GENETIC BONE DISEASES

PRESENTATION
LUYINDI CHARLSE
20/U/21899/PS
YEAR THREE
Osteogenesis imperfecta
Osteogenesis imperfecta is a group of genetic conditions in which the bones have reduced bone
density and fracture easily.
Pathology:
Most types of OI are inherited as an autosomal dominant trait.
The casual genes are COL1A1 and COL1A2 procollagen genes.
Procollagen fails to form a normal alpha helix, polymerize into normal type 1 collagen in the
bone matrix and collagen cannot mineralize.
Without appropriate matrix, osteoblasts are unable to form normal amounts of bone leading to
fractures.
The bones are thin and lack the usual cortex of compact bone.
pathology
Development of epiphyseal cartilages is unmpaired so that bones in most types can grow to
their normal length. But they become grossly distorted by multiple fractures and result in
dwarfism.
Approximately 60% have joint hypermobility but otherwise the majority have good health.
Sillence classification of OI
Type I: This is the most common and mildest form. It is subdivided into 1A and 1B. In subtype
1A, dentinogenesis imperfecta is absent while in subtype 1B, dentinogenesis imperfecta is
present. Symptoms in both include blue sclera, mild to moderate bone fragility with frequency
of fractures decreasing after puberty, kyphoscoliosis, hearing loss, easy bruising and short
stature.

Type II: It exhibits extreme bone fragility and frequent fractures. Blue sclera maybe present but
hearing loss is not common. Dentinogenesis imperfecta maybe present along with small nose,
micrognathia and short trunk.
Sillence classification of OI
Type III: It is associated with dentinogenesis imperfecta, sclera of variable hue, limb shortening
and progressive deformities, triangular facies with frontal bossing and pulmonary hypertension.
No hearing loss occurs.

Type IV: Subdivided into IVA and IVB. In subtype IVA, dentinogenesis imperfecta is absent while
subtype IVB, dentinogenesis imperfecta is present. Symptoms of both include normal sclera,
normal hearing, fractures that begin in infancy and mild angulation and shortening of long
bones.
Clinical features of OI
Blue sclerae
Triangular facies
Macrocephaly
Fragility and porosity of bones
Barrel chest
Scoliosis
Fractures
Joint laxity
Growth retardation
Limb deformities
Oral manifestations of OI
Class III malocclusions
Anterior and posterior cross bites and open bite.
Unerupted first and second molars
Dentinogenesis imperfecta
Large number of impactions and ectopic teeth.
Radiographic features of OI
These include osteopenia, bowing, angulation or deformity of the long bones, multiple fractures
and wormian bones (sutural bone) in the skull
Histologic findings of OI
These include thin and porous bone cortex, thin delicate widely spread trabeculae, less bone
tissue, woven or nonlamellar bone with collagen fibers of small size and random distribution,
retarted and imperfect osteoblasic activity and inter molecular cross linkage of adjacent collagen
molecules is absent.
Treatment and prognosis of OI
No known treatment
No medical therapy is involved other than the treatment of infections when they occur.
Prognosis varies from relatively good to poor.
Type IA, normal life expectancy.
Type IIB, most patients die within one year of life.
A slight decrease in life expectancy has been observed in other types.
Osteopetrosis (mable bone disease)
Osteopetrosis is a group of rare hereditary skeletal disorders characterized by a marked increase
in bone density.
Pathology:
It is due to defect in remodeling caused by failure of normal osteoclast function.
Defective osteoclastic bone resorption, combined with continued bone formation and
endochondral ossification, results in thickening of cortical bone and sclerosis of the cancellous
bone.
However, their increased size does not improve their strength. Instead, their disordered
architecture results in weak and brittle bones that results in multiple fractures with poor
healing.
Types of osteopetrosis
Infantile osteopetrosis: It is also called malignant osteopetrosis. It is diagnosed early in life.
Presenting feature is nasal stuffiness. Failure to survive and growth retardation are symptoms.
Manifestations include deafness, proptosis, hydrocephalus, osteomyelitis of the mandible,
fragile bones, anemia, sleep apnea, and blindness.

Adult osteopetrosis: It is also called benign osteopetrosis. Approximately one half of the patients
are asymptomatic and diagnosis is made incidentally or is based on family history.
