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Inherited Oral DiseasesInherited Oral DiseasesDisorders Affecting Periodontium/Gingiva• Papillon-LeFèvre Syndrome• Cyclic Neutropenia

Disorders affecting Jaw bones and Facies

• Cherubism• Cleidocranial dysplasia• Gardner syndrome• Mandibulofacial dysostosis

(Treacher-Collins syndrome)• Nevoid basal cell carcinoma

syndrome• Osteogenesis Imperfecta• Aperts Syndrome• Crouzon Syndrome

Disorders affecting Oral Mucosa• Hereditary Hemorrhagic Telangiectasia• Multiple Endocrine Neoplasia

Syndrome IIB• Neurofibromatosis• Peutz-Jeghers Syndrome• White Sponge Nevus

Disorders of Teeth• Amelogenesis Imperfecta• Dentinogenesis Imperfecta• Dentin Dysplasia• Hypohidrotic ectodermal dysplasia• Hypophophatasia• Vitamin D deficient rickets

Papillon-LeFèvre Syndrome

• Autosomal Recessive• Cathepsin C gene mutation which affects the immune

response to infection

• Hyperkeratosis of the palms and feet• Sometimes elbows and knees• Dramatic periodontitis (periodontoclasia) of both

dentitions – Floating teeth– DD: Langerhans’ cell disease

Teeth erupt in normal sequence, position and time

1.5 to 2 years, a severe gingivo-periodontal inflammatory process develops

Edema, bleeding, alveolar bone resorption, and mobility of teeth withconsequent exfoliation

Teeth are lost in the sequence they are erupted. After loss of last teeth,gingiva regains a normal appearance

Permanent teeth are lost before 14 years

Peripheral blood neutrophil is depressed in all patients with Papillon-Lefèvresuggesting that neutrophils are important factor in pathogenesis of severeperiodontal disease

Papillon-LeFèvre Syndrome

Retinoid therapy: Improves the skin condition but not the periodontal therapy

Periodontal condition: No effective treatment

Treatment

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Cherubism

• Autosomal dominant• Facial appearance similar to “cherub”-like• 2 – 5 yrs of age• The clinical alterations typically progress until puberty,

stabilize and slowly regress• Bilateral involvement of the posterior mandible – most

common appearance – “cherub”-like (all 4 quadrants)• “Eyes upturned to heaven” appearance – due to involvement

of the infraorbital rim and orbital floor• Painless bilateral expansion of the post. mand.• Marked widening and distortion of alveolar ridges• Tooth displacement and eruption failure

Radiographic features• Multilocular radiolucency with massive expansion• Both erupted and unerupted teeth are randomly distributed• After stabilization, lesions exhibit a “ground glass” appearanceHistopathology• Similar to giant cell granuloma• But clinical and radiographic correlation necessary• Vascular fibrous tissue and giant cells (smaller and

more focal)• Eosinophilic cuffing around blood vesselsTreatment• Prognosis is unpredictable• Delayed till after puberty (curettage)

Cherubism

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CleidocranialCleidocranial DysplasiaDysplasia

Caused by a defect in Cbfa1/Runx2 geneCaused by a defect in Cbfa1/Runx2 gene

Autosomal dominant and sporadic patternAutosomal dominant and sporadic pattern

Bone defects involve the clavicle and skullBone defects involve the clavicle and skullClavicles are absent (unilateral or bilateral) Clavicles are absent (unilateral or bilateral) –– 10% of cases10% of cases

Short stature with large heads; ocular Short stature with large heads; ocular hypertelorismhypertelorism; broad; broadbase of nose and depressed nasal bridgebase of nose and depressed nasal bridge

Large heads and parietal bossingLarge heads and parietal bossing

Skull sutures show delayed closure and may remain openSkull sutures show delayed closure and may remain open

Dental manifestations include narrow, highDental manifestations include narrow, high--arched palatearched palatewith increased prevalence of cleft palate with increased prevalence of cleft palate

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Presence of numerous unerupted permanent andPresence of numerous unerupted permanent andsupernumery teeth with many distorted crown and root shapessupernumery teeth with many distorted crown and root shapes

Prolonged retention of deciduous teeth and delay or completeProlonged retention of deciduous teeth and delay or completefailure of eruption of permanent teethfailure of eruption of permanent teeth

Histology:Histology:Unerupted permanent teeth lack secondary cementum Unerupted permanent teeth lack secondary cementum

