DISEASES OF BONE

1
Bone– dynamic, mineralised, vital tissue

Continuous resorption and formation throughout life

2
Bones of maxillofacial complex
--- maxilla and mandible (unique)
--- relationship with teeth and presence of microbes in
moist oral environment ( vulnerable in infections)
---subjected to continuous stresses and strain
e.g mastication

3
Jaw Bones can be affected by
-- developmental
-- infectious
-- inflammatory
-- genetic
and neoplastic processes
Disease – can involve single or entire bony skeleton

4
Osteochondrodysplasias--- abnormalities of growth
and development of cartilage and bone (generalized
disorder of skeletal system )

Dysostoses--- malformation of individual bones single

or in combination

5
Clinical evaluation--- complete medical history
-- family history
-- physical evaluation

Radiographic evaluation – full set of skeletal

radiographs

6
OSTEOGENESIS IMPERFECTA

7
 Introduction
Osteogenesis imperfecta -- heterogeneous group of genetic diseases

Characterized by impairment of collagen maturation

 Most commonly manifests as fragility of bones

Predominantly AD mode of inheritance (occasionally Aror sporadic )

8
In 1835 Lobstein described the disease

Other names : Brittle bone disease ,

Fragilitas Ossium ,
Lobsteins disease ,
Osteopsathyrosis

9
 EPIDEMIOLOGY

Affects 1:8000 individuals

Many being still born or dying shortly

after birth

10
 Etio -pathogenesis
Abnormal type I collagen

Type I collagen fibers are found in bones, fascia, sclera,

dentin and skin ( hence disease results in defects of
these tissues )

Mutation in COL1A1 (chromosome 17q21)and COL1A2

(7q22.1)
Qualitative defects (abnormal collagen I molecule) and
quantitative defects (decrease in production of normal
collagen I molecules)
11
Basic defect in organic matrix
Fetal collagen fail Mature collagen

Osteopenia
(tendency for fracture and defective healing)

12
Some evidence -- progressive intermolecular cross-
linkage of adjacent collagen molecules,is defective in
this disease

Defective microvascular system and decreased

collagen fibril diameter have also been observed

13
 Clinical Features

Age of onset of symptoms -- varies

( often leads to stillborn or affected baby dies shortly
after birth)

Severity of C/F -- ranges from no C/F to prenatally

lethal skeletal abnormalities

14
Chief clinical characteristic --- extreme fragility and
porosity of bones (attendant proneness to fracture)

Fractures heal readily-- but new bone

is of a similar imperfect quality

Common for fractures to occur -- while an infant is

simply crawling or walking

Many times, the fractures heal by exuberant callus

formation
15
Second characteristic C/F -- occurrence of
pale blue sclera

Sclerae are abnormally thin (pigmented choroid shows

through and produces bluish colour)

Also seen in other diseases such as osteopetrosis,

foetal rickets, Turner syndrome, Paget's disease,
Marfan syndrome, and Ehlers-Danlos syndrome and
occasionally, in normal infants

16
Other features
-- hearing loss or hypoacusis (due to osteosclerosis
leading to compression of nerves)

--laxity of ligaments leading to hypermobility of joints

-- 0ccasionally, patients may have a tendency towards

capillary bleeding

17
Dental alterations that have C/F and R/F identical to
dentinogenesis imperfecta (DI)are occasionally noted

Both dentitions are involved and demonstrate blue to

brown translucence

R/F --typically reveal premature pulpal obliteration,

although shell teeth rarely may be seen

18
Altered teeth closely resemble DI , but two diseases
are result of different mutations and should be
considered as separate processes.

Such dental defects in association with systemic bone

disease should be termed OPALESCENT TEETH

19
20
21
 Classification
Silence classification (1979)
Four well-documented types (Type I to Type IV)
recognized based on clinical and genetic findings

Recently, Type V, Type VI, and Type VII were added to

the existing types

22
 Type I
Fracture Occur during infancy

 most common and mildest form

Around 10% of patients show prenatal fractures

Incidence of fractures considerably reduces -- when

patient attains puberty

AD , and joint hypermobility seen

24
Opalescent dentin may or may not be present where
features such as
blue sclera,
mild-to-moderate bone fragility,
kyphoscoliosis,
hearing loss, and
bruising tendency are consistent features

25
 Type II
Most severe form , AD/AR

Extreme bone fragility and frequent fractures.

Around 90% of the cases are either stillborn or die

before 4 weeks of postnatal life.

Prenatal fractures are common in most of the patients

26
Joint hypermobility seen and patients have severely
short stature

Blue sclera may be seen

27
 Type III
AD/AR

Associated with opalescent dentin

Sclera of variable hue,

limb shortening and
progressive deformities,
triangular facies with frontal bossing, and
pulmonary hypertension.

28
In utero fractures occur in 50% patients

Rest of the cases acquire fractures in neonatal period

No hearing loss reported

Joint hypermobility seen

29
 TYPE IV
Further subdivided into

Subtype A--- which is not associated with opalescent

dentin and

Subtype B-- which is associated with opalescent dentin

30
 Features include
-- normal sclera,
-- normal hearing,
--- fractures that begin in infancy (in utero fractures are
rare) and
-- mild angulation, and shortening of long bones. –
--- Bleeding diathesis has not been reported

31
 ORAL MANIFESTATIONS
 Class III malocclusions --- large head size, frontal
and temporal bossing, and exaggerated occiput create
a greater percentage of class III malocclusions.

Anterior and posterior cross bites and open bites are

also frequent

These conditions are seemed to be caused by maxillary

hypoplasia rather than mandibular hyperplasia
32
Opalescent dentin

Large number of impactions and ectopic teeth have

been reported

In permanent dentition, patients often have unerupted

first and second molars (rare in general population)

33
 Radiographic features
Osteopenia, bowing and angulation or deformity of
long bones, multiple fractures, and wormian bones in
skull

Wormian bones are multiple small sutural bones found
in skull which fail to fuse

34
Rarely multiple radiolucencies, radio-opacities or mixed
radiolucencies of jaw bones are noted in panoramic
radiographs.

