Metabolic and genetic disorders of bone

2. METABOLIC AND GENETIC
DISORDERS OF BONE
Presented by
Dr Ravindra Mahanthi
1st MDS
Dept of Oral Pathology & Microbiology

3. Contents:
• Introduction
• Bone
▫ Anatomy
▫ Histology
▫ Physiology
• Bone Physiology & Metabolism
• Role of bones in general metabolism
• Classification of bone disorders
• METABOLIC DISORDERS OF BONE
• GENETIC DISORDERS OF BONE
• Refferences

4. Introduction
• Bone is a highly specialized supporting framework
of the body, characterized by its rigidity,hardness,
and power of regeneration and repair.
• A disease is a pathophysiological response to
internal or external factors.
• A disorder is a disruption to regular bodily
structure and function.
• A syndrome is a collection of signs and symptoms
associated with a specific health-related cause.
• Dysostosis: Malformation of individual bones
single or in combination

5. Anatomy- Histology- Physiology

6. Bone is a mineralized connective tissue
consisting by
• 28% type I collagen and
• 5% noncollagenous matrix proteins,
such as
• Bone sialoprotein,
• osteocalcin,
• osteonectin,
• osteopontin, and
• proteoglycans
• 67% of Inorganic matrix is by hydroxyapatite
(Ca10[PO4]6[OH]2)

7. •
Appearence Bone Type Example
Gross appearance
Flat Skull, pelvis, scapula
Long Axial skeleton
Macroscopic
appearance
Compact Mature bone; flat bones and shaft of long
bones
Spongy/cancellous/
trabecular
Early embryonic bone; interior of extremities
of long bones
Development/
formation
Intramembranous Direct transformation of mesenchyme
Endochondral From a cartilage model
Regions
Diaphysis Shaft
Metaphysis Transitional portion of the shaft leading to the
growth plate zone
Epiphysis Extremities of long bones
Microstructure Embryonic/woven Irregular collagen network
Lamellar Collagen arranged in concentric layers
Disposition of
lamellae
Circumferential Found on periosteal and endosteal surfaces
Osteonic Concentric lamellae forming osteons
Interstitial Residual fragments between osteons

9. Gross Histology of Bone

10. Cells in Bone

13. Bone Metabolism
• The regulation of bone and bone mineral
metabolism results from the interactions among
three important hormones –
▫ parathyroid hormone (PTH)
▫ Calcitonin
▫ vitamin D

14. Role of Bone in General metabolism
• Mineral Reservoir:
Bones act as homeostatic reservoir of minerals
important for the body,
Eg: calcium and phosphorus.
These minerals are removed from and replaced in bone to
serve systemic homeostatic needs irrespective of loss of
skeletal structural integrity.
• Growth Factor and Cytokine Depository:
Growth factors that can be released upon bone
resorption and can exert their effects locally and
systemically.
Eg: Insulin-like growth factors (IGF), transforming
growth factor-B (TGF- B) and bone morphogenetic
proteins (BMP)

15. • Fat Repository:
The yellow bone marrow acts as a storage reserve of
fatty acids.
• Acid–base Equilibrium:
Bone buffers the blood against excessive pH changes
by absorbing or releasing alkaline salts.
• Detoxification:
Bone tissues are capable of storing heavy metals and
other elements, thus removing them from the circulation
and helping in reducing their effects on other tissues.

16. • Endocrine Function:
A hormone called osteocalcin is also released by
bone, which contributes to the regulation of
blood glucose and fat deposition.

17. Molecular-pathogenetic classification of Bone Disorders
Group-1 Defects in extracellular structural
proteins
Osteogensis Imperfecta
Achondrogenesis
Group-2 Defects in metabolic pathways Osteopetrosis
Hypophosphatasia
Group-3 Defects in folding and degradation of
macromolecules
Pyknodysostosis
Group-4 Defects in hormones and signal
transduction mechanisms
Rickets
Osteoporosis
Group-5 Defects in nuclear and transcription
factors
Cleidocranial dysplasia
Group-6 Defects in oncogenesis and tumor
suppressor genes
Cherubism
Group-7 Defects in RNA and DNA processing
and metabolism
Cartilage- hair-
hypoplasia

19. METABOLIC BONE DISEASES
• Examples of metabolic bone diseases include
▫ Osteoporosis
▫ Rickets
▫ Osteomalacia
▫ Marble bone disease (osteopetrosis)
▫ Fibrous dysplasia.
▫ Hyperparathyroidism
▫ Acromegaly

20. Osteoporosis:
• Osteoporosis means “porous bones”
• It causes bones to become weak and brittle – so
brittle that even mild stresses like bending over,
or coughing can cause a fracture.

