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.
