PR4 Genetic Basis of Hereditary Enamel and Dentine Disorders

Types of congenital malformations

Isolated: tooth malformations only

Syndromic: craniofacial or systemic malformations

Types of dental malformations

Hypodontia

Hyperdontia

Supernumeraries

Size/shape abnormalities

Mineralization abnormalities

Causes of non-syndromic malformations

unknown causes, environmental factors, genetic factors

Causes of syndromic malformations

related to chromosomal defects

Steps of tooth development

Initiation stage → Bud stage → Cap stage → Early Bell stage → Late Bell stage → Root formation stage

Hormones involved in tooth development (Initiation through Cap stage)

FGFs

BMP

EDA

WNT

MSX1

Activin

Hormones involved in tooth development (Early bell through root formation stage)

Enamel matrix proteins

DSPP

Collagen

Malformations during the Initiation and Bud stage

Tooth number abnormalities

Malformations during the Cap and Early Bell stage

Shape/size abnormalities

Malformations during the Late bell and Root formation stage

Hypomineralization

Hypermineralization

Hypodontia

Ectodermal Dysplasia; 7 in 1000 births

Mutations in:

• ectodysplasin A

• MSX1

• AXIN2

Most likely to be missing 3rd molars, 2nd premolars, maxillary lateral incisors

Typically autosomal dominant

Oligodontia

Hypodontia where more than 6 teeth are missing

Ectodysplasin A

gene that regulates ectodermal tissue growth

MSX1

multiple epithelial-mesenchymal interactions

AXIN2

related to apoptosis

most likely to cause oligodontia

Cleidocranial dysplasia

a type of hyperdontia

caused by RUNX2 mutation (FGF regulator in bone and teeth)

Features:

• clavicles missing

• mandible prognathic

• maxilla micrognathism

• frontal bossing

• supernumerary teeth

Gardner’s Syndrome

APC (tumor suppressing gene) mutation

creates multiple jaw osteomas that give a “cotton wool” appearance to the jaws

causes impacted and supernumerary teeth

Types of morphological (shape/size) anomalies

macrodontia

microdontia

peg shaped tooth

den invaginatus (invaginated odontia)

den evaginatus (Evaginated odontia)

teeth with this are susceptible to infection and syphilis

Amelogenesis imperfecta

1:700 to 1:1400 people affected

Mutations in enamel matrix genes:

• ameloblsatin

• enamelin

• tuftelin

• amelogenin

• FAM83H

Can be autosomal dominant (mutation in enamelin or FAM83H); autosomal recessive (ameloblastin mutation); X-linked dominant (amelogenin mutation)

defect in the mineralization of the enamel (teeth are yellow, bulky, and chalky)

Dentinogenesis imperfecta (DI)

1:6000 to 1:8000 people affected

defect in the mineralization of the dentin

teeth appear translucent and thin

Dentinogenesis imperfecta Type I

combined with osteogenesis imperfecta

caused by collagen gene mutation (COL1A1 and COL1A2)

80% autosomal dominant

20% autosomal recessive

Dentinogenesis imperfecta Type II & III

caused by dentin sialophosphoprotein (DSPP) mutation

autosomal dominant

Dentine Dysplasia

1:100000 people affected

2 Types: DD Type I, DD Type II

Dentine Dysplasia Type I

radicular dysplasia

caused by collagen (COL1A1 and COL1A2) mutations

autosomal dominant

*similar to DI type I

Dentine Dysplasia Type II

caused by dentin sialophosphoportein (DSPP) mutation

autosomal dominant but more complete penetration therefore more severe appearance that DI type II