CHAPTER 17

ppt / discussion

molecular blueprint

over 3 billion nucleotides of DNA, housing approximately 30,000 genes

46 chromosomes (23 pairs: 22 autosomes, 1 pair of sex chromosomes)

gene expression dictates cellular function, carefully regulated by time of development and cell type

a mutation or chromosomal disruption (like trisomy 21) throws the tightly regulated dosage of gene products off balance, resulting in compounding physical and developmental anomalies.

autosomal dominant

mechanism:

• vertical transmission

• only one defective gene copy needed

risk:

• 50% chance of passing to a child of either sex

key marker:

• incomplete penetrance (carriers may not manifest the disease)

ex:

• dentinogenesis imperfecta (DSPP gene)

• cleidocranial dysplasia

autosomal recessive

mechanism:

• two mutant gene copies required

• parents are typically asymptomatic carriers

risk:

• 25% chance of affected offspring

• 50% chance of carrier offspring

x-linked

mechanism:

• mutations on the X chromosome

• males manifest the disease (XY)

• females (XX) are usually carriers due to random X inactivation

risk:

• mothers pass to 50% of sons (affected)

• 50% of daughters (carriers)

• skips generations

ex:

• fragile X

• X-linked hypohidrotic ectodermal dysplasia

anatomy of anomaly

bifid uvula

lower lip pits

macroglossia

cleft lip/palate

low-set positioning

microdontia (small)

hypodontia (missing)

preauricular tags/pits

inner epicanthal folds

slanting palpebral fissure

ankyloglossia (tongue tie)

coloboma of the iris (cat eye)

hypertelorism (widely spaced)

hypertelorism

widely spaced

inner epicanthal folds

slanting palpebral fissures

coloboma of the iris (cat eye)

rule of three

if a child presents with three minor anomalies, there is a statistically massive increase in the probability of a major, hidden systemic anomaly (such as a brain or heart defect)

minor malformations:

• hair whorl

• aberrant oral frenulum

• preauricular pit → common in isolation

timeline of dental disruption

phase 1: initiation (early)

phase 2: morphodifferentiation (middle)

phase 3: histodifferentiation & mineralization (late)

phase 1: initiation (early)

disruptions here dictate quantity

clinical result:

• hypodontia (agenesis) or supernumerary teeth

phase 2: morphodifferentiation (middle)

disruptions here dictate size and shape

clinical result:

• macrodontia, microdontia

• taurodontism, dens invaginatus.

phase 3: histodifferentiation & mineralization (late)

defect:

• disruptions here dictate material integrity

clinical result:

• amelogenesis imperfecta

• dentinogenesis imperfecta

• enamel hypoplasia.

defects in agenesis & ectodermal

ectodermal dysplasia

isolated hypodontia

ectodermal dysplasia

genetics:

• EDA1, EDAR, TP63 (X-linked, AD, AR)

systemic:

• sparse hair, dry skin

• absence of sweat glands (overheating risk)

• absence/reduced sweat glands

dental:

• severe hypodontia

• conical teeth, deficient alveolar ridge

action:

• early fabrication of dentures

• avoid prolonged stabilization due to heat risk.

isolated hypoplasia

one of the most common developmental disorders.

prevalence: 1.6–9.6%, depending on population.

genetics:

• MSX1, PAX9, EDA, WNT10A (autosomal dominant)

systemic:

• none

• isolated finding (affects 1.6% to 9.6% of population)

dental:

• missing permanent lower second premolars or upper lateral incisors

action:

• monitor eruption

• consider orthodontics or implants as needed

defects in hard tissue matrix

amelogenesis imperfecta

dentinogenesis imperfecta

osteogenesis imperfecta

amelogensis imperfecta

genetics:

• ENAM, FAM83H, MMP-20 (AD, AR, x-linked)

systemic:

• normal general health

signature:

• enamel defects

• extreme wear sensitivity

• potential anterior open bite

dentinogenesis imperfecta

genetics:

• DSPP (autosomal dominant)

systemic:

• normal (unless linked to Ol)

signature:

• blue-gray/brown teeth

• severe primary dentition wear

• pulpal obliteration

osteogenesis imperfecta

genetics:

• COL1A1, COL1A2 (type I collagen defects)

systemic:

• bone fragility, blue sclera, short stature.

signature:

• occasional concurrent DI

• absolute contraindication for active/passive physical immobilization

defects in skeletal & arch anomalies

cleidocranial dysplasia

treacher collins syndrome

cleidocranial dysplasia

genetics:

• RUNX2 (autosomal dominant)

systemic:

• frontal bossing

• partial/complete absence of clavicles

dental:

• up to 60 supernumerary teeth causing massive impaction of permanent teeth

• requires multidisciplinary surgical/orthodontic timing.

hallmark:

• absence of clavicles

treacher collins syndrome

genetics:

• TCOF1 (autosomal dominant or sporadic)

systemic:

• lower eyelid coloboma

• conductive deafness

• malar/mandibular hypoplasia

dental:

• cleft palate

• severe micrognathia (intubation risk for general anesthesia)

hallmark:

• hypoplasia of 2 bones (malar, mandibular)

conditions that the cause is defect in FGFR2 mutation

apert syndrome

crouzon syndrome

—both syndromes are caused by mutations in the fibroblast growth factor receptor 2 (FGFR2) gene and are associated with advanced paternal age

apert syndrome

systemic:

