GENETICS IN

ORTHODONTICSPrepared by : Dr. ALI WAQAR

FCPS – II Resident OrthodonticsUCMD UOL

Supervised by : Dr. SAAD ASADAssociate Professor of Orthodontics

UCMD UOL

INTRODUCTION

The relative influence of genetics and environmental factors in the etiology of

malocclusion has been a matter of discussion, debate & controversy in

orthodontic literature

Genetic mechanisms are clearly predominant, but environment is also thought to influence dentofacuial morphology post natally.

The key to determination of etiology of malocclusion & its treatability 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.

BASIC TERMINOLOGIES Genotype : The genetic makeup of an organism

Phenotype : External visible appearance

Alleles : A pair of genes controlling the same character and located at the same locus in the homologous chromosomes

Homozygote : Individual carrying identical genes for a particular character

Heterozygote : Individual carrying non identical genes for particular character

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

Recessive : If 2 copies of the defective gene are required for expression of the trait

TOOTH SIZE, HYPODONTIA & DENTAL ROOT DEVELOPMENT

Hypodontia may occur without a family history, although it is often familial

It can also occur as part of a syndrome like Ectodermal Dysplasia

Genetic factors play a major role in this case with autosomal dominant, autosomal recessive and X-Linked multifactorial inheritance being reported

MSX-1 & PAX9 Genes involved in dentition patterening have been found to be involved in non syndromic autosomal dominant Hypodontia

LTBP3 gene which involves short stature, increased bone density in autosomal recessive hypodontia

Solitary Midline Maxillary Central Incisor Syndrome :

This heterogenous condition may include other midline abnormalities of the brain and other structures, can be due to mutation in SONIC HEDGEHOG GENE, SIX3 Gene.

ENVIRONMENTAL & GENETIC INFLUENCES ON BILATERAL SYMMETRY

Directional Asymmetery : Occurs when development on one side is different from that of the other during normal development, e.g Human Lung

Anti Symmetry : Occurs when one side is larger than the other

Fluctuating Asymmetry : Observed in primary and permanent dentition

GENETIC FACTORS & EXTERNAL APICAL ROOT RESORPTION

Degree and severity of EARR associated with orthodontics is multifactorial.

It involves host & environmental factors.

EARR exists in those individuals who have not received Orthodontic treatment.

Individuals with bruxism, chronic nail biting, anterior open bites and tongue thrust, all show increased extent of EARR before initiating orthodontic treatment.

EARR is also increased as consequence of orthodontic mechanical loading

Orthodontic biomechanics has been found to account for 1/10 to 1/3 of total variation in EARR

There is considerable variation in EARR associated with orthodontic treatment, indicating predisposition & multifactorial etiology

Retrospective twin study found evidence for both genetic & environmental factors influencing EARR

Variation in Interleukin-1B gene in orthodontically treated individuals accounts for 15% of variation in EARR

Although this genetic marker is associated with the trait, there are patients who have the marker but fail to present EARR, so the predictive value of this marker is limited by itself.

Iwasaki et al, found differences in ratio of IL-1B & IL-1RA in crevicular fluid of patients undergoing canine retraction.

This supports the hypothesis that bone modeling in part by IL-1B can be factor in EARR

Evidence suggests TNFRSF11A locus associated with EARR.

TNFRSF11A gene codes for RANK, part of osteoclast activation pathway

Future estimation of susceptibility to EARR will likely require the analysis of several genes

PAIN PERCEPTION & TEMPOROMANDIBULAR DYSFUNCTION

TMD classified as somatic & neuropathic

Genetic factors play role in TMD by influencing variation in pain perception, production of inflammatory cytokines etc from genes expressed in TMJ

Family aggregation studies have failed to identify genetic influence on TMD

Zubeitta et al, reported a gene encoding for enzyme catechol-O-methyl-transferase (COMT) is associated with decreased pain mechanism in CNS

Slade et al, TMD onset was 2.5 times greater in subjects who had HPS or APS haplotypes based on COMT genetic variation

SUMMARY Contrary to the presumption that malocclusions

caused by genetic cause are less amenable to treatment than those of enviornmental cause

Change in enviromental factors = change in polygenic trait

The capacity of an individual to respond to a change in environment influenced by genetic factors is of more importance clinically than the relative influence of genetic variation has on phenotypic variation before treatment