21. • Low levels of calcium, phosphorus and other
minerals in the bones result low bone density.
• SYMPTOMS:
▫ Periodontal disease, reduced jaw bone density and
tooth loss.
▫ Back pain, which can be severe if fractured or
collapsed vertebra.
▫ Loss of height over time, with an accompanying
stooped posture.
▫ Fracture of the vertebrae, wrists, hips or other
bones.

22. • Although it's often thought of as a women's
disease, osteoporosis also affects many men.
• RISK FACTORS:
▫ Sex – Fractures from osteoporosis are about twice
more in women than in men. Risk in women at
menopause (45 yrs) that accelerates bone loss.
Risk in men is greater than age 75.
▫ Age - The older, the higher risk of osteoporosis.
Bones become weaker as ages.
▫ Race - Greatest risk – white or of Southeast Asian
descent. Black and Hispanic men and women have
a lower, but still significant risk.

23. ▫ Family history - Osteoporosis runs in families.
Parent or sibling with osteoporosis puts at greater
risk, especially if having a family history of
fractures.
▫ Frame size - Men and women who are
exceptionally thin or have small body frames tend
to have higher risk because they may have less
bone mass to draw from as they age.
▫ Lifetime exposure to estrogen-The greater a
woman's lifetime exposure to estrogen, the lower
her risk of osteoporosis.

24. ▫ Eating disorders - Women and men with anorexia
nervosa or bulimia are at higher risk of lower bone
density in their lower backs and hips.
▫ Corticosteroid medications - Long-term use like
prednisone, cortisone, prednisolone and
dexamethasone, is damaging to bone.
▫ Common treatments for chronic conditions –
asthma, rheumatoid arthritis and psoriasis.
▫ Thyroid hormone -Too much thyroid hormone can
cause bone loss.

25. ▫ Other medications-Long-term use of the blood-
thinning medication heparin, the cancer treatment
drug methotrexate, some anti-seizure
medications, diuretics and aluminum-containing
antacids also can cause bone loss.
▫ Breast cancer - Postmenopausal women who have
had breast cancer are at increased risk of
osteoporosis, especially if they were treated with
chemotherapy or aromatase inhibitors such as
anastrozole and letrozole, which suppress
estrogen

26. ▫ Low calcium intake - A lifelong lack of calcium plays a
major role in the development of osteoporosis.
▫ Sedentary lifestyle -Children who are physically active
and consume adequate amounts of calcium-containing
foods have the greatest bone density. Exercise
throughout life is important, but can increase bone
density at any age.
▫ Chronic alcoholism -For men, alcoholism is one of the
leading risk factors for osteoporosis. Excess
consumption of alcohol reduces bone formation and
interferes with the body's ability to absorb calcium.
▫ Depression -People who experience serious depression
have increased rates of bone loss.

27. • Histopathology:

28. TREATMENTS AND DRUGS:
• Hormone therapy (HT)
• Prescription medications – Bisphosphonates,
Raloxifene (Evista) / selective estrogen receptor
modulators (SERMs), Calcitonin, Teriparatide
(Forteo), Tamoxifen.
• ESTROGEN AND BONE PROTECTION
Estrogen is essential for healthy bone, and that
when the production of estrogen is reduced, as
occurs normally in postmenopausal women and
pathogenically after exposure to radiation or
chemotherapeutic drugs, bones become brittle and
break easily. However, the mechanisms involved
aren't clearly understood

29. RICKETS:
• Rickets refers to any disorder in the vitamin D-
Calcium-Phosphours axis which results in hypo
mineralized bone matrix
• Rickets is a condition that most often occurs due
to malnutrition.
• Symptoms can include weak bones and bowed
legs.
• Providing a child with extra vitamin D and some
minerals usually resolves rickets.
• Rickets can also occur as the result of a genetic
condition.

30. Etiology:
• The main cause of rickets is a lack of vitamin D.
• Not consuming enough calcium can cause
rickets, as may vomiting, diarrhea, and liver
diseases.
• Certain complications of digestive disorders can
also cause rickets.
• Low intake of vitamin D, which means that low
exposure to sunlight can also contribute.