Periapical radiographs may reveal premature pulpal

obliteration of affected teeth

35
 Histopathology
Bones exhibit thin cortices, sometimes being composed
of immature spongy bone, while the trabeculae of
cancellous bone are delicate and often show
microfractures

 Osteoblas­tic activity appears retarded and imperfect,

and for this reason thickness of long bones is deficient

Basic defect appears to lie in the organic matrix,

Calcification proceeds normally

36
t

Thin trabeculae and basophilic woven bone

37
 Treatment
No known treatment, Management of the fractures
may be a major problem

Genetic counselling

Prenatal ultrasonography –for diagnosis of prenatal

fractures

38
Prenatal diagnosis may be confirmed by performing a
chorion villus biopsy and, either by
--demonstrating production of abnormal collagen Type I
by culturing the chorion cilli cells
--or by obtaining DNA for molecular analysis of genes
involved

39
Prognosis varies from relatively good to very poor

Some patients have little to no disability, whereas others

have severe crippling as a result of the fractures.

 In severe forms death occurs in utero, during delivery or

early in childhood

40
OSTEOPETROSIS

41
Marble bone disease

Albers-Schönberg disease,

Osteosclerosis fragilis generalisata

42
INTRODUCTION
Osteopetrosis – group of rare hereditary bone disease

Primary defect –
Failure of osteoclastic bone resorption

increased bone mass with poor mechanical properties

German radiologist, AlbersSchönberg, first described in

1904
43
Etiology
Primary underlying defect -- failure of the osteoclasts to
resorb bone

Results in thickened sclerotic bones

Increased bone fragility results from

-- failure of collagen fibers to augment bone matrix and ---
from defective remodeling of woven bone to compact
bone

Specific genetic mutations seen in 70% of cases

44
Classification
Based on age and clinical features
--- Adult onset,
----Infantile, and
----Intermediate

45
C/F
Adult onset– AD

Infantile, and Intermediate– AR

Rarely few – X linked inheritance

46
Infant osteopetrosis
Infantile osteopetrosis (also called malignant
osteopetrosis) is diagnosed early in life

Many patients fail to survive or show evidence of

severe growth retardation

Mostly –widespread sclerosis and tendency to

fracture

47
Nasal stuffiness –due to mastoid and paranasal sinus
malformation presenting feature

Macrocephaly , frontal bossing, hypertelorism ,and a

short nose

Cranial nerve compression – results in sleep apnea,

blindness (due to retinal degeneration) , deafness and
facial paralysis

48
49
Deficiency of bone marrow tissue –severe anemia and
pancytopenia

Hepatosplenomegaly– compensatory extramedullary

hematopoiesis

Thrombocytopenia --- tendency for easy bruising and

bleeding
Granulocytopenia --- recurrent infection

50
Oral manifestation
Failure/ delay in eruption of teeth

Osteomyelitis – restricted blood supply especially when

patients undergo extraction

Fracture of jaw bones – even to normal extraction forces

Few case – enamel hypoplasia, microdentinal defects ,

and arrested root development seen

51
52
Intermediate osteoporosis
Becomes evident at end of first decade

Less severe variant compared to infantile

osteopetrosis

53
Adult osteopetrosis
Also called benign osteopetrosis

Diagnosed in late childhood or adult

50% patients asymptomatic

54
Diagnosis – based on family history / radiographs

Symptoms if present – mild and limited

Such patients– bone pain primary complaint

Bone marrow function not affected

55
Bone sclerosis usually restricted to axial skeleton and
increase risk to fracture

Bony defects –Scoliosis , Hip osteoarthritis

Osteomyelitis of mandible in 10% of patients –

complication of tooth extraction or dental caries

56
R/F
Usually diagnostic

Patients usually have generalized osteosclerosis

involving axial skeleton and long bones

Skull(especially base ) may be thickened and

dense

57
58
Sclerosis may be uniform or in the form of
alternating radiopaque radiolucent bands, noted
at the ends of long bones
Alternating focal sclerosis of skull base, pelvis and
vertebral end plates – Sandwich vertebrae or
Rugger jersey spine
Thickening and defective remodelling may result
in – funnel like appearance of long bones
(Erlenmayer flask deformity) and bone in
bone appearance of vertebrae and phalanges

59
60
61
Laboratory Findings
Raised levels of creatinine kinase (CK-BB) and TRAP
due to increased release from defective osteoclasts

Hypocalcemia can occur and cause rickets if it is

severe

Parathyroid hormone (PTH) is often elevated

(secondary hyperparathyroidism)

62
Histologic features
Bone biopsy not necessary usually radiographs
diagnostic
Endosteal production of bone with concomitant
lack of physiologic bone resorption
Osteoblasts seen in plenty but osteoclasts
are either seldom found ( osteoclast poor )
in plenty but functionally defective (osteoclast rich)

63
Lack of resoption –persistence of cartilage cores
in bones formed by endochondral ossification

Residual fibrous tissue may be noticed between

disorderly arranged bony trabeculae

64
65
Treatment
Infantile osteopetrosis – if untreated results in
death by first decade due to severe anemia
bleeding and/ or infection.
Primary treatment -- aimed at improving
haematopoiesis and minimizing the neu­rologic
complications ( may require haematopoitic stem
cell transplanta­tion before the age of 3 months)
 Calcitriol helps in stimulating bone resorption by
activating osteoclasts.

