3. Genetic Disorders of Teeth Flashcards
Tooth pathology
• ____
• Developmental
• ____
- Morphology
- ____
- Size
- ____
- Structure• Cleidocranial dysplasia > manifest with ____ teeth (number)
acquired genetic color number extra
Genetic disorders – tooth number
• Hypodontia
– Ectodermal dysplasia
– Hereditary oligodontia
* \_\_\_\_ - no teeth * \_\_\_\_ - few teeth (6+) * Diseases that cause phenotype are similar, but vary from patient to patient
Hypodontia
• ED > impairs ____ cells from forming > phenotype that’s characteristic: less hair, ____ glands may be impaired (hyponecrosis?), the teeth are ____ (fewer and may have complete absence of teeth); a change in tooth ____ and in ____
○ Enamel, dentin, pulp - everything is completely ____ - can be bonded and prepped normally
○ ____-like teeth
○ 135 diseases that fall in this category of ED
§ X-linked ED, and X-linked hypohydrotic > this patient on screen has
§ The sweating issue can be ____ > in order for body to breath you need sweat; it cools you off, and if you can’t sweat > body T continues to rise
□ Patients wear a specialized vest that keeps them ____
• HO > limited to a ____ phenotype
○ Gene defects that only relate to tooth development
○ Complicated treatments > but have ____ teeth than normal
§ One patient had molars were missing, and one patient had missing premolars
○ There is also a genetic basis, but the teeth were ____
§ If missing molar ____, it’s rare to miss these > likely to be this condition here
anodontia
oligodontia
epithelial sweat misshapen number structure normal peg life-threatening cool
dental
fewer
normal
congenitally
Genetic disorders – tooth number
• Hyperdontia
– Cleidocranial dysplasia
– Familial adenomatous polyposis
Hyperdontia
• Characterized by several extra teeth, erupted or unerupted
○ No discrimination to which tooth is extra in number
• These patients are also missing the ____; may be shorted and may have ____ skulls
• FAP > ____ syndrome
○ As young kid, will have ____ teeth radiographically
○ Colon that contains numerous benign tumors > risk of developing malignancy from having all the tumors > will develop colon cancer
§ Prophylactically had colon removed in order to improve treatment
* CD > if can put \_\_\_\_ together > missing clavicles, implies they have this disease; can diagnose in office * No known condition where they only have \_\_\_\_ teeth; they have something else going on with it
clavicles
bigger
gardner
extra
shoulder blades
extra
Hypodontia - Ectodermal dysplasia
• \_\_\_\_ group of diseases – AD, AR and X-linked • Defects in \_\_\_\_ structures • X-linked hypohidrotic ED – \_\_\_\_ gene
• Use term as disease name > genetically heterogeneous predisposition ○ X-linked form > only affects \_\_\_\_ § Mother has one of two alleles has a mutation, and son inherits with the Y from the father § Mutation in EDA gene > plays role in epithelial/ectodermal structure development > \_\_\_\_, tooth, skin and \_\_\_\_ gland development • Disease phenotype is same across all \_\_\_\_ that have this nomenclature
heterogeneous ectodermal EDA boys hair sweat diseases
Ectodermal dysplasia
• ____, abnormal nails, hypohidrosis
• Dental agenesis - ____, oligodontia
• Hypothricosis - less \_\_\_\_ • Hypohidrosis - less \_\_\_\_ • Very rarely anodontia • Treatment - do not treat, not a lot you can do therapeutically ○ Require more specialized care > \_\_\_\_, or through perio-prosth program
hypothrichosis hypodontia hair sweat prosthodontist
Genetic disorders- tooth number