Manifestations include deafness, facial palsy, osteomyelitis of the mandible, bone pain, carpal
tunnel syndrome, osteoarthritis, blindness, frontal bossing, short stature, and
hepatosplenomegaly.
Oral manifestations of osteopetrosis
Reduced medullary spaces of the jaws
Osteomyelitis of the mandible
Fracture of bone during tooth extraction
Enamel hypoplasia
Dentinal defects
Arrested root development
Radiographic features of osteopetrosis
Bones are uniformly sclerotic
Bones have a club-like appearance
Bone within bone (endo bone) appearance is seen
Vertebrae are extremely radiodense and they show alternating bands. This called rugger-jersey
sign.
Histologic features of osteopetrosis
Tortuos lamellar trabeculae replaces the cancellous portion of the bone.
Globular amorphous bone deposition in the marrow spaces.
Osteophytic bone (bone spurs) formation.
Numerous osteoclasts maybe seen but there is no evidence that they function because ship’s
lacunae are not visible.
Treatment and prognosis of
osteopetrosis
Bone marrow transplantation
Interferon gamma-1b in combination with calcitriol, has shown to reduce bone mass, decrease
the prevalence of infections and lower the frequency of nerve compression.
Administration of corticosteroids (to increase circulating RBCS and platelets), parathormone,
macrophage colony stimulating factor and erythropoietin.
Limitation of calcium intake
Prognosis can change remarkably in some patients after bone marrow transplantation. Patients
with adult osteopetrosis have good long term survival rates.
Achondroplasia
It is also known as chondrodystrophia fetalis
It is a common nonlethal form of chondrodysplasia.
It is transmitted as an autosomal dominant trait with complete penetrance.
Achondroplasia is caused by mutations in the gene for fibroblast growth factor receptor -3
(FGFR3).
The common mutations cause a gain of function of the FGFR3 gene resulting in decreased
endochondral ossification, inhibited proliferation of chondrocytes in the growth plate cartilage,
decreased cellular hypertrophy and decreased cartilage matrix production.
Clinical features of achondroplasia
Short stature
Rhizomelic shortening of the arms and legs
A disproportionately long trunk
Trident hands
Midfacial hypoplasia
Frontal bossing
Thoracolumbar protuberance
True megalocephaly
Limitation of joint motion
Oral manifestations of achondroplasia
Retruded maxilla due to the restriction of the growth of the skull base.
Class III malocclusion with mandibular prognathism
Congenitally missing teeth
Crowded teeth
Radiographic features of
achondroplasia
Lateral skull radiograph reveals,
Midfacial hypoplasia
Enlarged calvaria
Frontal prominence
Shortening of the base of the skull
Diminished foramen magnum
Premature fusion of the bones in the base of the skull.
Histological features of achondroplasia
Defective endochondral ossification
Normal intramembranous and periosteal ossification
Loss of columnation in chondrocytes
Irregular bony trabecule
Treatment and prognosis
No treatment for achondroplasia
Treat middle ear infections and dental crowding
If the patient survives the first few years of life, the chances are excellent that he/she will have
the life expectancy of a normal person.
Cleidocranial dysplasia
It is also known as Marie and sainton’s disease, scheuthanermarie-saniton syndrome, mutational
dystosis.
It is defined as a congenital disorder of bone formation manifested with clavicular hypoplasia or
agenesis with a narrow thorax, which allows approximation of the shoulders in front of the
chest.
It is manifested as retardation or partial failure of the development of the bones of the clavicle
and of the skull but not of the mandible.
Cleidocranial dysplasia is a familial congenital transmitted as autosomal dominant trait. It caused
by mutations in the core binding alpha-1 (CBFA1) gene located on chromosome 6p21.
Clinical features of cleidocranial
dysplasia
Characterized by abnormalities of the skull, teeth, jaw, shoulder girdle as well as by occasional
stunting of long bones.
Head is brachycephalic
Paranasal sinuses are underdeveloped and narrow
Faulty development of foramen magnum
Dysplasia of paranasal sinuses
Defects of vertebral column, pelvis and long bones as well as of bones of digits are also relatively
common
Oral manifestations
High narrow arched palate
Cleft palate
Underdeveloped and smaller maxilla in relation to the mandible
Prolonged retention of deciduous teeth
Delayed eruption of permanent teeth
Roots of the teeth are short and thinner than normal
Complete absence of cementum
Crown maybe pilled as a result of enamel hypoplasia
Radiographic features
Wide patent anterior fontanel and sutures with wormian bones in cranium.