• intellectual disability

• symmetric syndactyly (fusion) of hands and feet

craniofacial:

• acrobrachycephaly, cleft soft palate

• severely crowded teeth due to midface underdevelopment

crouzon syndrome

inheritance:

• autosomal dominant with variable expression

gene:

• FGFR2

general manifestations:

• usually normal intelligence

• conductive hearing loss

• cervical spine anomalies

• increased digital skull markings

• calcification of stylohyoid ligaments

• ocular proptosis (shallow orbits)

defects in chromosomal & systematic dynamics

down syndrome

fragile X syndrome

down syndrome

genetics:

• trisomy 21 (chromosomal).

systemic:

• cardiac anomalies (40%)

• intellectual disability, leukemia risk.

dental:

• elevated risk for severe periodontal disease

• crucial need to verify cardiac status for subacute bacterial endocarditis (SBE) prophylaxis before treatment.

fragile X syndrome

genetics:

• FMR1 (X-linked, DNA triplet repeat expansion).

systemic:

• autism (in 60%)

• macroorchidism

• intellectual disability

dental:

• macrocephaly and prognathism

• behavioral tolerance → primary challenge

• requires caregiver-focused oral hygiene training

systemic clues in the dental chair

williams-beuren syndrome

hypophosphatasia

williams-beuren syndrome

genetics:

• ELN, LIMK1, 7q11.23 deletion

the clues:

• hoarse voice

• extremely outgoing personality

• stellate (star-like) pattern in the iris

dental:

• hypersensitivity to sound requires environmental modification

• supravalvular aortic stenosis makes SBE prophylaxis screening mandatory

hallmark:

• stellate pattern in iris

hypophosphatasia

genetics:

• TNSALP (tissue-nonspecific alkaline phosphatase)

the clues:

• bone fragility, bowed extremities

dental:

• premature loss of primary incisors → very first sign of the disease

• teeth exfoliate fully intact with no root resorption due to a complete lack of cementum

orofacial cleft

clefts affect 1 in 600 newborns

etiology is a complex mix of:

• genetics (MSX1, IRF6)

• environment (maternal smoking, phenytoin, folate antagonists)

2 types of orofacial cleft

syndromic (van der woude syndrome)

isolated (nonsyndromic)

van der woude syndrome (syndromic)

genetics:

• IRF6, GRHL3 (autosomal dominant)

key differences:

• presence of lower lip pits alongside cleft lip/palate

• normal intelligence

isolated (nonsyndromic) orofacial clefts

inheritance:

• autosomal dominant

• non-mendelian with gene/environment interactions

genes:

• MSX1, TBX22, TP63, IRF6

dental/craniofacial:

• cleft lip with or without cleft palate

• can be:

  • isolated, syndromic

3 major types of amelogenesis imperfecta (AI)

hypoplastic amelogenesis imperfecta

hypocalcified amelogenesis imperfecta

hypomaturation amelogenesis imperfecta

hypoplastic amelogenesis imperfecta

quantity defect

results in reduced enamel thickness

caused by deficient enamel matrix formation

clinical appearance:

• generalized thin enamel with pits/grooves

hypomaturation amelogenesis imperfecta

low value amount of ameloblast

produces hypomineralized enamel

caused by defective crystal growth and mineralization during the maturation stage of enamel development

clinical appearance:

• mottled white-yellow-brown enamel that chips

• soft

hypocalcified amelogenesis imperfecta

quality defect

also produces hypomineralized enamel

caused by abnormal initiation of enamel crystallites followed by defective mineralization

clinical appearance:

• chalky yellow-brown enamel that wears rapidly

• very soft

dentinogenesis imperfecta (DGI)

discoloration results from abnormal dentin showing through translucent enamel

• clinical features:

  • discolored teeth → blue-gray or yellow-brown

  • prone to rapid wear, breakage, loss

• radiographic findings:

  • pronounced cervical constriction at the CEJ

  • small root structures that may appear:

    • sharp & tent peg-like

• management:

  • once significant enamel loss and rapid attrition begin:

    • full-coverage crowns → treatment of choice

3 types of dentinogenesis imperfecta (DGI)

DGI type I

DGI type II

DGI type III

both type II and type II are:

• autosomal dominant

• highly penetrant

dentinogenesis imperfecta type I

bone involvement, blue-sclera on eyes

occurs in people who have osteogenesis imperfecta

a genetic condition in which bones are brittle, causing them to break easily

dentinogenesis imperfecta type II

no bone involvement

not associated with a syndrome

most common type of dentinogenesis imperfecta

occurs in people without another inherited disorder

gene:

• DSPP (dentin sialophosphoprotein) gene

dentinogenesis imperfecta type III

shell tooth

generally the same as dentinogenesis imperfecta type II except initially have large pulp chambers that obliterate with age results to multiple pulp exposure

osteogenesis imperfecta

aka: brittle bone disease

• caused by mutations affecting:

  • type I collagen

  • proteins involved in fibrillogenesis

• general manifestations

  • bone fragility

  • short stature

  • normal intelligence

  • limb deformities

• craniofacial/Dental

  • triangular face

  • blue sclera

  • possible dentinogenesis imperfecta

  • delayed tooth eruption