31. Clinical features:
• bone pain
• bone tenderness
• bones break easily
• costochondral swelling, or prominent knobs on the bone
between the ribs and the breast plate.
• Harrison's groove, which is a horizontal line visible on
the chest where the diaphragm attaches to the ribs
• low levels of calcium in the blood
• knock knees in older children
• a soft skull
• short height and low weight
• possible spinal, pelvic, or cranial deformities
• bowed legs in toddlers
• uncontrolled muscle spasms that can affect the entire
body
• widening wrists

33. Oral Manifestations:
• Developmental abnormalities of Dentin and enamel like
Enamel hypoplsia
• Delayed eruption
• Misalignment of teeth in the jaws.
Treatment:
• The treatment of rickets focuses on increasing the
patient's intake of calcium, phosphates, and vitamin D.
• Harmonal therapy and Fluoride adminstration

34. OSTEOMALACIA:
• known as Adult rickets
• Only flat bones and the diaphysis of the long
bones are effected.
• Most common in Post menopasual females with
a history of low calcium intake.
Clinical Features:
Softening and distortion of the skeleton
increased tendency towards fractures.
Pelvic deformities are commonly seen.

35. Oral Manifestations:
• Severe periodontitis
Histological features:
• Attempt at bone remodeling with inadequate
calcification is seen.
• Cortical bone is thin
• Osteoid boarders are seen in trabeculae
Treatment:
• Dietary enrichment of vitamin-D and Calcium
• Harmonal therapy
• if the Osteomalacia is secondary to malabsorption then
the dialy dietary fat intake should be restricted.

36. HYPERPARATHYROIDISM:
Mainly two types:
Primary hyperparathyroidism
▫ Single adenoma-
▫ Multiple adenomas
▫ Nodular hyperplasia
▫ Carcinoma
Secondary hyperparathyroidism
▫ Chronic renal insufficiency
▫ Malabsorption
▫ Osteomalacia & rickets
• Hyperparathyroidism may result in either bone resorption or bone
formation, bone resorption usually dominates.
• Normal values are 10 to 55 pg/ml

37. Clinical Features:
Skeletal manifestations(Bones)
• Severe pain, tenderness
• General weakness
• Deformity of limbs & spine
• Pathological & delayed union
Renal manifestations: (Stones)
• Renal colic
• Polyuria, dypsia, nocturia, hypercalcemia
• Renal failure
GIT manifestations:(Abdominal groans)
• Anorexia, nausea, vomiting, constipation, dyspepsia,
peptic ulceration
Psychological manifestations(Psychic moans):
• Depression, drowsiness, impaired cognitive
function

38. Bone pathology
• Rapid progressive resorption, softening of the
bones with deformity
• Loss of phosphorus and calcium- generalized
osteoporosis.
• Formation of pseudocyst due to resorption of
newly formed bone.
• Cysts of varying size occur- thin brownish fluid
filled
• Haversian canal gets enlarged- osteoblasts -
becomes fibrous .

39. Radiological features:
• The bones of affected persons show general
radiolucency as compared with those of normal people
• Later sharply defined round or oval radiolucent areas
develop which may be lobulated
• Small cystic areas may be seen in the calvarium and
large or small sharply defined radiolucencies are seen in
maxilla and mandible
• In the jaws of the bone exhibits GROUND GLASS
APPEARANCE
• Lamina dura around the teeth may be partially lost

41. Histological features:
• osteoclastic resorption of the trabeculae of the spongiosa and
along the blood vessels in the Haversian system of the cortex.
• Fibrosis, especially of the marrow spaces, is marked
• Development of osteoclastomas characterized by masses of
fibroblasts growing in a loose syncytium, among which are
numerous capillaries and endothelium-lined blood spaces, red
blood cells, many areas of yellow or brown hemosiderin, and
innumerable multinucleated giant cells.
• Therefore, any patient who has a lesion diagnosed as a central
giant cell lesion should be evaluated medically to rule out the
possibility of hyperparathyroidism

42. ACROMEGALY:
• Chronic metabolic disorder in which there is too
much growth hormone and the body tissue
gradually enlarge.
• Acromegaly is uncommon and physical changes
occur gradually, the condition often isn't
recognized immediately: sometimes not for
years.
• If not treated promptly, acromegaly can lead to
serious illness and even become life-threatening.