66
Erythropoietin and corticosteroids used to
counter anemia and stimulate bone resorption

Adult osteopetrosis generally require no

treatment and have good long term survival rates

67
 Cherubism
Familial Fibrous Dysplasia of Jaws
Multilocular cystic disease of jaws
 Introduction
First reported by Jones in 1933

Genetic disease affecting the jaw bones of children

Term "Cherubism" --- because of facial similarity of

affected children to plump cheeked angel "Cherubs"
as depicted in Baroque paintings of Ruben.
 Etiology
•AD , Mutation of SH3BP2 gene on chromosome 4p16.3
• Overactive Protein encoded by mutated gene disrupts
critical signalling pathways in cells associated with
maintenance of bone and some immunologic effecter
cells
•Leads to inflammation of jaw bones, triggering
production of osteoclasts, leading to breakage of bone
during remodeling
 C/F
•Disease of children
•Usually affected children are normal at birth (disease
starts manifesting at age of 14 months to 3 years )
•Painless, bilateral symmetrical enlargement of maxilla,
and mandible.
•Usually, earlier the lesion appears, more rapidly it
progresses
• "Cherubicface" charac­terized
by upward gaze, expansion of
both maxilla and mandible, and
cervical lymphadenopathy (full
moon face)

• rim of sclera may be visible

beneath iris because of
expansion involving orbital rim,
giving the classic "eye to
• Grotesque expansion of maxilla may at times
lead to respiratory obstruction and impair­ment of
vision and hearing.

• Mandible-- posterior body and the coronoid

process are involved, sparing the condyles.

• There is hyperplasia of the cervical lymph nodes

• Disease is self-limiting and enlargement slows
down when child reaches 5 years of age and
stops completely at 12-15 years.

• At puberty -- lesions begin to regress

spontaneously by continuous bone remodelling
• End of third decade of life, jaw bones are either
clinically normal or with minimum residual
deformity
 Oral Manifestations
• Narrowing of the maxillary alveolar ridges result

in V-shaped palate.

• Dental anomalies such as miss­ing teeth,

especially 2nd and 3rd molars, crowding, mal­

occlusion,

• Premature loss of deciduous teeth, and delayed

eruption of permanent teeth may be noticed e

Cherubism may be part of the manifestations in

• --Noonan syndrome,

• -- Ramon syndrome,

• --and Type 1 Neurofi­bromatosis

• Noonan syndrome include--- short stature,

cherubic fades, congenital heart defect, chest

defor­mity, and mental retardation.

• Ramon syndrome is associ­ated with

cherubism, mental retardation, epilepsy,

gingival fibromatosis, hypertrichosis, and

rheumatoid arthritis.
 Grading System(Arnott 1978)
• Grade I = Involvement of both mandibular

ascending rami

• Grade II = Involvement of both maxillary

tuberosities as well as mandibular ascending rami

• Grade III = McCune Albright syndrome

involvement of the whole maxilla and mandible

except coronoid process and condyles

 Radiographic Features
• bilateral, symmetrical occurence of multilocular R/L
with expansion of both jaws.
• soft tissue density in posterior-inferior part of
maxillary antrum with forward
displacement/absence of tooth follicles ----
prominence in posterior part of hard palate known
as "hard palate sign".
 Radiographic Features
• Dental anomalies such as absence of teeth, eruption
failure, or displacement along with alveolar bone de­
struction may be seen.
• Such multiple unerupted teeth with destruction of
alveolar bone --- typical Floating tooth syndrome"
appearance
• Later, when the disease is seen at the resolu­tion
phase, irregular patchy scleroses appear in radio-
lucencies imparting "ground glass" appearance
 Histologic Features
•Vascular connective tissue
with numerous large, spindle
fibroblasts, and multinucleated
giant cells

Numerous blood capillaries

lined by large endothelial cells
seen often
 
Surrounded by thick,
eosinophilic perivascular
cuffing, a feature characteristic
of cherubism.
 Treatment
•No treatment is indicated except observation.

•Rarely surgery may be considered for cosmetic

reasons and correct residual jaw deformities after
puberty
Paget's Disease

87
Introduction
Chronic, progressive disease of bone

British surgeon Sir James Paget in 1877 first described it

as "Osteitis Deformans”

Common skeletal disorder of middle-aged and elderly

patients

Involves multiple bones (polyostotic) or rarely single

bone (monostotic)

88
Pathophysiology
Characterized by abnormal and excessive
remodelling of bone

Initially increased osteoclastic activity followed

by accelerated but abnormal bone formation and
increased vascularity of bone

Bones become enlarged, weakened, and deformed

with associated complications.

89
Primarily a disease of osteoclast

Osteoblasts are morphologically normal and

consid­ered compensatory to bone resorption,

Aetiology still unknown

90
1.Genetic link
[ family history , AD and Paget's susceptibility genes
(PDB1-PDB7) spanning over chromo­somes 2, 5, 6,10,
and 18]

2. Viral etiology
(identi­fication of nuclear inclusion bodies in osteoclasts
that resembled viral nucleocapsids of paramyxovirus,
especially canine distemper virus and measles virus)

3. Others -- inflammation, autoimmune, connec­tive

tissue, and vascular disorder.

91
C/F
 Usually seen after 50 years (incidence increase
with age, rarely occurs below 20 years)

Men = women

Marked geographic predilection

(common in England, France, and Germany but
rare in certain other European countries, Africa,
and the Middle and Far East)
92
Usually as­ymptomatic

Some patients show symptoms such as bone pain,

bone deformity, neurologic, musculoskeletal, and
cardiovascular anomalies

Predilec­tion for axial skeleton

Commonly involves pelvis, femur, spine, skull
and tibia, and to a lesser extent clavicles, upper
extremities, ribs, and scapula
93
Bone pain -- most common presenting complaint
, pain may worsen at night.

Most of the affected bones show expansion and

deformity(there may be enlargement of skull and
frontal bossing )

Involvement of weight bearing bones often leads to

bowing deformity resulting in simian (monkey like)
stance
94
Long bones such as femur and tibia may be
bowed because of the lack of rigidity to support
body weight

96
Spine involvement, especially, the lumbar and
sacral region may be involved.

Softened bone at base of the skull may lead to

platybasia, the descent of the cranium onto the
cervical spine.

Skin over the affected bone may feel warm because

of the increased blood supply.

97
Facial bones involvement may cause secondary
complications including head ache, paraesthesia,
cranial nerve deficits, hearing loss, optic nerve
atrophy and blindness, neuralgias, and facial palsv.

