clinical

2. Genetic disorders of bone
Brig.Naveed Hussain Syed
HOD Surgery Department
CMH Bahawalpur

3. Bone Disease
Congenital
Osteogenesis
Imperfecta
Achondroplasia
Osteopetrosis
Osteoporosis
Paget Disease
(Osteitis
Deformans)
Acquired
Rickets and
Osteomalacia
Hyperpara-
thyroidism

4. Types

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

6. Some Dysplasias in Detail
You don’t know anything Jon snow

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

10. Short Stature, Fingertips
reaching to the level of
hips
Frontal bossing,
enlargement of head
Star fish hand, Trident
hand

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

15. Non-Orthopaedic manifestations
• Blue sclera
• Hearing loss
lessfrequentthangeneralysuspected
• Dentinogenesis imperfecta
brownish opalescent teeth
• Wormian skull bones
(puzzlepieceintrasuturalskul bones)

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

20. Management
• Fracture Treatment
– Non op if < 2ys
– Op
• Pt > 2ys
– Scoliosis
• Operative – posterior fusion

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.

25. Have an Orthopedic
Day
Teacher
Student
EXAM
Dr.Virinderpal Singh Chauhan

26. CMH BWP
Thank you