Role of genetics in
the etiology of
INDIAN DENTAL ACADEMY
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The relative influence of genetics
and environmental factors in the
etiology of malocclusion has been a
matter of discussion, debate &
controversy in the orthodontic
Genetic mechanisms are clearly
predominant – embryo, but
environment is also thought to
influence dento facial morphology post
natally. The key to determination of
etiology of malocclusion & its
treatibility lies in the ability to
differentiate the effect of genes &
environment in the cranio facial
skeleton in a particular individual.
Our ability to do this is limited by
our lack of knowledge on the genetic
mechanisms, that control growth and
lack of scientific evidence for the
influence of environmental factors on
human cranio facial morphogenesis.
Genotype – The genetic make up of
Phenotype – The external visible
appearance of an organism.
Alleles/Allelomorphs – A pair of
genes controlling the same character
and located at the same locus in the
Homozygote – Individual carrying
identical genes for a particular
character ( HH / hh )
Heterozygote – Individual carrying
non identical genes for a particular
character ( Hh )
Dominant – If a trait or disease
manifests itself when the affected
person carries only one copy of the
gene responsible, along with one
normal allele –dominant ( Dd )
Recessive – If two copies of the
defective gene are required for
expression of the trait – recessive ( ee )
Complementary genes – Two or more
dominant genes interact with one another to
produce a character ; but one cannot produce
the character in the absence of the other.
Supplementary genes – Two
independent pair of dominant genes, which
interact in such a way that each dominant
gene produces its effect when the other is
not present. When the two join - ?
Pleiotropism – The production of
many characters by a single pair of
Polygenes – Two or more non
allelic genes controlling single
quantitative character ( skin ) in a
Genic interaction – Expression of a
character by interaction of more than
one pair of genes-Allelic or Non Allelic
Sex linked gene – The genes
controlling body characters located on
the sex chromosomes. Most are
Continuous variation – One that is
not separable into discrete classes.
Determined by multi genic inheritance.
Discontinuous variation – Discrete
classes are easily recognized.
Why were they carried out ?
Concordant and Discordant twins?
1. Identical Twins Similar character
2. Fraternal Twins Different genotype
3. Siamese Twins First time in Siam
The frequency of MZ twins – 3.5 – 4
DZ twins – 3.5 – 18 per thousand
DZ & not MZ twinning –
Inheritance of DZ twinning –
confined to the female line
Determination of zygosity
The oldest way – Facial appearance
Based on hair colour & type, ear
form, tongue roll &
Tests on facial similarity &
hematological investigations usually
To determine zygosity at birth;
Protein enzyme analysis
For single gene trait – Monozygotic
concordance rate – 100 %. For DZ twins
- < this & equal to that in siblings.
For multifactorial traits – Rate in
MZ twins although less than 100%
exceeds rate in DZ twins.
In cleft studies ;
MZ - Concordance rate CL – 35%, CP – 26%
DZ ; CL – 5%, CP – 6%
What does this indicate ?
It tries to identify the genetic
component of disease, its mode of
inheritance and its distribution among
a population. It enables the study of
genetic linkage (?) & association (?)
Penetrance – The percentage of
individuals expressing the character for
a particular genotype ( complete /
Expressivity – The variation in
degree of expression of a particular
gene ( partial & zero expressivity ).
Class II div 1 Malocclusion
Investigations – Mand is
significantly retruded & overall mand
length reduced. Higher correlation b/w
patient & immediate family members.
Environmental factors ;
Soft tissue – L incisor.
Class II div 2
Markovic – 1992 -48 twin pairs
MZ – 100% concordance rate.
DZ – 90% were discordant.
This is a strong evidence to quote
genetics as a main etiologic factor .
Famous example –Hapsburg jaw.
Strohmayer – 1937 – autosomal
Schulze & Weize –concordance rate
in MZ twins 6 times higher than DZ .
Polygenic hypothesis as the
primary cause of mand prognathism.
A wide range of environmental
Congenital anatomic defects
Influence on tooth no & size
Osborne et al – 1958 – twin studies
– crown dimensions – heredity
Clinical evidence – congenital
absence & tooth size reduction –
Tooth size fits the polygenic multi
Super numerary tooth
Most frequently seen –
premaxillary region – male predilection
They are most commonly seen in
parents & siblings of patients.
Sugaku – 1963 – multi factorial.
Study of children with missing
teeth – half of their siblings & parents
also had missing teeth.
Markovic – 1982 – high rate of
concordance for MZ, while DZ were
Single autosomal dominant gene
with incomplete penetrance.
Abnormal tooth shape
Alvesalo & Portin – 1969 – missing
and malformed laterals – common gene
Peg shaped to missing teeth –
familial trends, female preponderance
& association with other dental
anomalies – misssing teeth, ectopic
canines, transposition – polygenic.
Ectopic maxillary canines
Various studies – genetic tendency.
Peck – 1994 – concluded palatally
ectopic canines were an inherited trait.
Submerged primary molars
Most often in mand arch.
Siblings– likely to be affected in
18% of cases, high concordance in MZ
twins – indicating a genetic component.
Associated with other anamolies –
may encompass diff manifestation of
same syndrome – incomplete
penetrance & variable expressivity
The clinical significance of the
inheritance of certain dental anomalies
is that clinicians should be vigilant in
the expectation that clinical or
radiographic evidence of one anomaly
should alert them to the possibility of
other defects in the same individual or
other family members.
In clinical orthodontics it must be
appreciated that each maloccusion
occupies its own distinctive slot in the
genetic/environmental spectrum and
therefore the diagnostic goal is to
determine the relative contribution of
genetics and environment
The greater the genetic component,
the worse the prognosis for a successful
outcome by means of orthodontic
intervention. If dento facial structure &
malocclusion are primarily genetic e.g.
severe mand prognathism or
endogenous tongue thrust, then
treatment wll either be palliative or
Are known to play a role in
patterning the embryonic development.
These can be regarded as master
genes of the head and face controlling
patterning, induction, programmed cell
death & epithelial mesenchymal
interaction during development.
Of particular interest – Hox group,
Msx 1 & Msx 2, Dlx (distaless),
The proteins encoded –
transcription factors (?)
At cellular level – The growth
factor family, the
steroid/thyroid/retinoic acid super
Molecular genetics in
Mesenchymal molecules and their
receptors – mediators. Bone morpho
genetic proteins BMP2, 4 & 7 mRNAs
shift. Tooth development and shape is
regulated by FGF 8 & FGF 9 via
downstream factors MSX 1 & PAX 9.
Msx 1 & Msx 2 - mesenchymal
interactions – initiation, developmental
position (Msx1) & further development
Pax 9 – tooth morphogenesis.
BMPs – growth factor family ( BMP
5 – endochondral osteogenesis, BMP 7 –
Genetically heterogenous disorder.
Two amelogenes – AMGX &
It is likely that mutations in several
genes may be involved in the etiology
of diff forms of autosomally inherited
While phenotype is inevitably the
result of both genetic & environmental
factors, there is irrefutable evidence for
a significant genetic influence in many
dental & occlusal variables.
The influence of genetics however
varies according to the trait under
consideration and in general remains
poorly understood. More precise
research tools and methods are
required to improve knowledge &
understanding, which in turn is a pre
requisite to the appreciation of the
potential for genetic and environmental
manipulation in orthodontic therapy.
The fight between
environment as a
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Leader in continuing dental education