Treatment:Treatment:No treatment; fullNo treatment; full--mouth extractions with denture construction;mouth extractions with denture construction;removal of primary and supernumery teeth followed byremoval of primary and supernumery teeth followed byexposure and orthodontic treatment of permanent teethexposure and orthodontic treatment of permanent teeth

CleidocranialCleidocranial DysplasiaDysplasia

CrouzonCrouzon Syndrome (Craniofacial Syndrome (Craniofacial DysostosisDysostosis))

CraniosynostosisCraniosynostosis: Premature closure of sutures: Premature closure of sutures

Mutation in FGFR2; 1 in 65,000 births; ADMutation in FGFR2; 1 in 65,000 births; AD

Wide variation in clinical presentation: Wide variation in clinical presentation: BrachycephalyBrachycephaly;;scaphocephalyscaphocephaly; ; trigonocephalytrigonocephaly; ; ““cloverleafcloverleaf”” skull (skull (kleeblattschkleeblattschäädeldel))

Ocular Ocular proptosisproptosis: blindness and hearing deficit: blindness and hearing deficit

Headaches; normal intelligenceHeadaches; normal intelligence

Underdeveloped maxilla: Underdeveloped maxilla: MidfaceMidface hypoplasia; crowding ofhypoplasia; crowding ofmaxillary teeth; bifid uvulamaxillary teeth; bifid uvula

““Beaten metalBeaten metal”” skull in radiographsskull in radiographs

Surgical treatmentSurgical treatment

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ApertsAperts Syndrome (Syndrome (AcrocephalosyndactylyAcrocephalosyndactyly))

CraniosynostosisCraniosynostosis syndromesyndrome

Mutation in FGFR2; 1 in 65,000 to 160,000 births, ADMutation in FGFR2; 1 in 65,000 to 160,000 births, AD

AcrobrachycephalyAcrobrachycephaly (tower skull); (tower skull); kleeblattschkleeblattschäädeldel (severe cases)(severe cases)

Ocular Ocular proptosisproptosis; ; hypertelorismhypertelorism; vision loss; ; vision loss; ““beaten metalbeaten metal””radiographsradiographs

MidfaceMidface hypoplasia; hypoplasia; ‘‘VV””--shaped arch shaped arch ““openopen--mouthmouth”” feature;feature;hearing losshearing loss

SYNDACTYLY of the 2SYNDACTYLY of the 2ndnd, 3, 3rdrd and 4and 4thth digits; MENTAL RETARDATIONdigits; MENTAL RETARDATION

Pseudo cleft palate due to swellings (accumulation of Pseudo cleft palate due to swellings (accumulation of glycosglycos--aminoglycansaminoglycans) of the lateral hard palate and crowding of) of the lateral hard palate and crowding ofmaxillary teeth; bifid uvulamaxillary teeth; bifid uvula

Surgery Surgery

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TreacherTreacher--Collins Syndrome (Collins Syndrome (MandibulofacialMandibulofacial DysostosisDysostosis))

Defects of 1Defects of 1stst and 2and 2ndnd BABA

AD; 1 in 25,000 to 50,000 births; 60% new mutationsAD; 1 in 25,000 to 50,000 births; 60% new mutations

Mutations in the TCOF1 geneMutations in the TCOF1 gene

Characteristic face: Characteristic face: HypoplasticHypoplastic zygomazygoma causing narrow face withcausing narrow face withdepressed cheeks and downward slanting depressed cheeks and downward slanting palpebralpalpebral fissuresfissures

ColobomaColoboma (notch) at the outer portion of lower eyelid(notch) at the outer portion of lower eyelid

Ears anomalies: Deformed Ears anomalies: Deformed pinnaepinnae, extra ear tags, middle ear, extra ear tags, middle earossicle defects cause hearing lossossicle defects cause hearing loss

Underdeveloped mandible; Underdeveloped mandible; condylecondyle and and coronoidcoronoid hypoplasiahypoplasia

Lateral facial Lateral facial cleftingclefting and cleft palateand cleft palate

No treatment required in most cases; Cosmetic surgery inNo treatment required in most cases; Cosmetic surgery insevere casessevere cases

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Multiple Nevoid Basal Cell Carcinoma Syndrome (Gorlin

Syndrome)• A.D.; high penetrance, variable expressivity• patched mutation, chr. 9• Chief characteristics: multiple basal cell

carcinomas, odontogenic keratocysts, epidermal cysts, palmar/plantar pits, calcified falx cerebri, rib anomalies, hypertelorism