Rarely, patients with Paget's disease may have cardio­

vascular anomalies such as aortic stenosis,
calcification of cardiac valves and conduction
abnormalities, leading to high output cardiac failure

98
Oral Manifestations
Both jaw bones are commonly involved
( slightly higher incidence in maxilla)

Progressive en­largement of the jaws, widening of

the alveolar ridge and flattening of the palate

Teeth may migrate resulting in excessive spacing

between teeth.

99
Denture wear­ing edentulous patients often
complain about tightening of dentures because of
expanding alveolar ridge

As the disease progresses -- mouth may remain

open, exposing the teeth, because lips are too
small to cover the enlarged jaw

101
R/F
3 phases
early lesions predominated by bone resorption
(osteoclastic phase

phase of resorption, and new bone formation

occurring simultaneously (mixed phase) and

finally more of bone formation (osteoblastic phase)

102
Early lytic phase--
Destructive radiolucent
areas are seen as single,
multiple or diffuse in
radiographs of affected
bones
Isolated lesion in the
skull, when large, is
sometimes referred to as
osteoporosis
circumscripta

103
mixed osteoclastic-osteoblastic phase – may show
patchy mixed radiolucency.

osteoblastic areas,-- which appeal as opacities in

radiograph tend to be patchy in distri button, eventually
becoming confluent, but often still showing minute areas
of variation in radiodensitv. termed "cotton-wool"
appearance ( well demonstrated in skull and jaws)

104
105
Jaw radiographs often exhibit loss of lamina dura and
generalized hypercementosis of teeth

Rarely, root resorption has been reported

Usually bilateral -- may show radiographic evidence

of only unilateral involve­ment of the jaw, especially
early in the course of the disease

106
107
Laboratory Findings
Total and bone-specific serum alkaline phosphatase
(BSAP) levels are usually elevated
Serum calcium and phosphorus levels are within
normal limits
Urinary hydroxyproline level is also elevated because of
the increased osteoclastic activity and bone resorption.
Recently, urinary excretion of bone specific pyridinium
collagen cross links, N-terminal telopeptide (NTX) and
alpha collagen C-telopeptide (CTX) has been found to
be sensitive and specific markers of bone resorption

108
H/P
Initial osteolytic phase -- extensive resorption of bone
and increase in the number of osteoclasts, seen as
multinucleated giant cells
Osteoclasts are abnormally large when compared to
the normal osteoclasts and contain as many as 100
nuclei.
osteoblastic phase -- small, irregular, fragments of
newly formed woven bone which often appear to be
united in a characteristic "Jig­saw puzzle" or "mosaic"
pattern
109
Repeated bono resorp­tion and subsequent bone
formation results in deeply haematoxyphilic reversal
lines in the bone
 Later osteoblastic stage, the bony islands are usually
compact and the marrow space is filled with highly
vascularized fibrous tissue. (may not show the usual
Haversian system )
Eventu­ally, the osteoblastic activity diminishes and
an osteopo­rotic or burned-out phase predominates.

110
111
Treatment and Prognosis
No specific treatment exists
 Aspirin, acetamin­ophen or other nonsteroidal anti-
inflammatory drugs are used to alleviate the bone
pain and degenerative joint dis­ease.
Most potent bisphosphonates have been widely used
since these drugs adhere to the mineralized surfaces
and inhibit osteoclastic bone resorp­tion.
Calcitonin, the parathormone antagonist, has been
used to inhibit the osteoclastic activity
NEU­ROLOGIC and cardiovascular anomalies require
evaluation and appropriate treatment plan.

113
Complications
stress fracture and secondary sarcomas.

Fractur occur most commonly in the femur followed

by oth stress-bearing bones such as tibia, humerus,
spine, and pelvis

Osteosarcomas and, to a lesser extent, chondrosarcor

and fibrosarcomas are the most serious complications
Prognosis of polyostotic less favourable than
monostotic

114
 Infantile cortical hyperostosis
(Caffey’s disease,Caffey-
Silverman syndrome)

115
 Introduction

 First reported by Roske in 1930.

 Caffey and Silverman reviewed and
coined the term in 1945.
 Infants with unusual cortical thickenings in
certain bones
 Self limited disease with unknown Etiology.
117
 ETIOLOGY
 Genetically transmitted with unknown etiology

 Theories
infectious agent with a long latency period.

defect in arterial system and

allergic reaction.
 Early Stage: Inflammation of periosteum &
adjacent soft tissue
Resolving lesion : Periosteum remains thickened
and subperiosteal immature lamellar bone
persist.
Mature lesions : thick mature lamellar bone without
inflammation or subperiosteal changes.
 CLINICAL FEATURES
 Affects both the sex equally.
 Primary manifestation as disease of triad
a) Irritability
b) Swelling of soft tissue
c) And associated bones
 On the basis of onset and presentation it has two
forms:

FAMILIAL SPORADIC FORM

FORM
Onset --At an avg. Age At an avg. Age 9 to
6 to 8week 11
May present at birth week
Tibia is usually Not present at birth
Involved
Mandible is usually
AD- mutation in
involved
COL1A1 gene
Swelling appears suddenly, which is deep, and
tender
Babies may resist to eat due to mandibular
Involvement.
Other bones which commonly demonstrate
hyperostosis are the calvarium, scapula, ribs and
tubular bones of the extremities, including the
metatarsals
Other features include fever , pseudoparalysis,
dysphagia, pleural effusion, and torticollis
Fig- Swelling in forearm
 Oral manifestation
 Residual deformity of mandible (Angle & ramus)
 Malocclusion may be seen

Fig- Pt. showing facial asymmetry

 RADIOLOGICAL FEATURES
 periosteal new bone formation
(can be florid and compact causing pronounced cortical
thickening )
 Distributed multifocal and asymmetrical
Mandible is almost invariably involved and
other commonly affected areas include the
clavicles, ribs and long bones of the limbs.
Typically, periosteal new bone or periosteal
‘cloaking’ is confined to diaphyses of the long
bones, sparing the metaphyses and epiphyses.
 HISTOLOGICAL FINDINGS
 Early stage - inflammation of periosteum and
adjacent soft tissues is observed
 As lesion begin to resolve --- periosteum
remains thickened and subperiosteal immature
lamellar bone is observed ,Bone marrow
spaces contain vascular fibrous tissue
 Mature lesions - hyperplasia of lamellar
cortical bone without inflammation or
subperiosteal changes
HISTOLOGICAL FINDINGS

