GENETIC CONDITIONS Flashcards
Chromosome disorders: TRISOMY
= where the person has an extra chromosome, 3 copies of a particular chromosome
Total of 47 chromosomes
PATAU SYNDROME = trisomy 13
- dysmorphic features, structural abnormalities affecting almost all areas of their body, learning disability
- characteristic “rocker bottom feet” where the soles are covex (rounded outwards) in shape
EDWARDS SYNDROME = trisomy 18
- dysmorphic features and learning disability
- also “rocker bottom” feet
DOWNS SYNDROME = trisomy 21
- most common trisomy condition
Chromosome disorders: Duplication
E.g. Charcot-Marie-Tooth
- duplication of short arm of chromosome 17
- sensory and motor neuropathy and characteristic pes cavus (high arching foot)
Mitochondrial inheritance
Mitochondria comes from mother
Genetic testing
DIAGNOSTIC TESTING: Test a foetus vis amniocentesis
PREDICTIVE TESTING: testing for a specific gene mutation that has implications for them in the future e.g. BRACA1, Huntington’s chorea
CARRIER TESTING: testing for autosomal recessive conditions to calculate risk of passing it to their children
KARYOTYPING: looking at number of chromosomes, their size and basic structure
MICROARRAY TESTING
SPECIFIC GENE TESTING
DNA SEQUENCING (only used for research not clinical)
Down’s syndrome: Dysmorphic Features
- Hypotonia
- Brachycephaly (small head with a flat back)
- Short neck
- Short stature
- Flattened face and nose
- Prominent epicanthic folds (skin covering medial portion of the eye and eyelid)
- upwards sloping palpable fissures (gaps between lower and upper eyelids)
- single palmar crease
Down’s syndrome: Complications
Learning disability
Recurrent otitis media
Deafness
Eustachian tube abnormalities —> glue ear and conductive hearing loss
Visual problems (e.g. myopia, strabismus, cataracts)
Hypothyroidism (10-20%)
Cardiac defects (1 in 3) - particularly ASD, VSD, PDA, ToF
Atlantoaxial instability
Leukaemia is more common in those with downs
Dementia is more common in adults with downs
Down’s syndrome screening: Combined test
COMBINED TEST - first line most accurate test
- between 11-14 weeks gestation
- involves combing results from ultrasound and maternal blood tests
- USS measures nuchal translucency (thickness of back of the neck of foetus)
- MATERNAL BLOOD TEST
- Beta-human chorionic gonadotrophin (Beta-HCG): higher result = greater risk
- Pregnancy-associated plasma protein-A (PAPPA): lower result = greater risk
Down’s syndrome screening: Triple and quadruple tests
TRIPLE TEST
Performed between 14 and 20 weeks
Only involves maternal blood test results
- Beta HCG: higher = greater risk
- Alpha-fetoprotein (AFP): Lower = greater risk
- Serum oestriol (female sex hormone): lower = greater risk
QUADRUPLE TEST
Same as above but also includes maternal test for inhibin-A (higher=greater risk)
Down’s syndrome antenatal testing
If high risk score, mother offered:
AMNIOCENTESIS - US guided aspiration of amniotic fluid using a needle and syringe. Later on in pregnancy once there is enough amniotic fluid to take sample
Or
CHORIONIC VILLUS SAMPLING (CVS) - US guided biopsy of the placental tissue. Used earlier in pregnancy BEFORE 15 WEEKS
Sample of foetal cells undergo KARYOTYPING
Non-invasive prenatal testing
Relatively new test for detecting abnormalities in the foetus during pregnancy
Blood test from mother
Fragments of DNA from placental tissue contained in blood sample - represent fetal DNA
Fragments analysed and detect conditions such as downs
Not a definitive test but gives good indication
Down’s syndrome: Routine follow up investigations
Regular thyroid checks
ECG for cardiac defects
Regular audiometry for hearing impairment
Regular eye checks
Klinefelter Syndrome: genetics
ADDITIONAL X CHROMOSOME (47 XXY)
Klinefelter Syndrome: Features
Usually appear as normal males until puberty, at puberty:
- Taller height
- wider hips
- gynaecomastia
- weaker muscles
- Small testicles
- reduced libido
- shyness
- infertility
- subtle learning difficulties
Klinefelter Syndrome: management
Can’t correct it, aim is to help the features
Testosterone injections
Advanced IVF treatment - has potential to allow fertility
Breast reduction surgery
MDT input (SALT, OT, PT, educational support)
Turners syndrome: Genetics
SINGLE X CHROMOSOME
45 XO
Turners syndrome: features
Short stature **
Webbed neck **
High arching palate
Downward sloping eyes with pots is
Broad chest with widely spaced nipples **
Cubits valgus (abnormal feature of elbow)
Underdevelopment of ovaries with reduced function
Late or incomplete puberty
Most females infertile
Turners syndrome: associated conditions
Recurrent otitis media Recurrent UTIs Coarctation of the aorta Hypothyroidism Hypertension Obesity Diabetes Osteoporosis Various specific learning disabilities