* Radiograph reveals eight extra teeth * Patient had FAP - also had a history of \_\_\_\_ cancer * Patient is \_\_\_\_ because of all the restorations
colon
older
Hyperdontia- Cleidocranial dysplasia • RUNX2 – \_\_\_\_ – \_\_\_\_ stages of bone development – \_\_\_\_ stages of tooth development
* Caused by mutation in RUNX2 > particularly important in development of \_\_\_\_ * Mice who lack this protein > limited skeleton (tiny, all bones are affected) * Patient has \_\_\_\_ teeth, all shapes and sizes sitting within the jaw bone
transcription factor all late clavicles extra
Hyperdontia –
Familial adenomatous polyposis (Gardner syndrome)
• Autosomal \_\_\_\_ • Chromosome \_\_\_\_ -> \_\_\_\_ gene – APC regulates \_\_\_\_, targeting it for destruction • Clinical features – Intestinal \_\_\_\_ – \_\_\_\_ cancer – \_\_\_\_ teeth
* APC encodes a \_\_\_\_ protein > when lose the function of it, you prevent the breaks of tumor suppression > develop numerous tumors as go through development * B-catenin doesn't cause tumors > but plays a role in tooth development; if not present in proper form > \_\_\_\_ tooth development * Prone to benign bone tumor > \_\_\_\_ > multiple osteomas is pathognomonic for this syndrome; can diagnose based solely off the radiograph * Also get tooth tumors > \_\_\_\_ > benign tumor of tooth structure; not \_\_\_\_ but characteristic of disease • Each bump is a \_\_\_\_ tumor
dominant 5 APC b-catenin polyposis colon supernumerary
tumor suppressor uncontrolled osteoma odontoma pathognomonic benign
Genetic disorders – tooth shape
• Globodontia – \_\_\_\_ syndrome • Taurodontism – \_\_\_\_ syndrome • Radiculomegaly – \_\_\_\_ syndrome
• Changes in tooth shape are not common • Otodental syndrome - oto implies ear/hearing, and there's a dental phenotype ○ \_\_\_\_, and teeth have a \_\_\_\_-like appearance (not much \_\_\_\_ anatomy) ○ Only disease with this \_\_\_\_, and all teeth have similar
otodental tricho-dento-osseous oculo-facial-cardio-dental deaf globe occlusal morphology
Globodontism
• ____ molars
rounded
Taurodontism
• Taurodontism
○ Seen ____ (not seen with globo - one tooth can be circular due to ischemia; if seen all over then it’s ____)
○ Molar has a “____” (tauro = bull)
§ Teeth constrict cervically normally, but here, ____ down (no shape, curves, etc.) to the cervical portion of the tooth
§ Morphology extends apically down to the base of the tooth - ____ roots at the apex
○ Can see in any heathy patient you see in the clinic, doesn’t have to worry
§ Only worry when ____ teeth in same morphology
§ Syndromes that are characterized by several teeth having this morphology > also affect other ectodermal structures > the ____
• Tricho-dento-osseous syndrome > tricho (____), dento (tooth), and osseous (____)
○ Hair is ____ and it falls apart
○ Taurodontic teeth > integrity wise they’re ____, but morphologically abnormal
○ Changes to the bone
sporadically genetic bull-neck straight tiny multiple hair hair bone crinkly normal
• Radiculomegaly
○ Only one disease forms this > ____ syndrome
§ ____, face is affected (eyes are ____ spaced, bridge of nose is flat), ____ is affected and the dental phenotype
§ The dental phenotype is ____
□ Long roots of the ____ (both maxillary and mandibular)
○ ____ normal
§ Do an ____ after the fact
oculo-facial-cardio-dental blind widely heart pathognomonic canines structurally apicoectomy
Genetic disorders – tooth structure and substance
• Enamel – \_\_\_\_ • Dentin – \_\_\_\_ – Dentin dysplasia • Cementum – \_\_\_\_
