Week 3 - A - Osteogenesis imperfecta, skeletal dysplasias, Congenital C.T.D (Laxity/Marfan/Ehlers-Danlos/Downs), Muscular dystrophies Flashcards
What congenital disorder of the musculoskeletal system is known colloquially as brittle bone disease? What is the inheritance of the majority of cases with this condition?
Osteogenesis imperfecta is colloquially known as brittle bone disease
The majority of cases of oseteogensis imperfecta are autosomal dominant
What is there a disorder of in osteogenesis imperfecta and what does this cause?
In osteogenesis imperfecta, there is a defect of the maturation and organisation of type 1 collagen
As type 1 collagen accounts for most of the organic composition of bone, this results in fragile, low density bones which are more likely to fracture
As stated, the majority of cases of osteogenesis imperfecta are autosoimal dominant How does osteogenesis imperfecta typically present?
Presents with
* Multiple fragility fractures of childhood
* Short stature with multiple deformities
* Blue sclera
* Loss of hearing
What can the multiple childhood fractures in osteogenesis imperfecta be mistaken for? What is the spinal deformity that affects te majority of adults witht he condition?
Multiple fractures can be mistaken for child abuse / Non accidental injury
Scoliosis can result due to the condition
How do the bones appear on radiographs in osteogenesis imperfecta?
On radiographs, the bones appear osteoporotic with thin cortices and bowing deformity of the bones
Mild cases may have relatively normal xrays with history of low energy fractures.
What treatment can be given to try and strengthen the bones in osteogenesis imperfecta? How are fractures generally treated?
Biphosphonates can be given to try and strengthen the bones (reduces osteoclast activity)
Fractures tend to heal with abundant but poor quaity callus - treated with splintage, traction or surgical stabilisation
Some cases develop progressive deformity or repetitive fractures What is the procedure known as that may be used to treat these patients? What happens in this proceure?
Sofeild procedure is indicated for patients with repetitive fractures of progressive angular deformity
Involves multiple osteotomies and intramedullary stabilisation for correction
What is the medical term for short statue as dwarfism is no longer used? What is the commonest and most recognised form of this?
Skeletal dysplasia is the medical term for short statue as dwarfism is no longer used
The commonest and most recognised form of skeletal dysplasia is achondroplasia
Skeletal dysplasia is due to genetic error (hereditary or sporadic (de novo) mutation) resulting in abnormal development of bone and connective tissue What is the inheritance of achondroplasia? What is the mutation that occurs in this condition?
Achondroplasia has an autosomal dominant inheritance however 80% of cases are sporadic
The majority of cases (95%) are caused by a mutation in the gene encoding fibroblast growth factor receptor 3 (FGFR3)
Which chromsomse is the FGFR3 gene found on? What are fibroblasts and what do they produce?
FGFR3 is located on the short arm of chromosome 4
Fibroblasts are cells in the connective tissue and in the dermis of skin that make collagen and other fibres
More than 300 types of skeletal dysplasia have been described What is the difference between proporitonate and disproportionate short stature that may occur in skeletal dysplasias?
Short stature may be
* Proprtionate- where the limbs and spine are proportionally short
* Disproportionate - where the limb are proportionally shorter or longer than the spine
What are the presenting features of a child with achondroplasia?
Achondroplasia results in
* disproportionately short limbs (shorter limbs with normal trunk length)
* with short, same length fingers
* with a prominent forehead (frontal bossing)
* & widened nose
Gross motor skills develop later in these children
What is the treatment of achondroplasia?
Treatment comprises of deformity correction (including severe scoliosis correction) and limb lengthening
Growth hormone treatment may be appropriate
What are the congenital conenctive tissue disorders due to?
Congenital connective tissue disorders are due to genetic disorders of type 1 collagen synthesis resulting in hypermobility
What is the difference between osteogenesis imperfecta and congenital tissue disorders affecting type 1 collagen?
Osteogenesis imperfecta predominantly affects the type 1 collagen of bone whereas the connective tissue disorders affect soft tissues more than bone.
Name a simple and popular scoring system that is used to screen for joint laxity and hypermobility?
Beighton Hypermobility Score.
The Beighton score is a simple system to quantify joint laxity and hypermobility.
It uses a simple 9 point system
What are the 5 categories used to assess joint hypermobility? (little finger, thumb, elbow, knee, palms)
Passively dorsiflex little finger greater than 90 degrees (R+L)
Passively oppose thumb to volar aspect of the ipsilateral forearm (R+L)
Passively hyperextend elbow greater than 10 degrees (R+L)
Passively hyperextend knee greater than 10 degrees (R+L)
Hands can rest flat on floor when flexing the trunk with extended knees
Select which of the following statements are true of the Beighton classification of joint Hypermobility
a. The ability to place both palms on the floor when bending with straight legs
b. A score of 2 or more confirms the diagnosis of hypermobility
c. The ability to passively touch the forearm with the thumb with the wrist in the flexed position scores one point per wrist
. d. > 10 degrees of hyperextension at the elbow
e. There are a total of 9 criteria in the scoring system
TRUE:
a. The ability to place both palms on the floor when bending with straight legs
c. The ability to passively touch the forearm with the thumb with the wrist in the flexed position scores one point per wrist.
d. > 10 degrees of hyperextension at the elbow
e. There are a total of 9 criteria in the scoring system
Score of 4 or more is a good indicator of hypermobility
What does generalised (familial) joint laxity mean?
Generalised familial joint laxity is when a person’s joints have an unusually large range of movements - hypermobility
What percentage of people have hypermobility of the joints which usually runs in families? - generalised familial joint laxity What is the inheritance? How may patients describe themselves?
About 5% of people have generalised familial joint laxity - it is inherited in an autosomal dominant manner
Patients may describe themselves as double jointed
What are people with generalised jont laxity (generalised ligamentous laxity) more prone to?
People with generalized ligamentous laxity are more prone to soft tissue injuries (ankle sprains) and recurrent dislocations of joints (especially shoulder and patella) which may be painful.
What is marfan’s syndrome - ie * State the inheritance * State the mutation * State what it results in
Marfan’s syndorme is a connective tissue disorder that is autosmal dominant or sporadic mutation of the fibrillin gene
This results in tall stature with disproportionately long limbs and ligament laxity
What is fibrillin essential for?
Fibrillin is essential for the elastic fibres in elastin
What are the associated features of marfan syndrome? - think of JOHN * Gross features * Eyes * Lungs * Heart
* Gross features - Tall stature, Disproportionately long limbs, Ligamentous laxity, Pectus excavatum(pigenon chest) or carinatum (sternal protrusion), arachnodactyly (long fingers and toes)
* Eye problems - Lens dislocation, retinal detachment
* Lungs - Spontaneous pneumothorax, apical blebs
* Heart - Aotic dissection, aneurysm, regurgitation
