Presentation on the congenital and developmental diseases of the bone in series. First is osteogenesis imperfecta

1. Congenital and Developmental
Disorders of the Bone
by
Dr. Stephen Yusuf
ATBUTH, Bauchi. Nigeria.

2. 1.
Osteogenesis imperfecta
BRITTLE BONE

3. Outline
• Introduction
• Pathology
• Clinical features
• Radiological features
• Laboratory features
• Classification
• Management
• History
• Examination
• Investigation
• Treatment

4. Introduction
• It is one of the commonest of genetic disorders of bone
• It has an estimated incidence of 1 in 20 000
• It is due to abnormal synthesis and structure of type 1 collagen
• Which result in abnormalities of ;
• Bones
• Teeth
• Ligaments
• Sclera
• skin

5. Introduction
• The defining clinical features of OI are :
1. Osteopenia
2. Liability to fracture
3. Laxity of ligaments
4. Blue coloration of sclera
5. Dentinogenesis imperfecta

6. Pathology
• The genetic abnormality presents as an alteration in structural
integrity
• Or a reduction in the total amount of type 1 collagen
• Even small alteration in composition of type 1 collagen can lead to
weakening of these tissues
• And imperfect ossification in all types of bones

7. Pathology
• OI is caused by a dominant mutation in the COL1A1 or the COL1A2
genes that encode type 1 collagen
• Fewer than 10 percent of OI are caused by recessive mutation
• There is increase production of abnormal type 1collagen and
decrease production of normal type 1 collagen
• Due to mutation in the loci coding for pro- α1 and pro- α2 chain that
form the helical structure of collagen 1

8. Clinical features
• These varies considerably according to the severity of the condition
• The most striking abnormality is the propensity to fracture
• Generally after minor trauma and often without much pain or
swelling
• Fracture are discovered during infancy and they recur throughout
childhood

9. Clinical features
• Callus deposition is florid
• But the new bone is abnormal and remains pliable predisposing to
malunion and increase risk of refracture
• By the age of 6 years there may be severe deformities of the long
bones and vertebral compression fracture leading to kyphoscoliosis
• After puberty, fracture occur less frequently

10. Clinical features
• Skin is loose
• Joint is hypermobile
• Blue or grey sclera due to uveal pigment showing through the
hypertrasluscent cornea
• Teeth may be colored and carious

11. Radiographic features
• These vary accodrding to the type of disease and severity
• There is generalised osteopenia
• Thinning of long bones
• Fractures at various stages of healing
• Vertebral compression and deformity

12. • Enlarged skull with wormian bones
• Fractures healed with florid calluses mimicking osteosarcoma
• Bones are thin and under tubulated- gracile
• In severe form diagnosis can be made by ultrasound scan in second
trimester –
• Diagnostic features include; cranial enlargement, reduced
echogenicity of bone and deformity and shortening of limbs ( due to
intrauterine fractures)

13. Laboratory investigations
• Calcium and phosphorus are normal
• Alkaline phosphatase is elevated

14. Forms of OI
• Congenita – this has short life expectancy
• Tarda --- normal life expectancy

15. Classification of OI
• The clinical variants of OI can be divided into sub groups
• Showing well defined difference in the
• Pattern of inheritance
• Age of presentation
• Severity of changes in bone and extra skeletal tissues
Which can be helpful in assessing prognosis and planning treatment
for any particular patient

16. Classification (silence (1981)
Type 1 (mild)
• It’s the commonest variety (>50% of all cases)
• Fractures appear at 1-2years of age
• Healing is good and deformities not marked
• Sclera deep blue
• Teeth usually normal but some have dentigenous imperfect
• Impaired healing in adult
• Autosomal dominant inheritance
• Normal life expentancy

17. Type 2 (lethal)
• 5-10% of cases
• Intrauterine and neonatal fractures
• Large skull and wormian bones
• Sclera grey
• Rib fractures and respiratory difficulties
• Stillborn or survives for few weeks
• New dominant mutation or recessive

18. Type 3 (severe deforming )
• It’s the classic but not the most common , form of OI
• Fracture at birth
• Large skull and wormian bone , pinched looking face
• Marked deformities and kyphoscoliosis at 6years
• Sclera grey then white

19. • Dentigenoius imperfect
• Marked joint laxity
• Respiratory problems
• Poor quality of life. Few survive to adulthood
• Sporadic or autosomal recessive inheritance

20. Type 4 (moderately severe )
• Uncommon, <5% of cases
• Frequent fracture during early childhood
• Deformities common
• Sclera pale blue or normal
• Dentinogenesis imperfecta
• Survive to adulthood with fairly good function
• Autosomal dominant inheritance

21. OI

22. Management
• History
• There is no sex or race predilection
• Familial history
• Hx of stillbirth in the mother and possible cause/ features of the stillborn
• Hx of recurrent fractures
• History of shortening and mal-unions
• Delay in ambulation/ non ambulant

23. • Examination
• Facial features- triangular facial feature
• Frontal bossing
• Pectus carinatum/ barrel shaped chest
• Kyphoscoliosis /curved spine
• Bowing of the long bones and multiple healed fractures
• With malunion
• Blue sclera
• Easy bruisability of skin
• Loose joints

24. Examination ctd
• Discolored teeth
• Malocclusion of the teeth/ malaligned
• Breathing problem
• Coxa vara
• Joint contractures

25. Investigations
• Prenatal DNA mutation analysis to analyze uncultured chorionic villi
• Prenatal evaluation with USS in 2nd trimester
• X-ray
• Bone biopsy for histology and genetic studies
• SDS PAGE
• 2-Dimentional SDS-PAGE
• Cyanogen bromide mapping

26. Treatment
• No medical treatment that will counteract the effect of this
abnormality
• Genetic manipulation in the future maybe
• Conservative treatment is directed at preventing fractures
• Using lightweight orthosis during physical activities

27. • Treating fractures when they occur
• Splintage should not be overdone as it can worsen osteopenia
• Measures to prevent recurring trauma
• Measures to encourage social adaptation
• Cyclical bisphosphonate to increase bone mineral density and reduce
tendency to fracture
• Fractures are treated conservatively

28. • Long bone deformities due to recurrent fractures and malunion can
be corrected operatively
• Operative management by 5 or 6 years
• Multiple osteotomies are performed and bone fragments aligned on
strait intramedullary rods
• Telescoping nails can be used to solve the problem of the bone
outgrowing the rods
• Telescoping nails however hold high complication rates

29. Telescoping nails

30. Telescoping nails

31. • Spinal deformities can be handled operative instrumentation and
spinal fusion
• Bracing is ineffective
• After adolescent fractures are relatively uncommon and patient can
pursue a fairly normal life

32. Differentials
• Achondroplasia
• Battered baby syndrome
• Glucocorticoid theraphy and cushing syndrome
• Homocystinuria/homocysteinemia
• McCune-Albright syndrome
• Osteopetrosis
• Osteoporosis
• Rickets
• Scurvy
• Wilson disease