Fig- bone histo slide shows Caffey's disease

 LAB FINDINGS
 ESR↑
 Serum Alkaline phosphatase↑
 Leukocytosis
 Thrombocytosis
 Anemia
 Immunoglobin level↑
 Lab tests not specific
 TREATMENT
No specific treatment
Disease ultimately resolves without sequelae
in six to nine months.
Some periods of exacerbations and remissions
may occur during the course.
Corticosteroid may be helpful to alleviate
symptoms and NSAIDS to reduce inflammation
 Marfan syndrome
(Marfan-Achard Syndrome, Arachnodactyly)

131
Heritable, genetic disorder

AD inheritance

 Famous instance
Abraham Lincoln
(not proved)
132
Etiology
Mutation in FBN1 (fibrillin 1)gene on
chromosome 15, bands q15–q23

causes defective or reduction in microfibrils

which is an essential component of elastic fibres
and other tissues of extra cellular matrix

133
Excess Transforming growth factor beta (TGF-β)
is activated

elasticity in many tissues is decreased, leading to

overgrowth and instability of tissues

134
Myriad of distinct clinical problems --
musculoskeletal,
cardiac, and
ocular problems

135
C/F
M=F

Incidence --- 1 in 5,000 to 1 in 10,000 births

including stillborn

Musculoskeletal features --shape of skull and

face is characteristically long and narrow

136
Skeleton shows overgrowth --- resulting in
disproportionately long limbs compared to trunk
(dolichostenomelia)

And joint laxity --- leading to hyper-extensibility of

joints with habitual dis­locations

Others --- Arachnodactyly and thoracolumbar

scoliosis

137
138
Cardiovascular defects
-- dilatation of aorta with a predisposition to rupture
-- mitral and tricuspid valve prolapses
-- and enlargement of proximal pulmonary artery

Ocular findings--- myopia, cataract, glaucoma,

retinal detachment, and superior disloca­tion of
lens.

139
Table 1 Revised Ghent criteria for Marfan syndrome
diagnosis
In the absence of family history of MFS
1. Aortic dilatation* (Z-score $2) AND ectopia lentis = MFS
2. Aortic dilatation* (Z-score $2) AND FBN1 mutation** = MFS
3. Aortic dilatation* (Z-score $2) AND systemic score $7 points = MFS§
4. Ectopia lentis AND FBN1 mutation with known aortic dilatation^ = MFS

In the presence of family history of MFS

1. Ectopia lentis AND family history of MFS = MFS
2. Systemic score $7 points (Table 3) AND family history of MFS = MFS§

3. Aortic dilatation* (Z-score $2 for patients .20 years of age, $3 for those
younger than 20 years) + family history of MFS = MFS§

140
Intraoral
High arched palate – consistent finding

Bifid uvula and severe malocclusion involving both

jaws

Multiple odontogenic cysts of the maxilla and

mandible occasionally reported

Rarely TMJ dysarthrosis

141
142
Radiographic Features
Skull radiographs (AP and lateral) may
demonstrate a
--- high arched palate,
-- increased skull height, and
-- an enlarged frontal sinus

143
Treatment and Prognosis
Multidiciplinary approach involving cardiologist,
orthopaedist,opthalmologist, psychiatrist ,

Genetic counselling if family history

Palatal expansion and orthodontic correction for

high arched palate and malocclusion

144
Craniosynostosis –refers to group of diseases where
there is premature fusion of one or more cranial
sutures, often resulting in an abnormal head shape

Primary (defect in ossification)or secondary (failure

of brain growth)

Sporadic or hereditary

146
Simple (one suture fuses prematurely) or compound
(premature fusion of multiple sutures )

Syndromic—complex craniosynostosis with

extracranial malformations

147
 Overview
 Most common craniofacial disease
 Rare disease
 Diagnosed at birth or early
childhood

Octave Crouzon
(1874-1938)
 Overview
 Traid of cranial deformities , facial
anamolies and exophthalmia
 Named after Octave Crouzon,
a French Neurologist who first
described this disorder in 1912.
Octave Crouzon
(1874-1938)
ETIOLOGY
 Genetic disease ,Autosomal dominant
 Gene mutation in gene coding for Fibroblast
Growth Factor Receptor II , located on
chromosome 10
leads to defective mesenchyme and ectoderm
 Hereditary or sporadic
 C/F
 M=F
 Defects noticeable at first year of age or at birth
 Different shapes of head seen are brachycephaly
( broad and short) scaphocephaly (boat shaped),
trigonocephaly (triangular) and deformity is
severe cloverleaf shaped head
 Coronal and sagittal sutures are commonly
affected sutures and fontanels are not obliterated
 Wide face with high forehead

 Maxillary hypoplasia producing pseudomandibular

prognathism

 Deviation of nasal septum and narrowed or

obliterated anterior nares result in parrot beak
appearance
 Orbits are shallow resulting in ocular proptosis

 Other ocular anomalies include hypertelorism,

strabismus and reduced monocular visual activity

 Anti-mongoloid eyelids along with other facial

features impart “frog face appearance ”
Increase in intracranial pressure may cause mild
mental retardation

Along with visual and hearing impairment , headache

and convulsions

154
 Oral manifestations
 Crowding of teeth
 Ectopic eruption of maxillary first molars
 Anterior open bite
 V shaped palatal vault with lateral palatal
swellings
 Dysphagia
Complications
 Obliteration of sutures
 Prominent cranial markings seen as depressions of
inner surface of cranial vault (beaten metal
appearance)
 Bifid spinous process
Treatment
 multidisciplinary approach
 Surgical relase of synostosis And
cranial decompression
 Later cosmetic corrections of various
facial deformities and dental
rehabilitation
158
self-healing histiocytosis, pure cutaneous histiocytosis,
Langerhans cell granulomatosis, type II histiocytosis
and non-lipid reticuloendotheliosis
INTRODUCTION

