genetics in dentistry

Question 1

how to assess genetic involvement in etiology

Answer 1

1) family history (pedigree)
2) medical history
- trauma, tumor, habits
3) correct diagnosis
- literature
4) previous treatment outcomes

Question 2

congenital anomalies of the teeth

Answer 2

1) anodontia
2) hypodontia
3) hyperdontia
4) microdontia
5) macrodontia
6) enamel dysplasia
7) dentin dysplasia
8) cementum dysplasia
9) pulp dysplasia
10) complex abnormalities of tooth structure
11) abnormalities of tooth shape
12) abnormalities of eruption
13) malalignment, malocclusion

Question 3

tooth development

Answer 3

1 )growth
- initiation
- proliferation
- morphodifferentiation
2) calcification
3) eruption
- before and after emergence
4) attrition

Question 4

prenatal tooth development

Answer 4

1) tooth develops from the ectoderm of embryonic stomodeum
- 5th and 6th week
- dental lamina develops
2) what develops?
- embryonic tooth buds (dental organs)
- dental papilla
- dental sac
- bell shaped dental organs
- dental lamina degenerates

Question 5

clinical diagnosis of congenital anomalies

Answer 5

1) 6 stages of development
- initiation
-proliferation
- histodifferentiation
- morphodifferentiation
- apposition
- maturation

Question 6

initiation

Answer 6

1) lack of development or abnormal development
- anodontia (6th week)
- absence of all primary and secondary teeth
2) disruption in focal areas and lack of initiation in these spots
- hypodontia
3) disruption in focal areas and overactivity of the lamina
- supernumerary teeth

Question 7

proliferation

Answer 7

1) separate tooth buds proliferate at their predetermined places
- interference with proliferation => hypodontia

Question 8

histodifferentiation

Answer 8

1) establishment of ameloblasts and odontoblasts
2) compromise of differentiation of inner dental epithelium
- odontoblast formation is not stimulated => arrest of tooth development
3) failure of proper differentiation of odontoblasts
- ameloblasts formation is not stimulated => no enamel is formed
4) abnormal differentiation
- abnormal dental structures
- poorly organized
- poorly formed

Question 9

morphodifferentiation

Answer 9

1) differential growth of parts of the dental organ is responsible for the basic size and shape of the teeth
2) abnormal morphodifferentiation
- microdontia
- macrodontia
- globodontia
- supernumerary cusps

Question 10

apposition

Answer 10

1) deposition of matrix of dentin and enamel
2) defects in predentin
- dentin dysplasia
3) insufficient enamel matrix
- enamel dysplasia, hypoplastic types
4) disruptions during mineralization
- enamel dysplasia, hypocalcified types

Question 11

maturation

Answer 11

1) maturation of the hard matrix follow appositional growth
2) interference with maturation
- enamel dysplasias, hypomature forms

Question 12

anodontia

Answer 12

1) anodontia
- congenital agenesis of all deciduous and all permanent teeth

Question 13

hypodontia

Answer 13

1) <6 teeth
- most prevalent dentofacial anomaly
- either syndromic or nonsyndromic

Question 14

oligodontia

Answer 14

1) congenital agenesis >6

Question 15

tooth angenesis

Answer 15

1) directly the developmental failure of tooth

Question 16

prevalence of CMT

Answer 16

1) most common
- #3 molar included - nonsyndromic occurred in 25% population
2) deciduous dentition
- 0.5-0.9%
3) permanent dentition excluding 3rd molars
- 1.6 to 9.6%

Question 17

syndromic

Answer 17

1) mutation renders protein nonfunctional

Question 18

nonsyndromic etiology

Answer 18

1) tooth development theories
- successive molecular interactions are involved
- Fgf, BMP, SHh
- alteration in one of more signalling pathways may affect dental development and cause hyodontia
2) tooth agenesis theories
- evolutional (shortening of arches)
- anatomic principle
- specific areas of the dental lamina are prone to environmental effects throughout tooth maturation
- places on initial fusion in embryological development

