• Affects immune response to infection
• Hyperkeratosis (palms, feet, knees, elbows)
• Periodontitis/Periodontoclasia
• Floating Teeth

What are some manifestations of Cherubism?

• Cherub-like face (all four quadrants)
• Most common appearance is bilaterally on the Mandible
• Eyes turned upward
• Widening of alveolar ridges
• Expansion of the Mandible
• Randomly distributed teeth
• Similar to Giant Cell Carcinoma in appearance

Autosomal Dominant

Sporadic

Cbfa1/Runx2 gene

(protein essential for osteoblastic differentiation and skeletal morphogenesis)

• Clavicle and Skull bone defects
• Short stature with large head
• Delayed closure of skull sutures
• Narrow, high-arched palate
• Possible cleft palate
• Numerous unerupted teeth
• Supernumerary teeth
• Prolonged retention of primary teeth
• Unerupted Permanent teeth lack cementum

FGFR2

(fibroblast growth factor receptor 2)

(involved in important processes such as cell division, regulation of cell growth and maturation, formation of blood vessels, wound healing, and embryonic development)

When growth factors attach to the FGFR2 protein, the receptor triggers a cascade of chemical reactions inside the cell that instruct the cell to undergo certain changes, such as maturing to take on specialized functions.

The FGFR2 protein plays an important role in bone growth, particularly during embryonic development. For example, this protein signals certain immature cells in the developing embryo to become bone cells in the head, hands, and feet.

• Premature closure of skull sutures (craniosynostosis)
• Broad skull (Brachyocephaly)
• Ocular Proptosis: blindness
• Hearing deficit
• Headaches
• NORMAL intelligence
• Underdeveloped Maxilla (teeth crowded)
• Midface hypoplasia
• Bifid Uvula
• "Beaten Metal" skull in radiographs

Autosomal Dominant

(same as Crouzon Syndrome)

FGFR2

(Same as Crouzon Syndrome)

What are some manifestations of Aperts Syndrome?

• Acrobrachycephaly (Tower skull)
• Ocular Proptosis
• "Beaten Metal" Radiographs of skull
• Vision loss
• Midface hypoplasia
• V-shaped arch
• "open-mouth" feature
• SYNDACTYLY of 2nd, 3rd, and 4th digits
• MENTAL RETARDATION
• Pseudo cleft-palate
• Bifid Uvula
• Crowding of Mx teeth

Both Syndromes have the same gene mutation in FGFR2

BUT...

Aperts Syndrome results in

1. SYNDACTYLY of 2nd, 3rd, 4th digits
2. MENTAL RETARDATION

 Crouzon Syndrome DOES NOT

What is the inheritence pattern of Treacher-Collins Syndrome/Mandibulofacial Dysostosis?

Autosomal Dominant

60% New Mutations

What gene is affected in Treacher-Collins Syndrome?

TCOF1 gene

Defects of the 1st and 2nd Branchial Arches

• Hypoplastic zygoma
• Narrow face, depressed cheeks
• Downward slandting palpebral fissures
• Coloboma (notch) at outer lower eyelid
• Ear tags
• Ossicle Defects
• Underdeveloped Mandible
• Cleft Palate

Autosomal Dominant

with High Penetrance

• Multiple BCCAs
• Odontogenic kertaocysts
• Palmar/Plantar pits
• Calcified falx cerebri
• Bifid ribs
• Hypertelorism

Autosomal Dominant

with 50% new mutations

The most common type is NF1 and has a mutation on

CHROMOSOME 17

2 or more of the following:

• 6 or more Cafe au lait macules (over 5 mm in prepubertal and over 15 mm in postpubertal)
• 2 or more Neurofibromas OR 1 Plexiform Neurofibroma
• Axillary Freckles (Crowe's Sign)
• Optic glioma
• Lisch Nodules (freckles on the iris)
• Distinct osseous lesions (thinning of the long bone cortex, e.g.)
• 1st degree relative with 2+ findings above

Oral Manifestations include oral lesions such as Neurofibromas; enlargement of fungiform papillae, Mandibular foramen, or mandibular canal

Autosomal Dominant

with 50% new mutations

Ret Proto-Oncogene

on CHROMOSOME 10

Marfanoid Phenotype

Narrow face, thick lips, everted upper eyelid

Neuromas on conjunctiva, eyelid margin, or cornea

Oral Lesions may be first sign

Mucosal Neuromas, bilateral commissure neuromas

Other 

Pheochromocytoma (secretion of catecholamines)

Medullary carcinoma of the thyroid

Calcitonin Production

Highly Metastatic 

What is the inheritence pattern of Peutz-Jeghers Syndrome?

Multiple Perioral and Oral Ephelides of Melanotic Macules

Intestinal Polyposis (Jejunum)

Inadequate deposition of organic matrix

NORMAL mineralization

Radiographic Contrast

7 different types

Pinpoint/head pits in rows or columns

In between normal enamel

Across the surface (buccal more severe)

Does NOT correlate with a pattern of environmental damage

Thin, hard, glossy

open bite

opaque white to brown

x-ray: peripheral thin enamel outline

unerupted teeth exhibit resorption

Defect in maturation of enamel crystals

NORMAL shape

mottled appearance

white, yellow, or brown

Enamel is soft

Radiodensity is similar to dentin

Mottled brown

chipping from dentin

Very common Anterior Open Bite

Soft, similar to hypocalcified

Calculus

Autosomal Dominant

Possibly X-linked, to?

A zone of white opaque enamel on the incisal and occlusal portions

Looks like fluorosis

Anteriors, anteriors/bicuspids, premolars/molars

BOTH dentitions

What is the inheritence pattern of Amelogenesis Imperfecta of the Hypocalcified type?

NO significant mineralization

NORMALLY shaped teeth AT ERUPTION

Enamel is very thin and is easily lost

Yellow/Brown in color

Calculus

Open Bite

Autosomal Dominant

Autosomal Recessive

and Sporadic

Type I: Most common, mildest form

Type II: Most Severe, die before 4 weeks of age

Type III: Most severe beyond perinatal stage

Type IV: Mild to moderate form

Most common type of inherited bone disease

Weak bones, altered teeth

Blue Sclera

Hearing Loss

Joint hyperextension

Premature pulpal Obliteration

Shell Teeth

Opalescent Teeth

Maxillary hypoplasia

Perinatal: Most severe

Infantile: normal up until 6 months, failure to grow afterwards

Childhood: detected later, tooth defects with enlarged pulp chambers

Adult: mild

Decreased alkaline phosphatase (enzyme important for mineralization)

Bone defects similar to rickets

Premature loss of primary teeth WITHOUT evidence of an inflammatory response

NO cementum on the teeth

PHEX gene mutation

(phosphate regulating endopeptidase homolog)

Males are more severly affected

Hypophosphatemia due to increased capacity to reabsorb phosphate

Teeth with alrge pulp chambers and pulp horns that often extend to the DEJ

Multiple Periapical Lesions

Exfoliation WITH inflammatory response

Inflammatory response

Occurs in Vit. D-Resistant Rickets but

NOT in Hypophosphatasia

(Hypophosphatasia due to lack of cementum; VitD-resistant rickets due to pinpoint exposure of pulp and inflammatory response to it)