43. ETiOLOGY:
• Acromegaly is caused by pituitary tumors that
secrete GH or, very rarely by extrapituitary
disorders
• Regardless of the etiology, the disease is
characterized by elevated levels of GH and IGF1
with resultant signs and symptoms of
hypersomatotropism.
• Pituitary Acromegaly -More than 95% of
patients with acromegaly will have a GH-
secreting pituitary adenoma

44. Clinical features:
• Enlarged hands and feet
• Coarsened, enlarged facial
features
• Coarse, oily, thickened skin
• Excessive sweating and body
odor
• Small outgrowths of skin
tissue (skin tags)
• Fatigue and muscle weakness
• A deepened, husky voice due
to enlarged vocal cords and
sinuses
• Severe snoring due to
obstruction of the upper
airway

45. • Impaired vision
• Headaches
• Enlarged tongue
• Pain and limited joint mobility
• Menstrual cycle irregularities in women
• Erectile dysfunction in men
• Enlarged liver, heart, kidneys, spleen and other organs
• Increased chest size (barrel chest)
Oral manifestations:
• Enlargement of mandible and maxilla
• Gaps btween teeth due to alveolar overgrowth
• Condylar hyperplasia with concomitant bone formation at the
anterior portion of mandible and distinct increase in bony angle
produce prognathism
• Thickened oral mucosa, increased salivary gland tissue,
macroglossia

46. Treatment:
The treatment of a patient with acromegal y is
typically directed at the removal of the pituitary
tumor mass and the return of the growth
hormone levels to normal.
Radiation therapy may be used in some instances ,
but the return of the growth hormone levels to
normal is not as rapid or as predictable as with
surgery.

48. GENETIC DISORDERS OF BONE
▫ Osteogenesis Imperfecta
▫ Osteopetrosis(Marble bone disorder)
▫ Achondroplasia
▫ Cleidocranial dysplasia(Dysostosis)
▫ Mandibulofacial dysostosis
▫ Cherubism
▫ Down`s syndrome

49. OSTEOGENESIS IMPERFECTA
Etiology:
• Pathologic changes seen in all tissues in which type 1
collagen is an important constituent (eg, bone, ligament,
dentin, and sclera)
• Basic defect : qualitative or quantitative reduction in
type 1 collagen
• it is caused by mutations in genes encoding type 1
collagen (COL1A1 and COL1A2)
• Mutations are either genetically inherited or new
• Inherited mutations : recurrence risk in subsequent
pregnancies of 50% if a parent is affected
• New mutations unpredictable recurrence risk

50. Clinical Features:
• Blue sclerae
• Triangular facies
• Macrocephaly
• Hearing loss
• Defective dentition
• Barrel chest
• Scoliosis
• Limb deformities
• Fractures
• Joint laxity
• Growth retardation
• Constipation and sweating

51. Sillence classification:

52. Type-1 - it is commonly known as Osteogenesis imperfecta with blue
sclera. A lower-than-normal amount of type I collagen is
present. Collagen structure is normal.
Type-2- Also called as Osteogenesis imperfecta congenita. it is a very
severe type which causes prenatal death.
Type-3- is a progressively deforming type with normal sclera. It is
characterized by structurally defective type I collagen. This
poor quality type I collagen is present in reduced amounts in
the bone matrix.
Type-4- type I collagen structurally defective. Sclera is normal. And
most of the symptoms subside after the puberty.
• This blue sclera is caused by thinness and transparency
of the collage fibers of sclera that allow visualization of
the underlying uvea.

53. Oral Manifestations:
• Class-III Malocculusion and
cross bite due to maxillary
hypoplasia
• Large number of impactions
and ectopic teeth.
• Unerupted first and second
molars
• Dentinogenesis imperfecta-
Disturbance in tooth
formation associated with
Osteogenesis imperfecta.

54. Histological Findings:
• Width of cortex, and volume of
cancellous bone decreased in all
types of OI
• Number and thickness of
trabeculae reduced
• Osteoblastic activity is retarted
and imperfect.
• Fetal collagen does not
transform in to mature collagen
• inter molecular cross linkage of
adjacent collagen molecules is
absent( maturation defect of
collagen)

55. Treatment and Prognosis:
• No known treatment.
• No medical therapy other than the treatment of
infections when they occur.
• Prognosis varies from relatively good to poor
• Type IA- Normal life expectenancy.
• Type IIA- Most patients die within one year of
life.