• More commonly encountered diseases in practice (tooth structure and substance) • AI - affects only enamel production • DI, DD - affect only dentin • HP - affects cementum, but affects both \_\_\_\_ and cementum • This patient, 5 y.o, all teeth similarly affected and parents were normal > developed AI ○ Several clinical and genetic subtypes
amelogenesis imperfecta
dentinogenesi imperfecta
hypophosphatasia
bone
Amelogenesis imperfecta • Genetically heterogeneous – Autosomal \_\_\_\_ – Autosomal \_\_\_\_ – \_\_\_\_ • Hypoplastic • Hypomaturation • Hypocalcified • AMELX, ENAM, MMP20, KLK4, WDR72 and FAM83H genes
• Enamel has a complex biology/development > several proteins (listed at the bottom) > implicated in enamel development ○ Explains phenotypic variability and genetic variability of this syndrome • X-linked form > occurs in \_\_\_\_, can also occur in \_\_\_\_ also ○ Don’t memorize the genes, but know they're implicated
Know the ones for CD, gardners, and X-linked hypohydrotic dysplasia
dominant recessive x-linked boys females
Amelogenesis imperfecta
• 3 phenotypic basis:
○ Hypoplastic
§ Teeth are smaller, less ____
§ Pits on the enamel surfaces (shown here); not ____ for this syndrome, but if you see several that are pitted then you should think of this condition
§ Enamels ____ normal, no less prone to ____ than any other patient
○ Hypomaturation (next two slides) § Teeth are smaller; the enamel is produced in sufficient quantity, but it doesn't \_\_\_\_ properly □ Forms crystals during formation, the matrix calcifies □ If you don't produce enough \_\_\_\_, and then they don't mature/orient properly (if doesn't calcified properly it's hypocalcified) § \_\_\_\_, mottled looking teeth § Very weak - can easily be \_\_\_\_ down (\_\_\_\_, tooth brushing) □ More prone to \_\_\_\_ ○ Hypocalcified § Teeth take on \_\_\_\_h appearance, but the tooth are \_\_\_\_ sound § Prone to \_\_\_\_ § More difficult to diagnose > teeth take on a \_\_\_\_ chalky appearance § Affects both \_\_\_\_ and \_\_\_\_teeth, and all teeth are affected § Not effective to bond with \_\_\_\_ - cannot \_\_\_\_ the teeth, and they are difficult to treat
enamel
pathognomonic
caries
mature matrix yellow worn attrition caries
yellowish morphologically caries white deciduous permnanet composite etch
Amelogenesis Imperfecta
• A combination of two+ types ○ Here, both \_\_\_\_ and \_\_\_\_ ○ No hypoplastic > no \_\_\_\_in teeth
hypomature
hypocalcified
pits
Amelogenesis Imperfecta
• \_\_\_\_ the teeth look normal > only see that the enamel doesn't have the same radio opacity you see in healthy teeth ○ Do not see a strong \_\_\_\_ bt dentin and enamel (look homogeneous)
radiographically
distinction
Dentinogenesis imperfecta • Type 1 associated with \_\_\_\_ – \_\_\_\_, COL1A2 genes • Type 2 caused by \_\_\_\_ gene mutations – May be involved in \_\_\_\_ of dentin collagen
• Has a very different radiographic appearance - \_\_\_\_ may look the same (dentin may mimic enamel phenotypically) • OI > genetic disease ○ Mutations in type 1 collagen > helix of two proteins > COL1A1 and 1A2 § Upon mutation of one protein or the other > helix \_\_\_\_ > defective type 1 collagen production > used by HA to mineralize tooth structure > \_\_\_\_ fractures § Also role in tooth development via \_\_\_\_ formation • Type 2 DI - implicates protein specifically involved in \_\_\_\_ development > DSPP (dento-sialo-phosphoprotein) ○ Will only have a dentin defect > mimics what the patients with OI have as well ○ Only a \_\_\_\_ disease
osteogenesis imperfecta
COL1A1
DSPP
mineralization
clinically disruption bone dentin dental
Dentinogenesis imperfecta Type I
• 90% of patients with mutations in type I collagen genes – COL1A1 and COL1A2