Marked delay in ossification of pelvic bones.
Deficient middle third of the clavicles
Spina bifida is observed in the cervical and upper thoracic levels.
Shortened and broad carpal, metacarpal, tarsal and metatarsal bones.
Treatment
No specific treatment
Care of oral conditions is important
Retained deciduous teeth should be restored if they become carious since extraction does not
necessary induce eruption of the permanent teeth.
Cherubism
Cherubism is a rare developmental jaw condition that is generally inherited as an autosomal
dominant trait
It is a non-neoplastic hereditary bone lesion that histologically similar to central giant cell
granuloma, affects the jaws of children bilaterally and symmetrically usually producing the so
called cherubic look.
According to WHO classification, cherubism belongs to a group of non-neoplastic bone lesions
affecting only the jaws.
It caused by mutations in the SH3BP2 gene located on chromosome 4p16.3.
Pathophysiology
Mutation in SH3BP2 gene
Increased stimulation of progenitor myeloid cells to produce macrophages and osteoclasts
Increased inflammation with giant cells and Increased resorption of the jaw bones results in
swollen face especially around the jaw bones.
Clinical features of cherubism
Occurs between 2 and 5 years
Enlarged face due to swelling of the jaws
The clinical alterations typically progress until puberty then stabilize and slowly regress
The cherub like facies
“eyes upturned to heaven” appearance that is due to a wide rim of exposed sclerae noted below
the iris
Painless bilateral expansion of the posterior mandible that tends to involve the angles and
ascending rami
Oral manifestations
Agenesis of the second and third molars of the mandible
Displacement of the teeth
Premature exfoliation of primary teeth
Delayed eruption of permanent teeth
Grading system
Arnott suggested the following grading system for the lesions of cherubism;
Grade I: Involvement of both mandibular ascending rami
Grade II: Involvement of both maxillary tuberosities as well as mandibular ascending rami
Grade III: Involvement of the whole maxilla and mandible except the coronoid process and
condyles
Radiographic features
Bilateral multiocular cystic expansion of the jaws
Displacement of inferior alveolar canal
Small tightly compressed trabecular pattern producing ground glass appearance
Destruction of alveolar bone causes displacement of teeth producing floating tooth syndrome
Thinning of cortical plates
Histopathologic features
Numerous multinucleated giant cells.
Diffuse background of spindled mononuclear cells, fresh hemorrhage
Eosinophilic fibrinous material, eosinophilic cufflike deposit surrounding small blood vessels
Treatment
Surgery is not usually indicated. If necessary, surgery is usually undertaken after puberty when
the remission phase of the lesions have been reached, unless esthetic considerations or severe
functional problems justify earlier treatment.
Marfan syndrome
It is also called Marfan-Achard syndrome
Marfan syndrome is a spectrum of disorders caused by a heritable genetic defect of connective
tissue that has an autosomal dominant mode of transmission.
It is caused by a defect in gene FBN1 located on chromosome 15, bands q15-q23 which codes
for connective tissue protein, fibrillin.
Clinical features of Marfan syndrome
Archnodactyly
Dolichostenomelia (i.e. long limbs relative to trunk length)
Thoracolumbar scoliosis
Long and narrow skull
Hyper extensibility of the joints with habitual dislocations
Kyphosis
Flat feet
Aortic dilation
Aortic regurgitation
Myopia
Retinal detachment
Oral manifestations
High arched palate
Bifid uvula
Malocclusion
Multiple odontogenic cysts of the maxilla and mandible
Temporomandibular dysarthrosis
Radiographic features
High arched palate
Increased skull height
Enlarged frontal sinus
Treatment and prognosis
No specific treatment for the condition
Management of cardiovascular manifestations
Patient longevity now approaches that of persons without Marfan syndrome, although
cardiovascular compromise is still the most common cause of patient death.
References
Shafer’s text book of oral pathology, 7th edition
Cawson’s essentials of oral pathology and oral medicine, 9th edition