56. Marble bone disease (osteopetrosis)
• Osteopetrosis is a group of rare hereditary skeletal
disorders characterized by a marked increase in bone
density
• 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.

57. • 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.
• There are two separate sub types of
osteopetrosis:
▫ Infantile autosomal recessive osteopetrosis
▫ Benign adult autosomal dominant osteopetrosis

58. Autosomal recessive osteopetrosis
• Infantile autosomal recessive osteopetrosis is the more
severe form that tends to present earlier.
• Hence, it is referred to as "infantile" and "malignant“,
compared to the autosomal dominant osteopetrosis.
• By age 6, 70% of the affected will die.
• Most of the remainder have a very poor quality of life
with death resulting by the age of ≈ 10.

59. Clinical Features:
Those who survive childbirth present with :
• Cranial nerve entrapment
• Snuffling (nasal sinus architecture abnormalities)
• Hypercalcaemia
• Pancytopaenia (anaemia, leukopaenia and
thrombocytopaenia)
• Hepatosplenomegaly (extramedullary haemopoesis)
• intracerebral haemorrhage (thrombocytopaenia)
• Lymphadenopathy
• One of the commonest presentations is with ocular
disturbance: failure to establish fixation, nystagmus or
strabismus. The cause of these symptoms is compression
of the cranial nerve roots because of foraminal
overgrowth.

60. Autosomal dominant osteopetrosis :
• The autosomal dominant type is less severe than
its autosomal recessive mate.
• Hence, it is also given the name "benign" or
"adult" since patients survive into adulthood.
Clinical Features:
• 50% patients are asymptomatic
• Recurrent fractures
• Mild anemia
• Rarely cranial nerve palsy

61. Oral manifestation:
• Reduced medullary spaces of the jaws
• More prone to Osteomyelitis.
• Fracture of bone during tooth extraction
• Enamel hypoplasia
• Dentinal defects
• Arrested root development.
Radiographical Features:
• Bones are uniformly sclerotic.
• Bones appear club like
• Bone within bone (Endo bone) appearance is also seen.
• Vertebrae are extreamly radiodense and they show
alternating bands- rugger- jersey sign.

63. Histopathology:
Several patterns of abnormal
endosteal bone formation have
been described. These include
the following:
• Tortuous lamellar trabeculae
replacing the cancellous
portion of the bone
• Globular amorphous bone
deposition in the marrow
spaces
• Osteophytic bone (Bone spurs)
formation.
• Numerous osteoclasts may be
seen, but there is no evidence
that they function because How
ship 's lacunae are not visible.

64. Treatment and Prognosis:
• Bone marrow transplantation is the only hope for
permanent cure.
• Interferon gamma-l b, often in combination with
calcitriol, has been shown to reduce bone mass, decrease
the prevalence of infections, and lower the frequency of
nerve compression.
• Administration of corticosteroids (to increase circulating
red blood cells and platelets), para thormone,
macrophage colony stimulating factor, and
erythropoietin.
• Limiting calcium intake also has been suggested.
• Additional therapy consists of supportive measures.such
as transfusions and antibiotics for the complications.

65. ACHONDRGENESIS
• Heterogenous group of chondrodysplasia
• Lethal to neonates.
• Two types based on raidiographic and histological
features
▫ Type-1A
▫ Type-1B
▫ Type-2
Etiology:
•Type-1A- Autosomal recessive with an unknown
chromosomal locus.
•Type-1B- Autosomal recessive due to mutations of
DDST( diastrophic dysplasia sulfate transporter)
gene.

66. • Type-2- Autosomal dominant type
collagenopathy due to mutations in COL2A1
gene.
Clinical features:
• Males and females are affected equally.
Type-1
• Large head and soft skull
• Sloping forehead
• Convex facial plane and flat nasal bridge
• Small nose with anteverted nostrills
• Long philtrum
• Retrognathia
• Results in still birth more frequently.

