Genetics Flashcards
What are the genetics of Duchenne muscular dystrophy?
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
What is the pathophysiology behind Duchenne’s muscular dystrophy?
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:
- Influx of Ca2+
- XS of free radicals
- Myofibre necrosis
- Raised plasma CK
How do children with Duchenne’s muscular dystrophy usually present?
At what age do they usually present?
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
What is Gowers’ sign?
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.
What is the typical life expectancy of a child with Duchenne’s muscular dystrophy? Why is this?
Late 20s
Respiratory failure or associated cardiomyopathy
What is the management of patients with Duchenne’s muscular dystrophy?
Physiotherapy to prevent contractures
Tendoachiles lengthening and scoliosis surgery Overnight CPAP/NIV to manage nocturnal hypoxia secondary to weakness of intercostal muscles
Corticosteroids
What is 47, XXY?
What are the main features of the syndrome?
Klinefelter syndrome
What is 22q11 deletion syndrome?
What are the main features of the syndrome?
DiGeorge syndrome
What is 47XY +21?
Down syndrome
What is 45X?
Turner syndrome
What clinical signs at birth are suggestive down’s syndrome?
Hypotonic infant Flat occiput Single palmar crease Incurved fifth finger Wide 'sandal' gap between the big and second toes
In what 2 syndromes are a fused palmar crease present?
Trisomy 18 (Edward’s) and Trisomy 21 (Down’s)
How is the diagnosis of Down’s syndrome confirmed?
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)
What are some congenital problems that children with down’s syndrome can be born with?
Congenital heart defects (in 40%)
Duodenal atresia
Hirschprung’s disease (<1%)
What 4(/5) things should children with down’s syndrome be screened for periodically?
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
What is the typical cranio-facial appearance of a child with down’s syndrome?
Round face and flat nasal bridge Upslanted palpebral fissures Small mouth and protruding tongue Flat occiput and third fontanelle Epicanthic folds
Also - short neck
What are epicanthic folds?
Skin of the upper eyelid that covers the inner corner of the eye. It runs across the inner edge of the palpebral fissure.
What screening tests are carried out antenatally to look for down’s syndrome?
If an increased risk is identified what is offered?
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
When should the down’s syndrome test be done by?
By 14 weeks (usually done between 10-14 weeks)
What are some other medical problems that can occur with down’s syndrome?
Epilepsy Learning difficulties Short stature Obstructive sleep apnoea Increased risk of leukaemia and solid tumours Increased susceptibility to infections Early-onset Alzheimer's disease
How is turner’s syndrome picked up on US antenatally?
Fetal oedema of the neck, hands or feet OR Cystic hygroma (abnormal growth which occurs on the baby's head or neck)
What percentage of babies with Turner’s result in early miscarriage?
95%
What are some of the features of Turner’s syndrome with regards to the genito-urinary system?
Renal anomalies
Ovarian dysgenesis > Infertility (but pregnancy possible with IVF)
Delayed puberty
What are some of the features of Turner’s syndrome with regards to face and neck?
Neck webbing or thick neck
Recurrent otitis media
What are some of the general features of Turner’s syndrome?
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
What is the treatment of short stature in children with turner’s syndrome?
Growth hormone therapy
Oestrogen replacement for development of secondary sexual characteristics at the time of puberty