• Disease primarily affects bones, ocassionally may

affect other systems also

• group of idiopathic disorder characterized by

clonal proliferation of specialized bone marrow-
derived, antigen presenting dendritic cells called
Langerhans cells (LCs) and mature eosinophils
Langerhans cells (LCs)

•dendritic cells seen in epithelium ,lymph nodes and

bone marrow

•[presence of HX bodies or Birbeck granules (rod-

shaped with characteristic periodicity and some
times a dilated terminal end called tennis racket
appearance, intracellular in location, identified by
electron microscopy) and the presence of CD1a
antigen on the cell surface and HLA-DR positivity
confirms the Langerhans cell origin of this disease ]
• Clinical Spectrum includes 3 diseases

• Lettere-Siwe Disease: Acute fulminant and

Disseminated disease
• Hand-Schuller-Christian Disease:
Intermediate form
• Eosinophilic Granuloma: few indolent and
chronic lesions of bone and other organs
• M>F

• Disease of childhood

• Many cases progress eventually into adult life

 Pathogenesis
Still enigmatic
• Environmental

• Infectious (HHV-6 virus)

• Immunologic

• Genetic

• Probably Neoplastic
(abnormally produce at least 10 different cytokines which
are of T-cell origin and may explain recruitment of
LCs, other inflammatory cells, over expression of
adhesion molecules,fibrosis, bone resorbtion, and
necrosis)
Eosinophilic Granuloma
(Unifocal Eosinophilic
Granuloma)

165
 Eosinophilic Granuloma

• Term was intro­duced by Lichtenstein and Jaff in 1940

• Lesion of bone which is Primarily histiocytic

proliferation with an abundance of Eosinophils

(but no intracellular lipid accumulation)

• May be polyostotic or monostotic
• asymptomatic and May ne detected during routine x-
ray examination
• or the pt might complain of local pain, swelling and
tenderness
• Skull & Mandible are common sites of involvement

• Lesion may occur in the jaw and overlying soft tissues

of the mouth (similar to dento-alveolar infections)
168
• General malaise and fever occasionally accompany

• lesions are destructive and are well demarcated,

roughly round or oval in shape.

• Area destroyed is replaced by a soft tissue

• Tissue of the early lesion is soft and brown and,

since there is no necrosis, is not friable.

• Later the lesion becomes fibrous

• Radiographic Features: irregular ” radiolucencies of
bone
• H/P: Sheets of histiocytes (large pale staining
mononuclear cells ) with large no of focal collections
of eosinophils in early lesions (lesion matures,
fibrosis occurs)
Treatment and Prognosis

Prognosis in the majority of cases is excellent,

Curettage and/or X-ray therapy are curative,

Symptoms usually subsiding within two weeks after

treatment.

172
Hand-Schüller-
Christian Disease
(Multifocal eosinophilic
granuloma)
173
widespread skeletal and extraskeletal (soft tissues)
lesions and a chronic clinical course
C/F
characterized by classic triad of
•single or multiple areas of ‘punched out’ bone
destruction in skull,
•unilateral or bilateral exophthalmos,
•and diabetes insipidus with or without other
manifestations of dyspituitarism such as polyuria,
dwarfism, or infantilism
(complete triad occurs in only about 25% of patients)
Involvement of the facial bones, which is frequently
associated with soft-tissue swelling and tenderness,
causes facial asymmetry.

Otitis media is also common.

Any of the visceral organs also may be involved,

and the skin sometimes exhibits papular or nodular
lesions
Oral manifestations
• Often nonspecific and include sore mouths, with
or without ulcerative lesions; halitosis gingivitis and
suppuration; and unpleasant taste;

•loose and sore teeth with precocious exfoliation of

teeth; and failure of healing of tooth sockets
following extraction

•Loss of supporting alveolar bone mimicking

advanced periodontal disease is characteristic,
R/F
individual lesions, particularly in the skull, are
usually sharply outlined, although the lesions in the
jaws may be more diffuse

H/F, manifesting in four stages

• proliferative histiocytic phase with accumulation
of collections of eosinophilic leukocytes scattered
throughout the sheets of histiocytes
•A vascular-granulomatous phase with persistence of
histiocytes and eosinophils, sometimes with
aggregation of lipidladen (cholesterol) macrophages.

•A diffuse xanthomatous phase with abundance of

these ‘foam cells’.

•A fibrous or healing phase

 Laboratory Features
•Anemia and, less frequently, leukopenia, and
thrombocytopenia are occasionally found
• serum cholesterol level is nearly always normal,
(tissue cholesterol content may be elevated
remarkably)
Treatment
• prognosis is good.
• Approx half of the patients undergo spontaneous
remission over a period of years
• treatment of choice is curettage or excision of
lesions.
•Inaccessible lesions may be irradiated.
•Some patients benefit from chemotherapeutic
drugs, including prednisone, vinblastine, and
cyclophosphamide.
LETTERER
SIWE DISEASE

181
•

•Acute fulminating disorder

•Occurs in infants below 3 years

C/F
• initial manifestation is often a skin rash involving
the trunk, scalp, and extremities.

•This rash may be erythematous, purpuric, or

ecchymotic, sometimes with ulceration.
•
•patients will also commonly have a persistent, low-
grade spiking fever with malaise and irritability.
•. Splenomegaly, hepatomegaly, and lymphade-
nopathy are early manifestations

•as well as nodular or diffuse involvement of visceral

organs, particularly the lungs and gastrointestinal
tract, later in the course of the disease.