67. Type-2
• Large head
• Prominent forehead
• Flat facial plane and flat nasal bridge
• Small nose with anteverted nostrills
• Normal philtrum
• Micrognathia

68. Histological features:
Type-1A
• Normal cartilage matrix
• No collagen rings around the chondrocytes
• Vacuolated chondrocytes
• intrachondrocytic inclusion bodies
• Extra skeletal cartilage involvement
• Enlarged lacunas
Type-1B
• Coarsened collagen around chondrocytes
Type-2
• Cartilage with large primitive mesenchymal
chondrocytes with abundant clear cytoplasm
• Cartilagenous matrix is deficient.

69. ACHONDRPLASIA
• Non lethal form of chondrodysplasia
• An autosomal dominant condition.
Etiology:
• It is caused by a mutation of the fibroblast
growth factor receptor-3 (FGFR3) gene on
chromosome 4.
• Studies show correlation with paternal age
(Higher risk k 35)

70. Clinical features:
• Most common form of Dwarfism .Although there are
over 200 types of dwarfism, two-thirds have
achondroplasia
• Head is large
• forehead is prominent
• Hydrocephalus (excess fluid on the brain) may present
• Midface deficiency
• Protruding lower jaw,
• Disproportionate features
• Upper extremities are shorter than lower extremities
• Hands are short; fingers are stubby
• Average adult height is about 4 feet tall

71. Normal Achondroplasia

72. Oral manifestations:
• Retruded maxilla due to the restriction of the growth of
the skull base.
• Class-iii Malocculusion with mandibular prognathism.
• poor dental structure, crowded teeth
• Congenitally missing teeth.
Radiographic features:
Lateral skull radiograph reveals
• Midfacial hypoplasia
• Enlarged calvaria
• Frontal prominence
• Shortning of the base of the sull
• Diminished foramen magnum.
• Premature fusion of the bones in the base of the skull.

74. Histological features:
• Endochondral ossification is mainly defective.
• Loss of columnation in chondrocytes.
• Loss of normal proliferation
• irregular bony trabecule is present
Treatment:
No treatment
Dental crowding should be treated

75. CLEIDOCRANIAL DYSPLASIA
• Also known as marie & sainton’s disease,scheuthaner-
marie-saniton syndrome,mutational dystosis.
• It is defined as a congenital disorder of bone formation
manifested with clavicular hypoplasia or agenesis with a
narrow thorax, with 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.

76. Etiology :
It is a
• familial
• congenital condition transmitted as autosomal
dominant trait.
• Mutations in the core binding factor alpha 1
(CBFA) gene located on chromosome 6p21 is the
cause of cleidocranial dysplasia.

77. CLINICAL FEATURES:
• Characterized by abnormalities
of 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.
• Defect of shoulder girdle ranges from absence of clavicle about
in 10% of cases, to partial absence or even thinning of one or
both clavicles.
• Defects of vertebral column, pelvis & long bones as well as of
bones of disease are also relatively common.

78. ORAL MANIFESTATIONS:
• Maxilla & paranasal sinuses are underdeveloped
resulting in maxillary macrognathia.
• Maxilla underdeveloped in relation to mandible.
• Prolonged retention of deciduous teeth and subsequent
delay in eruption of teeth.
• Complete absence of cementum.
• Disorganization of developing permanent dentition.
• Presence of supernumerary teeth usually in anterior
region.
• High narrow arched palate and cleft palate is common.
• Roots of teeth are often short and thinner than normal.
• Crown may be pilled as a result of enamel hypoplasia.

80. MANDIBULO FACIAL DYSOSTOSIS:
• Also known as Treacher Collins-Franceschetti
Syndrome.
• Involves structures derived from the 1st and 2nd
pharyngeal arch, groove and pouches.
• Autosomal dominant disorder characterized by
certain facial features including receding chin
and malformed ears

81. Etiology:
• TCS probably derives from inhibition of the
facial structures corresponding to the first and
second branchial arches.
• Autosomal dominant disorder.
• The responsible gene was first mapped to the
long arm of chromosome 5 (5q32-q33.1)

82. Clinical Features:
• Antimongoloid palpebral fissures
• deficiency of the eyelashes {and sometimes the upper
lids}.
• Hypoplasia of the facial bones especially of the malar
bones and mandible.
• Malformation of the external ear and occasionally of the
middle and internal ears.
• Macrostomia-high palate (sometimes cleft) and
abnormal position and malocclusion of the teeth.
• Blind fistulas between the angles of the ears and the
angles of the mouth.
• Atypical hair growth in the form of a tongue-shaped
process of the hairline extending towards the cheeks.
• Other anomalies such as Facial clefts and skeletal
deformities