• Less common: strabismus, kyphoscoliosis, CNS tumors

Multiple Nevoid Basal Cell Carcinoma Syndrome (Gorlin

Syndrome)• Face: Frontal and temporoparietal bossing

(big head), hypertelorism, mild mandibular prognathism

• Skin: Basal cell carcinomas even in children and adolescence, often on non-sun exposed skin, few to hundreds; plantar and palmarpits (retardation of the epithelial growth)

• Skeletal: bifid ribs, kyphoscoliosis• More than one odontogenic keratocysts

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Neurofibromatosis(von Recklinghausen disease of

the skin)

• A.D.; 50% of cases are new mutations; 1:3,000 births

• Many forms• NF1 most common; chr. 17• Malignant transformation

Neurofibromatosis(von Recklinghausen disease of the skin)

• Diagnostic criteria (2 or more needed)– Six or more café au lait macules over 5mm in

prepubertal and 15mm in postpubertal– Two NFs or one plexiform NF– Axillary freckles (Crowe’s sign)– Optic glioma– Lisch nodules (brown pigmented spots of the iris)– Distinct osseous lesions (thinning of long bone cortex)– 1st degree relative with 2 or more of these findings

Neurofibromatosis(von Recklinghausen disease of

the skin)

• Oral lesions– NFs anywhere– Enlargement of fungiform papillae– Enlargement of mandibular foramen– Enlargement of the mandibular canal

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Multiple Endocrine Neoplasia, Type IIB

• MEN I: tumors of pancreatic islets, adrenal cortex, parathyroid glands and pituitary gland

• MEN IIA: Sipple syndrome, pheochromocytomas and medullary thyroid carcinoma

• MEN IIB: MEN IIA and mucosal neuromas

Multiple Endocrine Neoplasia, Type IIB

• A.D.; 50% new mutations• Mutation of ret proto-oncogene, chr.10• Marfanoid phenotype• Narrow face, thick lips, everted upper eyelid• Neuromas on conjuctiva, eyelid margin or cornea• Oral lesions may be the first sign

– Lips, anterior tongue, buccal mucosa, gingiva, palate, bilateral commissural neuromas

Multiple Endocrine Neoplasia, Type IIB

• Pheochromocytoma– Secretion of catecholamines– Sweating, diarrhea, headaches, flushing,

heart palpitations and hypertension• Medullary carcinoma of the thyroid

– Calcitonin production– Highly metastatic

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PeutzPeutz--JeghersJeghers SyndromeSyndrome

Autosomal DominantAutosomal Dominant

Multiple perioral and oral Multiple perioral and oral ephelidesephelides or or melanoticmelanotic maculesmacules

Intestinal Intestinal polyposispolyposisConsidered Considered hamartomashamartomas but have minimal neoplasticbut have minimal neoplasticpotential (2 to 3% potential (2 to 3% adenocarcinomaadenocarcinoma))Small intestine (jejunum)Small intestine (jejunum)Abdominal pain, rectal bleeding and diarrhea Abdominal pain, rectal bleeding and diarrhea

Peutz-Jeghers syndrome

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Amelogenesis Imperfecta

General Information

• Classification is impractical for clinicians• Problems arise in one or more of the

three stages of enamel formation– Elaboration of enamel matrix; hypoplastic– Mineralization; hypocalcified– Maturation; hypomaturation

General Information

• Absence of systemic disorder • Can be part of a syndrome• Many types • Different modes of inheritance• Understanding of molecular events• 1:800 – 1:15,000 (clustering)• Both dentitions

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Hypoplastic type

• Inadequate deposition of organic matrix• Normal mineralization• Radiographic contrast• Seven types

Hypoplastic typeGeneralized Pitted

• A.D.• Pinpoint/head pits in rows or columns• In-between enamel normal• Across the surface• Buccal surface more severely affected• Does not correlate with pattern of

environmental damage

Hypoplastic typeGeneralized Pitted

Hypoplastic typeGeneralized Pitted

Hypoplastic typeDiffuse Smooth A.D.

• Thin, hard, glossy• Like crown preparations, open bite• Opaque white to brown• X-ray: peripheral thin enamel outline• Unerupted exhibit resorption

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Hypoplastic typeDiffuse Smooth A.D.

Hypoplastic typeDiffuse Smooth A.D.