• Other implicated genes also regulate ____ collagen biosynthesis
Each helix normally composed of 2 ____ and 1 ____
____ is main organic component of dentin
type I
COL1A1
COL1A2
collagen
Dentinogenesis imperfecta Type I
- ____ colored teeth
- ____ pulps
- Sometimes see ____ pulps
- ____ and ____ appear the same way with dental phenotypes
- Grey-amber > difficult to differentiae from AI; the distinction is made ____ not clinically
grey-amber obliterated enlarged Type I II radiographically
• Do not see pulps in this radiograph - ____ in DI (either type I or II)
○ Do see in the molars, but do not see the chambers
○ Not ____
obliterated pulps
pathognomonic
• Enamel is strikingly different from dentin - can see the ____ (unlike AI where it’s not as prominent)
distinction
Dentin dysplasia • Type 1 – Defect in \_\_\_\_ dentin – “\_\_\_\_ teeth” – \_\_\_\_ teeth severely affected – Pulps \_\_\_\_ – Prone to \_\_\_\_
• Another genetic disease ○ Type I - characterized by defect in radicular dentin - the dentin that is found within the \_\_\_\_ structure (not \_\_\_\_ dentin!) § Root dentin is produced differently than coronal ○ \_\_\_\_ is also implicated (that gives rise to DI also) § Genotype-phenotype correlation - depending on which part of \_\_\_\_ it's occurring in will determine whether DI II or DD I ○ Pulps are also obliterated (common to DI and DD) ○ Rootless > fall out \_\_\_\_ at an early age
radicular rootless deciduous obliterated infection
root coronal DSPP protein spontaneously
Dentin dysplasia
• No chambers, and the ____ are almost completely absent
○ Seen in ____, but they’re stunted (shorter than normal)
roots
molars
Dentin dysplasia
• Type2
– Defect in ____ dentin
– ____ mutations
• Type II is probably just \_\_\_\_ • Type I DD is a different disease phenotypically • How to treat > teeth are not stable > exfoliate \_\_\_\_ (mostly \_\_\_\_ upon meeting patients) ○ Teeth extracted > can be treated long term with implant therapy bc the \_\_\_\_ is unaffected
coronal DSPP spontaneously mobile bone
Hypophosphatasia • Disorder of \_\_\_\_ and \_\_\_\_metabolism • Mutations in \_\_\_\_ gene – Reduced activity of \_\_\_\_ • \_\_\_\_ defect • \_\_\_\_ defect
• Highly ____ clinical presentation – Mild to lethal
• ALPL gene > TNSALP > upon mutation, reduced activity ○ Converts pyrophosphate to inorganic \_\_\_\_ > used by HA with calcium to mineralize • Can have severe to non-severe phenotypes ○ Least severe: only have a \_\_\_\_ defect, with minimal bone complications ○ Most severe: patients born with disease and die in \_\_\_\_/shortly after birth
bone mineral ALPL non-specific form of alkaline phosphatase (TNSALP) quantitative qualitative
variable
phosphate
dental
utero
Alkaline phosphatase
• Ratio of phosphate to pyrophosphate is critical
– Phosphate needed for ____ crystals
– Pyrophosphate inhibits ____ formation
• Hydroxyapatite
– Deposited along ____ fibrils
– Contained within matrix ____
hydroxyapatite
hydroxyapatite
collagen
vesicles
Dental phenotype • \_\_\_\_ pulp chambers and canals • Absent / insufficient \_\_\_\_ – Teeth exfoliate \_\_\_\_ • All clinical forms associated with \_\_\_\_ loss of deciduous teeth
• Crowns look normal, but patients come in with \_\_\_\_ (not \_\_\_\_!) ○ Fell out over time > due to inadequate cementum lining the roots § Sharpey's fibers embed into bone and cementum, and if no cementum, then the teeth are floating without an \_\_\_\_ • Can be diagnosed \_\_\_\_ ○ Pulp is enlarged
enlarged
cementum
spontaneously
deciduous
hypodontia
genetic
anchor
radiographically
