5. Pathogenesis
• Usually categorised into 3
……> ½ of cases
– Genetically Inherited
• Dorminant / Recessive / X-linked
– Spontaneous Mutations
– Secondary to exposure to toxic substances or
infectious agents resulting in disruption of normal
skeletal dvt
• Mechanisms
– Alteration in transcription of or intra or Extracelluar
processing of structural molecules of skeleton
– Defects in receptor/ Signal transduction pathways of
skeletal differentiation + Proliferation
7. Prenatal Diagnosis
• Currently popular, usually 2nd Trimester
• U/s Shows shortening of skeleton
– Femur length used………..Most Common
– Other – Skull, Spine
• Additional testing can be done by Chorionic Villous Sampling +
Mutation Analysis
8. 2. Achondroplasia
• Point mutation in the
fibroblast growth factor
receptor 3 (FGFR3) that results
in its constitutive activation.
Inhibits chondrocyte proliferation
Suppress expansion of
normal epiphyseal growth plate
Severely stunted long bone growth
9. • Commonest form of Dwarfism…….approx 1.5 : 10000 live births
• Genetics
– Autosomal Dorminant. 80-90% due to spontaneous mutation
Achondroplasia
11. Management of Achondroplasia
• Usually centered around mx of complications
• Spinal Kyphosis
– Non Op… Bracing
– Op………..Ant. Corpectomy + posterior fusion (Kyp >60 by 5yrs)
• Lumbar Stenosis
– Non Op….Wt Loss, Physical therapy, Corticosteroid injections
– Op…………Laminectomy + fusion
• Foramen Magnum Stenosis
– Urgent Decompression
• Genu Valgum
– Tibial osteotomies + Hemiepiphysiodesis
• Controversial
– Growth Hormone therapy + Surgical lengthening of Limbs
12. 1. Osteogenesis
Imperfecta
• Brittle Bone Disease
• Caused by abnormal
type I collagen synthesis
• resulting in bone
fragility and
susceptibility to
fractures.
13. Osteogenesis Imperfecta
• A.k.a Fragilitus Ossium / Brittle Bone Dx
• Pathogenesis
– Impaired mutation Type 1 collagen
– Mutation – COL1A1 & COL1A2 genes
– Impaired cross links preventing production of
polymerized collagen
– Fracture Healing not impaired with large amounts of
callus formation
14. Clinical Manifestations
• Bone fragility and fractures
fractures heal in normal fashion initially
but the bone is does not remodel
can lead to progressive bowing
• Ligamentous laxity
• Short stature
• Scoliosis
• Codfish vertebrae (compressionfx)
• Olecranon apophyseal avulsion fx
16. Clinical Diagnosis
• Symptoms
– Mild Cases – multiple #s during childhood
– Severe - #s at birth. Maybe fatal
• Signs
– Sabre Shin Appearance
– Bowing of bones
– Scoliosis
17. Classification of OI
• Type 1
– Mildest
– Presents at Pre-school age
– Autosomal Dorminant
– Blue Sclera
– Hearing deficit in 50%
– Avulsion #s common due to decreased tensile
strength of bone
• Type 2
– Autosomal Recessive
– Lethal in perinatal period
– Blue Sclera
18. Classification of OI
• Type 3
– Autosomal recessive
– Normal Sclera
– #s at birth
– Progressive short statu
– MOST Severe survivab
re
le form
• Type 4
– Moderately severe
– Autosomal Dorminant
– Bowing of bones + Vertebrae #s common
– Normal Hearing
– White Sclera
Type 5,6,7 added to original
classification.
No real mutation but Abnormal
bone on microscopy
5 – Hypertorphic Callus after #
19. Management
• Fracture
– Prevention
• Early Bracing
Decrease # Incidence
• Bisphosphonates
– Suppress activity of osteoclasts hence px bone mass loss &
resorption
Decrease Deformities
Stabilize Lax Joints
21. 3. Osteopetrosis
• A group of rare genetic
disorders characterized by
reduced osteoclast-mediated
bone resorption defective
bone remodelling
• Result in dense but
architecturally unsound bone
22. 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.
24. 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.