•Diffuse involvement of the skeletal system also

usually occurs later in the disease
. Oral Manifestations

•The oral lesions may consist of ulcerative lesions,

•Further­more, diffuse destruction of bone of maxilla

and man­dible may occur, causing loosening and
premature loss of teeth.
Histologic Features
•basically a histiocytic proliferation with or with­out
eosinophils.
• these histiocytes do not con­tain significant
amounts of cholesterol so that foam cells are not a
feature of the disease, nor fibrosis is encoun­tered
.
Laboratory Features
Progressive anaemia is often present as well as
leukop nia or thrombocytopenia
Treatment and Prognosis

•prognosis in Letterer-Siwe disease is extremely

poor

• In the majority of cases, the course of the disease

is rapid and terminates fatally in a short time.
•
•However, some patients show response to
chemotherapy and are some times maintained in
remission for years
APERT SYNDROME
(Acrocephalosyndactyly)

188
named after French physician Eugene Apert
(described it in 1906)
rare AD disorder
characterized by
craniosynostosis,
craniofacial anomalies, and
syndactyly (cutaneous and bony fusion) of hands and feet

189
Etiology
Mutation in fibroblast growth factor receptor 2
(FGFR2) (maps to chromosome bands 10q25–q26)

increase in no of precursor cells that enter osteogenic

pathway.

Increased subperiosteal bone matrix formation and

premature calvaria ossification during fetal
development

190
C/F
M=F

1 in 65000 live births

 highest prevalence in Asians

191
C/F
Acro/Brachycephaly (when coronal suture affected )

Prominent forehead and flat occiput

Ears low with occasional conductive hearing loss

192
C/F
 Eyes exhibit down-slanting palpebral fissures,
hypertelorism, shallow orbits, proptosis and
exophthalmos

Nose has a markedly depressed nasal bridge.

And is short and wide with a bulbous tip, parrot-

beaked appearance,

193
194
C/F
 Syndactyly involves the hands and feet with partial-
tocomplete fusion of the digits, often involving second,
third, and fourth digits with common nail
 often are termed mitten hands and sock feet

 Intelligence varies from normal to subnormal

mentality.

Hyperhidrosis is commonly seen

195
C/F
Cardiovascular manifestations like atrial septal defect,
patent ductus arteriosus, ventricular septal defect and
pulmonary stenosis are present.

Gastrointestinal, genitourinary and respiratory

symptoms may be present in a small percentage of
cases

196
O/M
jaw shows a prominent mandible, maxillar y
hypoplasia(mid facies deficiency)
drooping angles of the mouth,hypotonic lips
high arched V-shaped palate, bifid uvula,cleft palate,
crowded upper teeth,
 malocclusion, delayed and ectopic eruption, shovel-
shaped incisors, supernumerary teeth,

197
Treatment
Multidisciplinary approach with surgical care( brain
decompression)

Orthognathic surgery to correct dental abnormalities

198
Cleidocranial Dysplasia
(Marie and Sainton’s disease,Scheuthauer-Marie-
Sainton syndrome, mutational dysostosis)

199
Introduction
Hereditary disorder of bone , AD

Diverse group of features including characteristic

hypoplasia or agenesis of clavicle ,delayed ossification of
fontanels in skull , abnormalities of cranial bones and
narrow thorax

Bossing of frontal, parietal, and occipital regions give

the skull a large globular shape with small face.
sometimes referred to as the Arnold head

200
Etiology
Mutations in the core-binding factor alpha-1
(CBFA1) gene, located on chromosome 6p21
(plays major role in formation of osteoblasts and
differentiation of chondrocytes)

 Arrests both endochondral and membranous bone

formations

 Failure of cartilage to mature into bone

202
 Clinical features
Skull Anomalies: Brachy cephalic head ( Wide & Short)
Large Open fontanels or delayed closing of fontanels

Mostly Open sutures & wormian bones if sutures close

Sunken sagittal suture giving the skull a flat appearance

Underdeveloped paranasal air sinuses

Clavicular disturbance:

Complete absence of clavicles , sometimes partial absence

Leading to unusual mobility of shoulders which can be

brought forward till they meet at midline

 Oral Manifestations
High, Narrow arched palate with ocasional cleft palate

Hypoplastic maxilla

Prolonged retention of Deciduous teeth and

subsequent delay in eruption of permanent teeth
Roots are short and thin and may be deformed

Absence of Cellular cementum in teeth

Numerous unerupted supernumerary teeth

 Radiographic Features
Wide anterior fontanels & sutures with wormian bones

in skull
Absence of clavicles or reduced to fragments

Marked delay in ossification of pelvic bones

Numerous unerupted supernumerary teeth in

radiograph
Crypt formation around impacted teeth & ectopic teeth
Treatment
No specific treatment
Oral rehabilitation important

209
DOWN SYNDROME
trisomy 21 syndrome,
mongolism, congenital
acromicria syndrome
Genetic disease primarily manifests as form of
mental retardation with characteristic morphologic
features
(mongolism)

Characteristic clinical presentation first described by

John Langdon Down in 1866
Three cytogenetic variants cause Down syndrome:
Trisomy 21 (47 chromosomes ; 95% cases)
Chromosomal Translocation (extra chromosome material of
21 chromosome is translocated to another chromosome)
Mosaicism (denotes the presence of two or more
populations of cells with different genotypes in an individual
who has developed from a single fertilized egg)

Children with the translocation type are more

commonly born to mothers above 30yrs of age
 Clinical features
Incidence is 1 in 700 births (most common cause of mental

retardation in preschool children)

Characteristic features of Mongolism can be recognized at

birth
Mental retardation with an IQ of 25-50

Head appearance: Small head (brachycephaly)

 Hypertelorism

 Depressed nasal bridge

 Flat occiput and broad short neck

Ocular anomalies:
 Narrow, Upward and outward slanting of palpebral fissures

 Strabismus (Squint) and retinal detachment

Small and misshapen ears with anomalies of the folds are
observed
Skeletal anomalies :
 Short stature with broad and short hands, feet & digits

 Clinodactyly of fifth finger and wide gap between 1st and 2nd toes

 Muscle hypotonia and decreased response to normal stimuli

Protuberant abdomen

Hypogenitalism,, delayed incomplete puberty

Congenital defects of heart

Rarely Recurrent respiratory infections leukaemia,

epilepsy, and presenile dementia

 Oral Manifestations
Small mouth (because of hypoplasia of maxilla) with

protrusion of tongue (macroglossia)