Question 19

nonsyndromic

Answer 19

1) mild deficiency of protein function
- genetic and environmental factors
2) several genes: important in the communication of dental tissues in the developing dentition

Question 20

formation of the dental lamina

Answer 20

1) in early embryonic development, the dental lamina initiates tooth development
- if the lamina is not formed or its early organization is abnormal, initiation will not occur and teeth will not develop at all (anodontia)
2) only a portion of the lamina is physically disrupted, initiation is disrupted in focal areas and only teeth in that area will not develop (hypodontia)

Question 21

nonsyndromic CMT genetic factors

Answer 21

1) strong genetic influence in hypodontia
- high heritability
2) TA of lateral incisors and premolars
- AD with incomplete penetrance and variable expressivity
3) TA of other teeth
- maybe polygenic, but more studies toward single gene mutations
4) present research on genes involved in tooth development (GWAS, signaling pathways, etc)

Question 22

genes in nonsyndromic CMT

Answer 22

1) over 300 genes are expressed in tooth morphogenesis
2) PAX9 (molars) and MSX1 (premolars) are most important in regulating TFs for mesenchymal/epithelial interactions
3) gene function is maintenance and regulation of Bmp4 expression in dental mesenchyme

Question 23

PAX9

Answer 23

1) important role in sequencing and signaling cascades between epithelial and mesenchymal cell layers
2) together with MSX1 maintenance of mesenchymal BMP4 expression
3) BMP4 downregulation
4) 60 mutations of this gene have been associated with non syndromic TA
- mostly molars
5) protein dysfunction haploinsufficiency
6) PAX9 mostly expressed in the neural crest derived mesenchyme
7) most common consequence of PAX9 is autosomal dominant nonsyndromic oligodontia

Question 24

PAX9 location

Answer 24

1) chromosome 14q13.3
2) 5 exons
2) 1st and 5th exons are important, which may have some mutations

Question 25

MSX1 gene

Answer 25

1) located on 4p16.2 2) 5 mutations in human OMIM 3) instructions for making protein that regulated activity of other genes 4) part of homeobox gene family - act in early development to control formation of body structures 5) critical for normal development of the teeth and other structures in the mouth 6) may be important for development for fingernails and toenails

Question 26

dental caries is caused by

Answer 26

1 )acidic environment that results from carb metabolism when sugars are introduced 2) multifactorial - enamel and dentin structure - immune response - salivary content and volume - oral microbiota - susceptibility genes- direct role of gene variants is inconsistent

Question 27

twin studies

Answer 27

1) monozygotic and dizygotic - heritability 0.2-0.85 - variation of caries experience - population or race-level genetic and environmental differences

Question 28

early childhood caries experience

Answer 28

1 )maternal health or obesity 2_ living in rural area 3) low socioeconomic status 4) less frequent tooth screens 5) sugary drinks

Question 29

GWAS studies

Answer 29

1) identified a number of susceptibility loci - MMP10, MMP14, MMP16, MPPED2, ACTN2, tuftlin and chromosomal regions with unknown function 2) AMELEX, AQP5, and ESRB appear to be a solid source of information for genetic association with caries

Question 30

genetic controls of periodontal disease

Answer 30

1) complex and multifactorial - shares more of a direct link with overall health than dental caries 2) risk factors such as smoking and diabetes can significantly contribute to its etiology 3 )heritability - periodontal disease has been estimated at around 0.5 although gene variant appears to vary according to population

Question 31

causes of periodontal disease

Answer 31

1 )several mechanisms - subgingival microbiome - genetic and epigenetics - behavioral and environmental - systemic health 2) two steps - genetic susceptibility and a bacterial challenge

Question 32

role in genetics in etiology of periodontal disease is

Answer 32

1) controlling periodontal structural integrity 2) affecting the host response to subgingival microbiota

Question 33

strongest susceptibility genes for perio

Answer 33

1) vitamin D receptor gene, VDR, IL-10, IL-1beta, IL-6, and immunoglobulin platelet receptor gene Tc-yRIIA

