Genetics Flashcards
What are chromosome disorders?
- structural abnormalities
- extra abnormal portion
- abnormal number
of chromosomes.
What are deletion disorders?
A portion of the chromosome is missing.
What are translocation disorders?
One portion of one chromosome is directly swapped with a portion of another chromosome.
What is trisomy?
A person has an extra copy of a chromosome, meaning they have a total of 47 chromosomes.
What is mosaicism?
A chromosomal abnormality that occurs after conception, meaning there is an anomaly in a portion of cells in the body and not in others.
Principles of mitochondrial inheritance.
At the time of conception, the sperm carrying the father’s genetic material enters the oocyte and the DNA in the nucleus of both cells combine.
As mitochondrial DNA is located in the tail of the sperm, which does not enter the oocyte, the mitochondrial DNA of the zygote is of maternal origin.
What is karyotyping?
Looking at the number of chromosomes, their size and basic structure.
Pathophysiology of Down’s syndrome.
Three copies of chromosome 21 (trisomy 21), gives dysmorphic features.
Dysmorphic features of Down’s syndrome.
- hypotonia
- brachycephaly
- short neck
- short stature
- flattened face and nose
- single palmar crease
- prominent epicanthic folds
- upward sloping palpebral fissure
Complications of Down’s syndrome.
- learning disability
- recurrent otitis media
- deafness
- visual problems
- hypothyroidism
- cardiac defects (e.g. ASD, VSD, tetralogy of Fallot)
- leukaemia
- dementia
What is the combined test for Down’s syndrome?
Antenatal screening at weeks 11-14 gestation:
1) Ultrasound showing nuchal thickness
2) Bloods showing elevated b-hCG and low PAPPA
What is the triple test for Down’s syndrome?
Antenatal screening at weeks 14-20 gestation:
1) Raised b-hCG
2) Low AFP
3) Low serum oestriol
How is Down’s syndrome antenatally tested for?
Combined / triple test for screening.
If screening results significant, a sample of fetal cells can be taken and sent for karyotyping:
- amniocentesis
- chorionic villus sampling
Management of Down’s syndrome.
Supportive care from the multidisciplinary team:
- occupational therapy
- SALT
- physiotherapy
- dietician
- paediatrician
- GP
- health visitors
- cardiologist
- ENT specialist
- optician
- social services
- support with educational needs
- Down’s syndrome association
Routine investigations in Down’s syndrome.
- thyroid checks every 2 years
- echocardiogram to diagnose cardiac defects
- regular audiometry for hearing impairment
- regular eye checks for visual impairment
Prognosis of Down’s syndrome.
Depending on severity of associated complications - mean life expectancy is 60 years.
Aetiology of Klinefelter syndrome.
Male has an additional X chromosome (47 XXY)
Features of Klinefeter syndrome.
Normal development until puberty, then:
- tall
- wide hips
- gynaecomastia
- weak muscles
- small testicles
- reduced libido
- shyness
- infertility
- subtle learning difficulty
Management of Klinefelter syndrome.
- testosterone injections for symptomatic improvement
- advanced IVF treatment to enable fertility
- breast reduction surgery for cosmetic purposes
MDT team involved:
- SALT to improve speech and language
- occupational therapy
- physiotherapy to strengthen muscles and joints
- educational support for learning difficulties
Prognosis of Klinefelter syndrome.
Slight increased risk of:
- breast cancer
- osteoporosis
- diabetes
- anxiety and depression
Life expectancy is close to normal.
Infertility can sometimes be managed with IVF techniques.
Aetiology of Turner syndrome.
Female has a single X chromosome (45XO).
Features of Turner syndrome.
- short stature
- webbed neck
- wide nipples
- infertility
- late or incomplete puberty
Associations of Turner syndrome.
- recurrent otitis media
- recurrent UTIs
- coarctation of the aorta
- hypothyroidism
- obesity
- diabetes
- osteoporosis
- learning difficulties
Management of Turner syndrome.
- growth hormone therapy to prevent short stature
- oestrogen and progesterone replacement to establish secondary sexual characteristics
- fertility treatment to increase the chances of becoming pregnant.
Inheritance pattern of Noonan syndrome.
Autosomal dominant
Features of Noonan syndrome.
- short stature
- broad forehead
- wide space between the eyes
- low set ears
Associated conditions to Noonan syndrome.
- congenital heart disease
- undescended testes, leading to infertility*
- learning disability
- bleeding disorders
- lymphoedema
- increased risk of leukaemia and neuroblastoma
Management of Noonan syndrome.
Supportive management by multidisciplinary team.
Main complication is congenital heart disease requiring corrective surgery.
Inheritance pattern of Marfan syndrome.
Autosomal dominant
Pathophysiology of Marfan syndrome.
Genetic condition affecting the gene responsible for creating fibrillin, resulting in abnormal connective tissue.
Features of Marfan syndrome.
- tall stature
- long neck
- long limbs
- long fingers
- high arch palate
- hypermobility
Conditions associated with Marfan syndrome.
- lens dislocation in the eye
- joint dislocation and pain due to hypermobility
- scoliosis of the spine
- pneumothorax
- GORD
- mitral valve regurgitation
- aortic valve regurgitation
- aortic aneurysms
Management of Marfan syndrome.
Greatest risk is from associated cardiac complications:
- surgical correction
- avoid intense exercise
- avoid caffeine
- beta blockers or ARBs
- carefully consider pregnancy
Physiotherapy can be helpful in strengthening joints.
Genetic counselling.
Yearly echocardiograms and review by opthalmology.
Pathophysiology of Fragile X syndrome.
Mutation in FMR1 gene, which does for the fragile X mental retardation protein.
The fragile X mental retardation protein plays a role in cognitive development in the brain.
Inheritance pattern of Fragile X syndrome.
X-linked
No evidence to suggest dominant or recessive.
Features of Fragile X syndrome.
- intellectual disability
- long, narrow face
- large ears
- large testicles after puberty
- hypermobile joints
- ADHD
- autism
- seizures
Management of Fragile X syndrome.
Multidisciplinary team to manage the condition.
Life expectancy is similar to the general population, however may be reduced depending on associated disabilities or complications.
What is Prader-Willi syndrome?
Loss of functional genes on the proximal arm of chromosome 15 inherited from the father:
- due to deletion
- both copies of chromosome 15 inherited from mother
Features of Prader-Willi syndrome.
- constant hunger, leading to obesity
- hypotonia
- learning disability
- hypogonadism
- fair, soft skin
- dysmorphic features
- narrow forehead
- thin upper lip
- do
Management of Prader-Willi syndrome.
NICE recommend treatment with growth hormone, to improve muscle development and body composition.
Supportive care from MDT:
- dieticians
- education support
- social workers
- psychologists or psychiatrists
- physiotherapist
- occupational therapists
What is William syndrome?
Random deletion of genetic material on one copy of chromosome 7.
Features of William syndrome.
- starburst eyes
- flattened nasal bridge
- small chin
- sociable, trusting personality
- mild learning disability
Conditions associated with William syndrome.
- supravalvular aortic stenosis
- hypercalcaemia
- hypertension
- hypercalcaemia
Management of William syndrome.
MDT approach.
Echocardiograms and blood pressure monitoring.
Low calcium diet - avoid calcium and vitamin D supplements.