Turners syndrome: Treatment
Treatment not to cure, is to help with symptoms
Growth hormone therapy
Oestrogen and progesterone replacement
Fertility treatment
Noonan syndrome: features
Short stature Broad forehead Downward sloping eyes with pots is Hypertelorism (wide space between the eyes) Prominent nasolabial folds Low set ears Webbed neck Widely spaced nipples
Noonan syndrome: Associated conditions
Congenital heart disease - particularly pulmonary valve stenosis, hypertrophic cardiomyopathy, ASD
Cryptorchidism (undescended testes) can lead to infertility (fertility normal in women)
Learning disability
Bleeding disorders
Lymphoedema
Increased risk of leukaemia and neuroblastoma
Marfan syndrome: Genetic deficits
Autosomal dominant
Affects gene responsible for creating FIBRILLIN (an important component of CT)
Marfans syndrome features
Tall stature Long neck Long limbs Long fingers (arachnodactyly) High arch palate Hypermobility Pectus carinatum or pacts excavatum Downward sloping palpable fissures
Tests for arachnodactyly
- ask them to cross their thumb across their palm - if the thumb tip goes past the opposite edge of the hand this indicates arachnodactyly
- Wrap thumb and finger of one hand around the other wrist, if the thumb and fingers overlap this also indicates arachnodactyly
Marfans syndrome: Cardiac associations
Mitral valve prolapse (with regurgitation)
Aortic valve prolapse (with regurgitation)
Aortic aneurysms
Murmur: mitral regurgitation, aortic regurgitation
Marfans syndrome: other associated conditions
Lens dislocation in the eye Joint dislocations and pain due to hypermobility Scoliosis of the spine Pneumothorax GORD
Marfans syndrome: Management
Greatest risk = cardiac complications (valve prolapse and aortic aneurysms)
- may require surgical correction
Minimise BP and HR to minimise stress on the heart and risk of complications developing
- Lifestyle changes (avoiding intense exercise, caffeine and other stimulants)
- Preventative medications (e.g. beta-blockers, Angiotension II receptor antagonists)
Pregnancy carefully considered - as it carry’s significant risk of developing aortic aneurysms and associated complications
PHYSIOTHERAPY - to strengthen joins and reduce symptoms arising from hypermobility
GENETIC COUNSELLING
Regular follow up - ECG, ophthalmologist
Fragile X syndrome mutation
Mutation in FMR1 (fragile X mental retardation 1) gene on the X chromosome
This gene codes for the fragile X mental retardation protein, which plays a role in cognitive development in the brain
Males always affected, but females can vary with how much they are affected (unclear whether dominant or recessive)
Fragile X syndrome: features
Delay in speech and language development Intellectual disability Long, narrow face Large ears Large testicles after puberty Hyper mobile joints (particularly the hands) ADHD Autism Seizures
Fragile X syndrome: Management
No cure
Supportive management and treat symptoms
MDT - support LD, manage autism and ADHD, treat seizures
Prada-Willi Syndrome: Features
Constant, insatiable hunger that leads to obesity ** Poor muscle tone as an infant (hypotonia) Mild-Moderate learning disability Hypogonadism Fair, soft skin, prone to bruising Mental health problems, particularly anxiety Dysmorphic features Narrow forehead Almond shaped eyes Strabismus Thin upper lip Downturned mouth
Prada-willi syndrome: Management
No cure
Limit access to food under guidance of a dietician (lock on fridge etc)
Lower than normal calorie intake as they usually do less activity due to poor muscle strength and tone
Growth hormone - improving muscle development and body composition
MDT - dieticians, educational support, social workers, physiotherapists, occupational therapists
Angelman syndrome mutation
UBE3A gene (deletion on chromosome mutation)
Specifically the gene inherited from the mother
Angelman syndrome: Features
Delayed development and learning disability Severe delay or absence of speech development Coordination and balance problems (ataxia) Fascination with water ** Happy Demeanour ** Inappropriate laughter Hand flapping Abnormal sleep patterns Epilepsy ADHD Dysmorphic features Microcephaly Fair skin, light hair, blue eyes Wide mouth and widely spaced teeth **
Williams syndrome: features
Broad forehead Starburst eyes (star like pattern on the iris) ** Flattened nasal bridge Long philtrum Wide mouth and widely spaced teeth ** Small chin Very sociable trusting person ** Mild LD
Williams syndrome associations
Supravalvular aortic stenosis (narrowing just above the aortic valve)
Hypercalcaemia
Hypertension
ADHD
Williams syndrome: Management
No cure, managment = MDT approach
ECG and blood pressure monitoring (assess for aortic stenosis and hypertension)
Low calcium diet - avoid calcium and vitD supplements
