Congenital Disorders of the MSK System

Question 1

What is osteogenesis imperfecta?

Answer 1

A rare genetic disorder affecting connective tissue, primarily bones, causing increased fragility—also known as brittle bone disease

Question 2

What is the primary molecular defect in osteogenesis imperfecta?

Answer 2

Abnormal maturation and organisation of type I collagen

Question 3

What is the most common inheritance pattern of osteogenesis imperfecta?

Answer 3

Autosomal dominant

Question 4

What are classic clinical features of osteogenesis imperfecta?

Answer 4

1. Multiple childhood fractures
2. Short stature
3. Skeletal deformities
4. Blue sclerae
5. Dentinogenesis imperfecta
6. Hearing loss

Question 5

Why can osteogenesis imperfecta be mistaken for non-accidental injury?

Answer 5

Due to the presence of multiple fractures at various stages of healing

Question 6

What ocular feature is commonly seen in OI and why?

Answer 6

Blue sclerae
= due to thin collagen layers in the sclera revealing underlying choroid

Question 7

How do autosomal recessive forms of osteogenesis imperfecta differ from dominant ones?

Answer 7

They are more severe
= often lethal in the perinatal period or associated with significant spinal deformities

Question 8

What do X-rays show in osteogenesis imperfecta?

Answer 8

1. Thin (gracile) bones
2. Thin cortices and osteopenia
3. Some mild cases may have nearly normal X-rays despite a fracture history

Question 9

What are the potential complications of osteogenesis imperfecta beyond bone fractures?

Answer 9

(1) Spinal deformities

(2) Hearing loss

(3) Dental abnormalities

Question 10

What are the key management strategies for osteogenesis imperfecta?

Answer 10

1. Fracture management
   = splinting, casting, surgical stabilisation
2. Bisphosphonates
3. Physiotherapy
4. Orthopaedic surgery
5. Audiology support
   = monitor and treat hearing loss
6. Dental

Question 11

What is the most common and mildest form of osteogenesis imperfecta?

Answer 11

Type 1, which presents in childhood with bone fragility but relatively good prognosis

Question 12

What is the underlying biochemical defect in osteogenesis imperfecta type 1?

Answer 12

Reduced synthesis of pro-alpha 1 or pro-alpha 2 chains of type I collagen

Question 13

Are biochemical bone markers such as calcium and phosphate abnormal in osteogenesis imperfecta?

Answer 13

NO

Question 14

A 4-year-old boy presents to the emergency department with a suspected fractured femur. He has had several visits over the past few months. On examination, his teeth appear abnormal and he is very skinny. His father is also concerned about the boy’s hearing.

What is the most likely diagnosis?

Answer 14

Osteogenesis imperfecta

Question 15

What is skeletal dysplasia?

Answer 15

A group of genetic conditions causing abnormal bone and connective tissue development, often leading to short stature

Question 16

What is the most common type of skeletal dysplasia?

Answer 16

Achondroplasia

Question 17

Is achondroplasia inherited?

Answer 17

It can be autosomal dominant, but over 80% are new (sporadic) mutations

Question 18

Describe the typical appearance of achondroplasia.

Answer 18

1. Disproportionately short limbs
2. Prominent forehead
3. Widened nose
4. Normal intelligence

Question 19

What’s the difference between proportionate and disproportionate short stature?

Answer 19

Proportionate
= spine and limbs equally short

Disproportionate
= One shorter than the other
(eg, limbs shorter than the spine)

Question 20

What is Duchenne Muscular Dystrophy and who does it primarily affect?

Answer 20

Rare X-linked recessive disorder that almost exclusively affects boys

= leading to progressive muscle wasting

Question 21

What is the underlying genetic defect in Duchenne Muscular Dystrophy?

Answer 21

A mutation in the dystrophin gene, which is crucial for maintaining muscle cell integrity and calcium transport

Question 22

What is Gower’s sign and what condition is it associated with?

Answer 22

Gower’s sign is when a child uses their hands to “climb up” their thighs to stand, due to proximal muscle weakness

= It is seen in Duchenne Muscular Dystrophy

Question 23

When do symptoms of Duchenne Muscular Dystrophy typically begin?

Answer 23

Symptoms usually start around the time a child begins to walk, often with difficulty climbing stairs or standing up

Question 24

What is the typical progression of muscle weakness in Duchenne Muscular Dystrophy?

Answer 24

(1) It starts in the legs
(2) progresses to involve the upper limbs

(3) eventually affects respiratory and cardiac muscles.

Question 25

By what age are most boys with DMD no longer able to walk?

Answer 25

By about 10 years old

Question 26

What are the typical causes of death in Duchenne Muscular Dystrophy?

Answer 26

Cardiac and respiratory failure, usually by the early 20s

Question 27

What blood test is characteristically raised in DMD?

Answer 27

Serum creatine phosphokinase (CK) is significantly elevated

Question 28

What diagnostic procedure confirms DMD?

Answer 28

Muscle biopsy, showing absent or abnormal dystrophin

Question 29

What are some key elements of managing Duchenne Muscular Dystrophy?

Answer 29

Physiotherapy, splinting, deformity correction, and spinal surgery for scoliosis

Question 30

A four-year-old boy has presented with his concerned mother with an abnormal gait and weakness in his lower limbs. A history, examination and subsequent investigations are completed and he is diagnosed with Duchenne muscular dystrophy. What is the most common cardiac pathology associated with this condition?

Answer 30

Dilated cardiomyopathy

Question 31

A concerned mother brings her 4-year-old son to see the GP, worried about his walking and balance. The child learned to walk around 2 years old, much the same as his older sister. However, over the last few months, his mum has noticed that he has become reluctant to walk and often trips or falls when he does. On examination, the child is slim built but has disproportionately large calves. When asked to walk across the room he does so on his tiptoes. Gowers's test is positive. What investigation is considered most appropriate to confirm the likely diagnosis?

Answer 31

Genetic test

Question 32

Describe Gower’s sign

Answer 32

1. Get on all fours 2. Push their bottom up into the air (so they're kind of in a bear crawl position) 3. Then use their hands on their thighs to “walk” their upper body upright — like they’re climbing up their legs