Difficulty in eating and speaking,

Scrotal tongue & Geographic tongue

Fissuring and thickening of lips

Angular chelitis
Delayed tooth eruption ,Partial anodontia ,Enamel
hypoplasia
Ocassionally Cleft lip & Palate and Juvenile periodontitis

TREATMENT
No specific therapy exists
About 25–30% of patients die during the first year of life.
most frequent causes of death are respiratory infections
(bronchopneumonia) and congenital heart disease
Tricho-dento-osseous Syndrome
Tricho-dento-osseous Syndrome
Hereditary condition which chiefly involves the hair,
teeth, and bones.
AD mutation in DLX gene

Individuals have full head of kinky(thick curly) hair,

which sometimes tends to straighten with age.
Nails are thin and likely to peel or fracture.
chief bony abnormality is bones which are found to be
more dense than normal
.
ENAMEL hypoplasia ,yellow-brown discoloration of
teeth

Defective enamel may cause Teeth to become infected

and dental abscesses are common during the first few
years of life

 On dental X-ray, large pulp chambers (taurodontia) are

found
Chondro-Ectodermal Dysplasia (Ellis-
Van Creveld Syndrome)

223
characterized by four components,
chondrodysplasia,
Poly­dactyly,
ectodermal dysplasia affecting the hair, teeth, and
nails,
and congenital heart failure

224
Oral Manifestations
 fusion of the middle portion of the upper lip to the
maxillary gingival margin eliminating the normal
mucolabial sulcus.
 middle portion of the upper lip appears hypoplastic.
Natal teeth, prematurely erupted deciduous teeth, fre­
quently occur as well as congenital absence of teeth,
particu­larly in the anterior mandibular segment.
Tooth eruption is often delayed and those erupted are
commonly defective, being small, cone-shaped,
irregularly spaced and demon­strating enamel hypoplasia.

225
Achondrogenesis
Charecterised by defective endochondral
ossification ,large skull with prominent abdomen and
anasarca
Classified into Type I and Type II
Life threatening disease most affected infants are still
born or fail to survive
Dwarfism short limb and trunk , narrow thorax with
,large skull with prominent abdomen
O/M -- retrognathia and double chin

226
Achondroplasia
Considered most common cause of dwarfism
Disturbance of endochondral bone formation due to
FGFR3 gene mutation
C/F –abnormally short stature large head with frontal
bossing, hypoplasia of mid – face short limbs for long
trunk(limitation of joint motion but may have
unusual strength)
O/M –maxillary hypoplasia and malocclusion

227
Thank you.

228
Achondro
Autosomal dominant inherited non-lethal form of

Chondrodysplasia
Etiology: mutation of FGFR-3 on chromosome 4

Mutations leading to Cartilagenous anomalies:

 Endochondral ossification
 Proliferation of chondrocytes in growth-plate cartilage
 Cellular hypertrophy
 Cartilage matrix
 Clinical features
Characterized by :
Short Stature (dwarf) - Midfacial hypoplasia
Frontal bossing - Thoracolumbar protruberance
Disproportionately long trunk with short limbs

Limitation of joint motion

Achondroplastic dwarf has disproportionate size of head when

compared to body
Normal intelligence & unusual strength
 Oral Manifestations
Maxillary hypoplasia and hence leading to relative

mandibular prognathism and malocclusion

Sometimes congenitally missing teeth and disturbance

in shape of teeth can be seen

 Radiographic Features
Midface hypoplasia, frontal prominence

Reduced foramen magnum

Shortening of long bones and mild clubbing at ends

Premature fusion of the bones of the base of skull

1. Developmental Disturbance of TMJ
1. Hypoplasia or Aplasia of Condyle
1. Congenital or Primary Hypoplasia or Aplasia
2. Acquired or Secondary Hypoplasia or Aplasia
2. Condylar Hyperplasia
3. Bifid Condyle

2. Traumatic Disturbances of TMJ

1. Dislocation of the Condyle
2. Ankylosis
3. Injuries of Articular Disk : Internal Derangement
4. Condylar Fracture
3. Inflammatory Disturbance of TMJ
1. Osteoarthritis (Degenerative Joint Disease)
2. Rheumatoid Arthritis
3. Septic Arthritis (Infectious)

4. Neoplastic Disturbance of TMJ

1. Benign & Malignant Tumors of Bone
2. Belign & Malignant Tumors of Cartilage
 Etiology
Mechanical theory
Mandibular hypoplasia occurs btw 7th and 11th week of
gestation

Leads to tongue being high in oral cavity, causing cleft

in palate by preventing closure of palatal shelves

Leads to glossoptosis and obstruction of airway passage

 Etiology
• Neurological Maturation Theory: Delay in
neurological maturation of the tongue musculature, the
pharyngeal pillars and the palate as well as delay in
hypoglossal nerve conduction leads to the development
of Pierre robin sequence
• The spontaneous correction of majority of cases with
age supports this theory
• Rhombencephalic Dysneurulation Theory: The
motor and regulatory organization of the
rhombencephalus is related to a major problem of
 Clinical Features
• Micrognathia of mandible, it has a small body,
obtuse gonial angle and a posteriorly located condyle
• The mandibular hypoplasia resolves usually by 5 – 6
yrs
• Glossoptosis is seen, which along with mandibular
hypoplasia can cause severe respiratory and feeding
difficulty in the newborn
• Obstructive sleep apnea may occur

• Cleft palate may occur, which can affect the soft and
hard palate and is usually U-shaped or V-shaped
• Other anomalies are seen which include:
• Otitis media and hearing loss
• Nasal deformities
• Dental and philtral malformations

• Anomalies involving the musculoskeletal system

such as Syndactyly, dysplastic phalanges, polydactyly,
clinodactyly, hyperextensible joints ,etc
• CNS disturbances such as language delay, epilepsy,
neurodevelopmental delay, hypotonia, etc
• Consists of 3 essential components

• Micrognathia or Retrognathia

• Cleft Palate

• Glossoptosis, often accompanied by airway

obstruction (Tongue is not large but because of small

mandible, the tongue falls back on the airway and

causes obstruction)
247