Hypomaturation Type

• Defect in the maturation of enamel crystals

• Normal shape• Mottled appearance• White, yellow or brown• Enamel is soft• Radiodensity similar to dentin

Hypomaturation TypeDiffuse Pigmented A.D.

• Mottled brown• Chipping from dentin with an explorer• Very uncommon anterior open bite• Soft similar to hypocalcified• Calculus

Hypomaturation TypeDiffuse Pigmented A.D.

Hypomaturation TypeDiffuse Pigmented A.D.

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Hypomaturation TypeSnow-capped Teeth

• X-linked, A.D.?• Zone of white opaque enamel on incisal and

occlusal surface (1/4 to 1/3 of the surface)• Looks like fluorosis• Anteriors, anteriors/bicuspids,

premolars/molars• Both dentitions

Hypomaturation TypeSnow-capped Teeth

Hypomaturation TypeSnow-capped Teeth Hypocalcified Type

• A.D. or A.R. (more severe)• No significant mineralization• Normally shaped teeth at eruption• Enamel very thin and easily lost• Yellow or brown color• Calculus• Open bite

Hypocalcified Type Amelogenesis ImperfectaTreatment

• Restorations as soon as possible• Dentures (overdentures)• Veneers in mild cases• Glassionomers for better adhesion to

dentin

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Osteogenesis ImperfectaOsteogenesis Imperfecta

Heterogeneous group of disorders characterized by impairmentHeterogeneous group of disorders characterized by impairmentof collagen maturationof collagen maturation

Mutations in type I collagen gene Mutations in type I collagen gene

Most common type of inherited bone diseaseMost common type of inherited bone disease

Collagen forms a major portion of bone, dentin, Collagen forms a major portion of bone, dentin, scleraesclerae,,ligaments, and skinligaments, and skin

Autosomal dominant, autosomal recessive hereditary; sporadicAutosomal dominant, autosomal recessive hereditary; sporadic

Severity variesSeverity varies

Weak bones, blue sclera, altered teeth, hearing loss,Weak bones, blue sclera, altered teeth, hearing loss,long bone and spine deformity and joint hyperextensionlong bone and spine deformity and joint hyperextension

Radiographic features include osteopenia, bowing,Radiographic features include osteopenia, bowing,deformity of long bones and multiple fracturesdeformity of long bones and multiple fractures

Oral manifestations are clinically similar to Oral manifestations are clinically similar to dentinogenesisdentinogenesisimperfecta imperfecta –– premature pulpal obliterationpremature pulpal obliteration

Shell teeth can also be notedShell teeth can also be noted

However the two are different processes caused by differentHowever the two are different processes caused by differentmutationsmutations

Opalescent teeth if associated with OIOpalescent teeth if associated with OI

Maxillary hypoplasiaMaxillary hypoplasia

Osteogenesis ImperfectaOsteogenesis Imperfecta

Four major types of OIFour major types of OI

Type I: Most common and mildest formType I: Most common and mildest formType II: Most severe; patients die before 4 weeks of ageType II: Most severe; patients die before 4 weeks of ageType III: Most severe form beyond the perinatal ageType III: Most severe form beyond the perinatal ageType IV: Mild to moderate formType IV: Mild to moderate form

Treatment:Treatment: No treatment of OINo treatment of OIVaried prognosisVaried prognosis

Osteogenesis ImperfectaOsteogenesis Imperfecta

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Shell Teeth

Hypophosphatasia

• Autosomal recessive trait• Decreased alkaline phosphatase• Increased blood and urinary phosphoethanolamine• Bone defects similar to rickets

• Premature loss of primary teeth without evidence of inflammatory response– No cementum on teeth

Perinatal: most severeInfantile: normal till 6 months; failure to grow after that (severe)Childhood: usually detected at later age; teeth defects with enlarged pulpchambers; open fontanelles with premature fusion of cranial suturesAdult: mild

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Vitamin D-Resistant Rickets(Hereditary Hypophosphatemic Rickets)

Rickets resistant to vitamin DInherited as X-linked dominant traitMales affected more severely than femalesMutations in PHEX gene

Rickets, hypophosphatemia due to decreaed capacity to reabsorb phosphate

Teeth with large pulp chambers with pulp horns that extend almostto the DE junction leading to very small pulp exposures leading to multiplePeriapical lesions and gingival sinus tracts

It will as though periapical lesions on otherwise normal teeth as theexposures are so tiny