84. RADIOGRAPHIC FEATURES:
• Downward slopping floors of
orbits
• Peaked bony nasal contours
• Aplastic in hypoplastic
zygomatic complex
• Obtuse mandibular angle
Treatment:
No treatment

85. CHERUBISM:
• Cherubism is a rare developmental jaw condition that is
generally inherited as an autosomal dominant trait.
• The name cherubism was applied to this condition
because the facial appearance is similar to that of the
plump-cheeked little angels (cherubs) depicted in
Renaissance paintings.

86. Etiology:
• it is generally inherited as an autosomal dominant
trait.
• The gene for cherubism was mapped to
chromosome 4p 16.
Clinical features:
• the disease usually occurs between the ages of 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 arises from bilateral
involvement of the posterior mandible that produces
angelic chubby cheeks.
• "eyes upturned to heaven" appearance that is due to
a wide rim of exposed sclerae noted below the iris.

87. • Painless, bilateral
expansion of the posterior
mandible that tends to
involve the angles and
ascending rami.

88. Oral manifestations:
• Agenesis of 2nd and 3rd molars of the mandible.
• Deciduous dentition may be spontaneously shed prematurely
beginning as early as 3 years of age.
• The permanent dentition is often defective with absence of
numerous teeth and displacement and lack of eruption of
those present.
• Based on clinical features- 3 grades.
▫ Grade-i- involvement of both ascending rami Of mandible
▫ Grade-ii- Maxillary tuberosities and ascending rami Of mandible
▫ Grade-iii- Whlole maxilla and mandible except coronoid process
and condyles.

89. Radiographic features:
• Bilateral multilouculated radiolucencies of the posterior mandible and
maxilla
• soap-bubble appearance
• Lesion cause bony expansion and thinning of the cortical plates.
• Numerous unerupted teeth
• Destruction of alveolar bone causes displacement of teeth- Floating
tooth syndrome.
• Ground glass appearance is due to re-ossification in adulthood which
results in patchy sclerosis.

90. Histopathologic Features:
• Clusters of multinucleated
giant cells
• Diffuse background of spindled
mononuclear cells, fresh
hemorrhage
• Eosinophilic fibrinous
material -Eosinophilic cufflike
deposit surrounding small
blood vessels (which is specific
for Cherubism)
Treatment:
• Surgery is rarely indcated.
• The clinical alterations
typically progress until
puberty, then stabilize and
slowly regress.

91. DOWNS SYNDROME
• Also known as trisomy 21
• Is a genetic disorder caused by the presence of
all or part of a third copy of chromosome 21
• Down syndrome is the most common
chromosome abnormality in human beings
• Is a condition in which extra genetic material
causes delays in the way a child develops, both
mentally and physically.

92. Risk factors:
• Advancing maternal age – usually women of age 35
and above
• Mothers who already have one child with Down
syndrome – increased risk for subsequent
pregnancies
• Parents who are carriers of the genetic translocation
for Down syndrome.
Clinical features:
Physical appearances
• Flat facial profile and an upward slant to the eye
• Short neck
• Abnormally shaped ears
• White spots on the iris of the eye (called Brushfield
spots)

93. ORAL MANIFESTATION:
• Relatively late development of deciduous and permanent
teeth as compared with other children
• Teeth could appear in a different sequence and positions
• Teeth are often are rounded, pointed or cone-shaped.
• Maxilla is narrow, the tongue appears too big for the mouth
and the teeth may be pushed out of place, as the child grows
older.
• Habit of breathing through the mouth .
• High arched palate, delayed eruption of teeth, malocclusion
and microdontia are often present
• Fissuring and thickening of the lips and angular cheilitis are
frequent and gets increased in incidence and severity with
age.
• Cheilitis occurs with greater frequency in children with Down
syndrome than in unaffected persons.

94. TREATMENT:
• No treatment
• Dental therapy is directed at prevention of
dental caries and periodontal diseases

95. REFFERENCES:
• Oral Histology and Embryology by Orban, 13th
edition
• Tencate oral histology, 5th edition
• Neville, Oral and Maxillofacial Pathology 2nd
edition
• Shafer`s textbook of oral pathology 6th edition.