Genetics

Question 1

What are the genetics of Duchenne muscular dystrophy?

Answer 1

It is an X linked recessive disorder
2/3 of cases are inherited from the persons mother
1/3 of cases are due to a new mutation

Question 2

What is the pathophysiology behind Duchenne’s muscular dystrophy?

Answer 2

Deletion of the gene for dystrophin
Dystrophin normally connects the cytoskeleton of a muscle fibre to the surrounding extracellular matrix through the cell membrane

Where it is deficient there is:

1. Influx of Ca2+
2. XS of free radicals
3. Myofibre necrosis
4. Raised plasma CK

Question 3

How do children with Duchenne’s muscular dystrophy usually present?
At what age do they usually present?

Answer 3

Usually present ages 5 but children often become symptomatic much earlier

Usually present with waddling gait and/or language delay
Have to mount stairs one by one
Show Gowers’ sign

Question 4

What is Gowers’ sign?

Answer 4

It is a medical sign that indicates weakness of the proximal muscles, namely those of the lower limb.
The sign describes a patient that has to use their hands and arms to “walk” up their own body from a squatting position due to lack of hip and thigh muscle strength.

Question 5

What is the typical life expectancy of a child with Duchenne’s muscular dystrophy? Why is this?

Answer 5

Late 20s

Respiratory failure or associated cardiomyopathy

Question 6

What is the management of patients with Duchenne’s muscular dystrophy?

Answer 6

Physiotherapy to prevent contractures
Tendoachiles lengthening and scoliosis surgery Overnight CPAP/NIV to manage nocturnal hypoxia secondary to weakness of intercostal muscles
Corticosteroids

Question 7

What is 47, XXY?

What are the main features of the syndrome?

Answer 7

Klinefelter syndrome

Question 8

What is 22q11 deletion syndrome?

What are the main features of the syndrome?

Answer 8

DiGeorge syndrome

Question 9

What is 47XY +21?

Answer 9

Down syndrome

Question 10

What is 45X?

Answer 10

Turner syndrome

Question 11

What clinical signs at birth are suggestive down’s syndrome?

Answer 11

Hypotonic infant
Flat occiput
Single palmar crease 
Incurved fifth finger
Wide 'sandal' gap between the big and second toes

Question 12

In what 2 syndromes are a fused palmar crease present?

Answer 12

Trisomy 18 (Edward’s) and Trisomy 21 (Down’s)

Question 13

How is the diagnosis of Down’s syndrome confirmed?

Answer 13

It is confirmed with a blood test
Before the blood is sent for analysis parents should be informed that a blood test for Down’s syndrome is being performed
The results may take 1-2 days using real-time PCR (rtPCR) or rapid fluorescence in situ hybridisation (FISH)

Question 14

What are some congenital problems that children with down’s syndrome can be born with?

Answer 14

Congenital heart defects (in 40%)
Duodenal atresia
Hirschprung’s disease (<1%)

Question 15

What 4(/5) things should children with down’s syndrome be screened for periodically?

Answer 15

Impairment of vision and hearing
- Can get hearing impairment from secretory otitis media
- Can get visual impairment from cataracts, squint and myopia
Hypothyroidism
Coeliac disease
Atlantoaxial instability

Question 16

What is the typical cranio-facial appearance of a child with down’s syndrome?

Answer 16

Round face and flat nasal bridge
Upslanted palpebral fissures 
Small mouth and protruding tongue
Flat occiput and third fontanelle
Epicanthic folds

Also - short neck

Question 17

What are epicanthic folds?

Answer 17

Skin of the upper eyelid that covers the inner corner of the eye. It runs across the inner edge of the palpebral fissure.

Question 18

What screening tests are carried out antenatally to look for down’s syndrome?
If an increased risk is identified what is offered?

Answer 18

Nuchal thickening on US
Biochemical markers in blood samples

If an increased risk is identified, amniocentesis or chorionic villous sampling are offered to check the fetal karyotype

Question 19

When should the down’s syndrome test be done by?

Answer 19

By 14 weeks (usually done between 10-14 weeks)

Question 20

What are some other medical problems that can occur with down’s syndrome?

Answer 20

Epilepsy
Learning difficulties
Short stature
Obstructive sleep apnoea
Increased risk of leukaemia and solid tumours
Increased susceptibility to infections
Early-onset Alzheimer's disease

Question 21

How is turner’s syndrome picked up on US antenatally?

Answer 21

Fetal oedema of the neck, hands or feet OR
Cystic hygroma (abnormal growth which occurs on the baby's head or neck)

Question 22

What percentage of babies with Turner’s result in early miscarriage?

Answer 22

95%

Question 23

What are some of the features of Turner’s syndrome with regards to the genito-urinary system?

Answer 23

Renal anomalies
Ovarian dysgenesis > Infertility (but pregnancy possible with IVF)
Delayed puberty

Question 24

What are some of the features of Turner’s syndrome with regards to face and neck?

Answer 24

Neck webbing or thick neck

Recurrent otitis media

Question 25

What are some of the general features of Turner’s syndrome?

Answer 25

Short stature (a cardinal feature!)
Pigmented moles
Widely spaced nipples

Lymphoedema of hands and feet in the neonate
Spoon-shaped nails
Congenital heart defects
Hypothyroidism

Question 26

What is the treatment of short stature in children with turner’s syndrome?

Answer 26

Growth hormone therapy

Oestrogen replacement for development of secondary sexual characteristics at the time of puberty