consumption	
  for	
  example	
  af-­‐
fects	
  neural	
  tube	
  closure,	
  which	
  in	
  
turn	
  impacts	
  brain	
  and	
  craniofacial	
  
structures	
  later	
  on	
  in	
  development	
  
[11].	
  

In	
  conclusion,	
  this	
  study	
  
brings	
  attention	
  to	
  the	
  genetic,	
  
epigenetic,	
  as	
  well	
  as	
  the	
  envi-­‐
ronmental	
  impacts	
  on	
  develop-­‐
ment	
  and	
  allows	
  one	
  to	
  fully	
  ap-­‐
preciate	
  the	
  multifactorial	
  forces	
  
of	
  this	
  process.	
  This	
  can	
  aid	
  in	
  pa-­‐
tient	
  education	
  in	
  terms	
  of	
  what	
  
can	
  and	
  can’t	
  be	
  definitively	
  
passed	
  down	
  to	
  the	
  offspring.	
  
While	
  genetics	
  are	
  often	
  the	
  prime	
  
suspect	
  in	
  rationalizing	
  phenotypic	
  
manifestations,	
  it	
  is	
  important	
  for	
  
patients	
  to	
  be	
  aware	
  of	
  other	
  envi-­‐
ronmental	
  factors	
  that	
  occur	
  after	
  
conception	
  that	
  may	
  also	
  ulti-­‐
mately	
  influence	
  dentofacial	
  
presentations.	
  	
  

References	
  

1.	
  Horowitz	
  SL,	
  Osborne	
  RH,	
  De-­‐
George	
  FV.	
  A	
  cephalometric	
  study	
  
of	
  craniofacial	
  variation	
  in	
  adult	
  
twins.	
  Angle	
  Orthod.	
  1960;30:1–5.	
  

2.	
  Cassidy	
  KM,	
  Harris	
  EF,	
  Tolley	
  EA,	
  
Keim	
  RG.	
  Genetic	
  influence	
  on	
  
dental	
  arch	
  form	
  in	
  orthodontic	
  
patients.	
  Angle	
  Orthod.	
  1998	
  
Oct;68(5):445-­‐54.	
  PubMed	
  PMID:	
  
9770103.	
  

3.	
  Lundström	
  A.	
  Nature	
  versus	
  
nurture	
  in	
  dento-­‐facial	
  variation.	
  



Assessment	
  of	
  dentofacial	
  varia1ons	
  in	
  monozygo1c	
  twins	
  

Vol	
  5,	
  No	
  1	
  (2017)	
  	
  	
  	
  DOI	
  10.5195/d3000.2017.76	
  

	
  http://dentistry3000.pitt.edu	
  

Eur	
  J	
  Orthod.	
  1984	
  May;6(2):77-­‐
91.	
  PubMed	
  PMID:	
  6587973.	
  

4.	
  Sognnaes	
  RF,	
  Rawson	
  RD,	
  Gratt	
  
BM,	
  Nguyen	
  NB.	
  Computer	
  com-­‐
parison	
  of	
  bitemark	
  patterns	
  in	
  
identical	
  twins.	
  J	
  Am	
  Dent	
  Assoc.	
  
1982	
  Sep;105(3):449-­‐51.	
  PubMed	
  
PMID:	
  6957451.	
  

5.	
  Curtner	
  RM.	
  Predetermination	
  
of	
  the	
  adult	
  face.	
  Am	
  J	
  Or-­‐
thod.	
  1953;39:201–217	
  

6.	
  Hunter	
  WS.	
  A	
  study	
  of	
  the	
  in-­‐
heritance	
  of	
  craniofacial	
  charac-­‐
teristics	
  as	
  seen	
  in	
  lateral	
  cephalo-­‐
grams	
  of	
  72	
  like-­‐sexed	
  twins.	
  Rep	
  
Congr	
  Eur	
  Orthod	
  Soc.1965;41:59-­‐
70.	
  PubMed	
  PMID:	
  5222375.	
  

7.	
  Singh	
  SM,	
  Murphy	
  B,	
  O'Reilly	
  R.	
  
Epigenetic	
  contributors	
  to	
  the	
  dis-­‐
cordance	
  of	
  monozygotic	
  twins.	
  
Clin	
  Genet.	
  2002	
  Aug;62(2):97-­‐
103.	
  Review.	
  PubMed	
  
PMID:12220446.	
  

8.	
  Poulsen	
  P,	
  Esteller	
  M,	
  Vaag	
  A,	
  
Fraga	
  MF.	
  The	
  epigenetic	
  basis	
  of	
  
twin	
  discordance	
  in	
  age-­‐related	
  
diseases.	
  Pediatr	
  Res.	
  2007	
  
May;61(5	
  Pt	
  2):38R-­‐42R.Review.	
  
PubMed	
  PMID:	
  17413848.	
  

9.	
  Fraga	
  MF,	
  Ballestar	
  E,	
  Paz	
  MF,	
  
Ropero	
  S,	
  Setien	
  F,	
  Ballestar	
  ML,	
  
Heine-­‐Suñer	
  D,	
  Cigudosa	
  JC,	
  Uri-­‐
oste	
  M,	
  Benitez	
  J,	
  Boix-­‐Chornet	
  M,	
  
Sanchez-­‐Aguilera	
  A,	
  Ling	
  C,	
  Carls-­‐
son	
  E,	
  Poulsen	
  P,	
  Vaag	
  A,	
  Stephan	
  
Z,	
  Spector	
  TD,	
  Wu	
  YZ,	
  Plass	
  C,	
  Es-­‐
teller	
  M.	
  Epigenetic	
  differences	
  
arise	
  during	
  the	
  lifetime	
  of	
  
monozygotic	
  twins.	
  Proc	
  Natl	
  Acad	
  
Sci	
  U	
  S	
  A.	
  2005	
  Jul	
  
26;102(30):10604-­‐9.	
  PubMed	
  

PMID:	
  16009939;	
  PubMed	
  Central	
  
PMCID:	
  PMC1174919.	
  

10.	
  Aminabadi	
  NA,	
  Behroozian	
  A,	
  
Talatahari	
  E,	
  Samiei	
  M,	
  Sadigh-­‐
Eteghad	
  S,	
  Shirazi	
  S.	
  Does	
  prenatal	
  
restraint	
  stress	
  change	
  the	
  cranio-­‐
facial	
  growth	
  pattern	
  of	
  rat	
  off-­‐
spring?	
  Eur	
  J	
  Oral	
  Sci.	
  2016	
  
Feb;124(1):17-­‐25.	
  doi:	
  
10.1111/eos.12230.	
  PubMed	
  
PMID:	
  26620628.	
  

11.	
  Kappen	
  C.	
  Modeling	
  anterior	
  
development	
  in	
  mice:	
  diet	
  as	
  
modulator	
  of	
  risk	
  for	
  neural	
  tube	
  
defects.	
  Am	
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