Question 34

malocclusions and dentofacial deformity

Answer 34

1) imbalance of position, size, shape, orientation of bone for the jaws 2) diarrangment of teeth 3) compromise aesthetics 4) 2% requires surgery

Question 35

prevalence of malocclusion

Answer 35

1) 30% have normal occlusion 2) 55% class I malocclusion 3) 15% class II 4) <1% class III

Question 36

environmental factors

Answer 36

1) prenatal period - teratogens - radiation - intra uterine fetal posture 2) natal factors - trauma to condylar regions 3) postnatal factors - traumatic injury to the mandible, TMJ - infection conditions - rheumatoid arthritis - abnormal function such as oral respiration, abnormal swallowing - habits such as thumb sucking prevent normal muscle activity

Question 37

genetic factors can cause

Answer 37

1) skeletal factors - class II malocclusion - class III malocclusion - cleft lip and palate other CA and sy 2) soft tissue factors 3) dental factors - missing teeth - too many teeth - impacted canines - misshapen teeth - maxillary midline diastema - root resorption - eruption abnormality

Question 38

etiology of malocclusions

Answer 38

1) in malocclusions - except if present in syndromes, it is always interaction of genetic and non-genetic factors! 2) multifactorial - polygenic inheritance - environmental factors: triggers, epigenetics 3) strong gentic influence - class III - class II division 2 4) nongenetics - thumb sucking - tongue thrusting

Question 39

pedigree of hapsburg dynasty

Answer 39

1) strong prognathism inherited in autosomal dominant patter 2) lots of inbreeding

Question 40

phenotype

Answer 40

1) genetic factors +environmental 2) heritability 0.5 - equal probability G and E 3) heritability 0.8 -much more genetic influence -ex mandibular prognathism 4) 0.3 - small genetic influence - open bite due to thumb sucking

Question 41

phenomics

Answer 41

1) pictures, casts, imaging 2) measurements

Question 42

geneomics

Answer 42

1)genes involved in development, malocclusions, missing teeth, syndromes

Question 43

phenotype and genotype interactions

Answer 43

1) intrauterine 2) postnatal - focusing on symptoms rather than etiology

Question 44

current knowledge of genetics of malocclusions

Answer 44

1) environmental + genetics 2) environmental - enlarged tonsil - nasal breathing difficulties - etc. 3) genetics - VEGF - IGF-1 - HOIX 3 region -chromosomal loci (1p36, 12p23) harbor genes that increase the likelihood of mandibular prognathism)

Question 45

class II and class I patients

Answer 45

1 )noggin gene - important for mandibular formation - homozygous for the rare allele on SNP rs1348322 - class I patients: EDA, XEDAR, and BMP2 - genes implicated in bone and cartilage development, muscle function, and tooth morphogenesis may be indicative for jaw and tooth size discrepancy

Question 46

class III patients

Answer 46

1) autosomal dominant 2) EBB41, MATN1, SSX2IP, 1p22-p36 locus - positive correlation with mandibular prognathism: COL2A1, MYO1H, TGFB3, LTBP2, chromosome 12q13-14 - variants within DUSP6 could account for class III due to maxillary hypoplasia

Question 47

oral cancer

Answer 47

1) subgroup of head and neck malignancies that develop at lip, tongue, salivary glands, gingiva, floor of mouth, oropharyx, buccal surfaces, others 2) several types of oral cancer 3) >90% are OCSCC 4) incidence and mortality rates are 3.3-5.9/100,000/year

Question 48

genetics and oral cancer

Answer 48

1) oral carcinogenesis is a multifactorial process that can alter the function of - oncogenes - tumor suppressor genes - other molecules 2) loss of tumor suppressor activity - increasing cellular proliferation - weakening cell cohesion - local infiltration and metastasis 3) 90% is OCSSC which is caused by genetic alteration - COX-2 - EpCAM - MMP-2.6

Question 49

common gene alterations in oral cancer

Answer 49

1) two important genes a) EGFR >30% (cell proliferation, growth) - mutation increased numbers of receptors and ligand independent signals b) p53 50-60% (cell cycle regulation) - maintains genome stability and DNA repair, so mutation causes issues