Week 3 - A - Osteogenesis imperfecta, skeletal dysplasias, Congenital C.T.D (Laxity/Marfan/Ehlers-Danlos/Downs), Muscular dystrophies

Question 1

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?

Answer 1

Osteogenesis imperfecta is colloquially known as brittle bone disease

The majority of cases of oseteogensis imperfecta are autosomal dominant

Question 2

What is there a disorder of in osteogenesis imperfecta and what does this cause?

Answer 2

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

Question 3

As stated, the majority of cases of osteogenesis imperfecta are autosoimal dominant How does osteogenesis imperfecta typically present?

Answer 3

Presents with

* Multiple fragility fractures of childhood

* Short stature with multiple deformities

* Blue sclera

* Loss of hearing

Question 4

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?

Answer 4

Multiple fractures can be mistaken for child abuse / Non accidental injury

Scoliosis can result due to the condition

Question 5

How do the bones appear on radiographs in osteogenesis imperfecta?

Answer 5

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.

Question 6

What treatment can be given to try and strengthen the bones in osteogenesis imperfecta? How are fractures generally treated?

Answer 6

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

Question 7

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?

Answer 7

Sofeild procedure is indicated for patients with repetitive fractures of progressive angular deformity

Involves multiple osteotomies and intramedullary stabilisation for correction

Question 8

What is the medical term for short statue as dwarfism is no longer used? What is the commonest and most recognised form of this?

Answer 8

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

Question 9

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?

Answer 9

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)

Question 10

Which chromsomse is the FGFR3 gene found on? What are fibroblasts and what do they produce?

Answer 10

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

Question 11

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?

Answer 11

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

Question 12

What are the presenting features of a child with achondroplasia?

Answer 12

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

Question 13

What is the treatment of achondroplasia?

Answer 13

Treatment comprises of deformity correction (including severe scoliosis correction) and limb lengthening

Growth hormone treatment may be appropriate

Question 14

What are the congenital conenctive tissue disorders due to?

Answer 14

Congenital connective tissue disorders are due to genetic disorders of type 1 collagen synthesis resulting in hypermobility

Question 15

What is the difference between osteogenesis imperfecta and congenital tissue disorders affecting type 1 collagen?

Answer 15

Osteogenesis imperfecta predominantly affects the type 1 collagen of bone whereas the connective tissue disorders affect soft tissues more than bone.

Question 16

Name a simple and popular scoring system that is used to screen for joint laxity and hypermobility?

Answer 16

Beighton Hypermobility Score.

The Beighton score is a simple system to quantify joint laxity and hypermobility.

It uses a simple 9 point system

Question 17

What are the 5 categories used to assess joint hypermobility? (little finger, thumb, elbow, knee, palms)

Answer 17

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

Question 18

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

Answer 18

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

Question 19

What does generalised (familial) joint laxity mean?

Answer 19

Generalised familial joint laxity is when a person’s joints have an unusually large range of movements - hypermobility

Question 20

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?

Answer 20

About 5% of people have generalised familial joint laxity - it is inherited in an autosomal dominant manner

Patients may describe themselves as double jointed

Question 21

What are people with generalised jont laxity (generalised ligamentous laxity) more prone to?

Answer 21

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.

Question 22

What is marfan’s syndrome - ie * State the inheritance * State the mutation * State what it results in

Answer 22

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

Question 23

What is fibrillin essential for?

Answer 23

Fibrillin is essential for the elastic fibres in elastin

Question 24

What are the associated features of marfan syndrome? - think of JOHN * Gross features * Eyes * Lungs * Heart

Answer 24

* 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

Question 25

What is the main danger of death in patients with Marfan’s syndrome?

Answer 25

Aortic dissection is the main risk

Question 26

What is ehler’s danlos syndrome - ie State the inheritance State the mutation

Answer 26

Ehler’s danlos syndrome is a collagen disease usually inherited in an autosomal dominant fashion

The mutation causes an abnormality in type V collagen causing hyperelasticity

Question 27

What are the clinical features of Ehler’s Danlos syndrome?

Answer 27

Profound joint hypermobility Vascular fragility with easy bruising Joint instability Scoliosis Stretchy skin (hyper-extensible skin)

Question 28

Why can bony surgery be a problem for dislocated joints in Ehler’s dnalos syndrome?

Answer 28

Bony surgery may be required for dislocating joints however may be a problem as bleeding can occur and skin healing can be poor with stretched scars or wound dehiscensce

Question 29

What are the musculoskeletal manifestations of trisomy 21 (Down syndrome)?

Answer 29

Musculoskeletal manifestations of Trisomy 21 include

* Short stature

* Joint laxity

* Recurrent dislocation

* Especially patella and atlanto-axial instability

Question 30

Muscular dystrophies are rare What is the mode of inheritance? Which sex is affected? What does it result in?

Answer 30

Muscular dystrophies are rare and usually X-linked recessive disorders

* Therefore only boys are affected

* They result in progressive muscle weakness and wasting

Question 31

What are the two types of muscular dystrophy and what is the gene mutation that occurs in both?

Answer 31

Duchenne muscular dystrophy and Becker’s muscular dystrophy are the two types

In both there is a defect in the dystrophin gene

* In duchenne there is near-total loss of the dystrophin gene

* In Becker’s there is semifunctional dystrophin

Question 32

What is the function of dystophin?

Answer 32

Dystrophin is involved in calcium transport and to muscle and therefore a defect results in muscle weakness

Question 33

When is Duchenne muscular dystrophy commonly noticed? Name the sign that may be noticed in Duchenne muscular dystrophy

Answer 33

Duchenne muscular dystrophy is commonly noticed when boys start to walk with difficulty standing and going up the stairs

Gowers’ sign indicates weakness of the proximal muscles, namely those of the lower limb.

The patient uses their hands and arms to “walk” up their own body from a squatting position due to lack of hip and thigh muscle strength

Question 34

Due to progressive muscle weakness in Duchenne’ muscular dystrophy, when do boys begin to be unable to walk and when is death? (and how)

Answer 34

Progressive muscle weakness causes boys to be unable to walk by the age of 10 and by the age of 20, progressive cardiac and respiratory failure develops with death typically in the early 20s

Question 35

How does Becker’s muscular dystrophy differ from Duchenne?

Answer 35

Becker’s is similar to duchenne however becuase there is semifunctional protein, symptoms are milder and typically later in onset

Boys are bale to walk into their teens and survive into their 30s and 40s

Question 36

How is muscular dystrophy diagnosed?

Answer 36

Muscular dystrophy is diagnosed by raised serum creatinine phosphokinase and abnormalities on muscle biopsy

Question 37

How may mobility be prolonged in muscular dystrophies?

Answer 37

Physiotherapy, splintage and deformity correction may prolong mobility.