Genetic Conditions Flashcards
What is the different between phenotype and genotype?
Genotype= the genes that we have Phenotype= the physical expression of the genes that we have
What is mendelian inheritance?
This type of inheritance occurs when there is a disease caused by a single abnormal gene on one of the non sex chromosomes
What is a chromosome disorder?
Conditions where there is either a structural abnormality, an extra abnormal portion or an abnormal number of chromosomes compared to normal.
What is an example of a chromosome deletion disorder?
Cri du chat which presents with a cat like cry
What is a chromosomal duplication disorder?
This occurs where a portion of chromosome is duplicated
What is an example of a chromosomal duplication disorder?
Charcot Marie tooth
Sensory and motor neuropathy soth characteristic high arched feet
What is a translocation disorder?
Occurs where a portion of one chromosome is directly swapped with another chromosome.
The swap can be balanced (reciprocal translocations)
Unbalanced (nonreciprocal translocations) this is where a portion of the chromosome leaves the first chromosome and attaches to another without an exchange taking place.
What does translocation usually cause?
Translocation does not usually lead to a specific genetic syndrome but often predisposes to other conditions such as cancer and infertility
When does the philadelphia chromosome translocation occur?
This is a reciprocal translocation between chromosome 9 and 22 and it occurs in acute myeloid leukaemia.
Trisomy is when the person has an extra chromosome, what are the 3 trisomys which you should know about?
Patau syndrome
This is a trisomy 13
Edwards syndrome
This is a trisomy 18
Downs
This is trisomy 21
What is mosaicism?
This is where the chromosomal abnormality actually happens after conception. The abnormality occurs in portions of the cells in the body and not in others and is unpredictable.
What is predictive testing?
Involves testing a person for a specific gene mutation that has implications for them in the future
Ie: BRCA1 gene or the gene for huntingtons
What is karyotyping?
Involves looking at the number of chromosomes, their size and their basic structure
It is useful in diagnosing DOWN syndrome (trisomy 21) and turner syndrome (45XO)
What are the features of downs syndrome?
Hypotonia Brachycephaly (small head with flat back) Single palmar crease Short neck Short stature Flattened face and nose Prominent epicanthic folds Upwards slopping palpebral fissure
What are the complications of downs syndrome?
1 in 3 have heart problems- particularly ASD, VSD, PDA, teratology of fallot
Recurrent otitis media
Deafness
Eye problems- myopia, strabismus, cataracts
Hypothyroidism
Atlantoaxial instability
Leukaemia is more common in children with Downs
Dementia
What is the combined test for downs syndrome?
This involves blood results combined with ultrasound results
Bloods: PAPPA and Beta HCG
Ultrasound: measuring the nuchal translucency (thickness of the back of the neck of the fetus)
What is the triple test for downs syndrome?
Beta HCG
Serum oestriol
AFP
What is the quadruple test for DOWNs syndrome?
Inhibin A
Beta HCG
PAPPA
AFP
The screening tests for down syndrome show the risk of the mother having down syndrome, over what risk level is the woman offered amniocentesis/ chorionic villus sampling?
When the risk is greater than 1 in 150 (5%)
These tests involve taking a sample of the fetal cells which then undergo karyotyping to give a definitive answer to whether the fetus is affected by Downs or not.
When would you use chorionic villus sampling and when would you use amniocentesis?
. Chorionic villus sampling is used when testing is done in earlier pregnancy (<15 weeks)
. Amniocentesis is done later in pregnancy when there is enough amniotic fluid to make it safer to take a sample
What is the risk of miscarriage for amniocentesis/chorionic villus sampling?
The chance of miscarriage after CVS is 1 in 100
Amniocentesis carried out between the 15th and 20th week and again the same miscarriage chance
What is a new method thats being used instead of chorionic villus sampling/amniocentesis?
Non invasive prenatal testing
What is the management of down syndrome?
Management will involve members of a MDT Occupational therapy Speech and language therapy Physiotherapy Dietitian
Some routine follow ups are important for children with downs syndrome? Eye checks Hearing checks (audiometry) Regular thyroid checks (2 yearly) Echocardiogram to detect cardiac defects Etc etc
What is kleinfelter syndrome?
This is when a male has an additional X chromosome.
Rarely males can have more than one additional X chromosome
What are the features of klinefelter syndrome?
Usually patients will appear as normal males until puberty
At puberty they may develop features suggestive of their condition…
. Taller height . Wider hips . Gynaecomastia . Weaker muscles . Small testicles . Reduced libido . Shyness . Infertility . Subtle learning difficulties
What are the management options of Klinefelter syndrome?
Testosterone injections
Advanced IVF techniques have the ability to allow fertility
Breast reduction surgery for cosmetic purposes
MDT input: speech and language, occupational therapy, physiotherapy, educational support for dyslexia and other learning difficulties.
What are the complications of klinefelter syndrome?
Breast cancer (compared with other males but still less than females)
Osteoporosis
Diabetes
Anxiety and depression
What is turners syndrome?
This is where a female has a single X chromosome making them 45XO (the O refers to an empty space where the other chromosome should be).
Cubital valgus is a feature of turners syndrome, What is cubitus valgus?
An abnormal features of the elbow, when the arm is extended downwards with the palms facing forward. The angle of the forearm at the elbow is exaggerated angled away from the body.
What are the features of turners syndrome?
Short stature Webbed neck High arching palate Downward sloping eyes with ptosis Broad chest with widely spaced nipples Cubitus valgus Underdeveloped ovaries with reduced function Late or incomplete puberty Most females are infertile
What are the associated conditions of turners?
Recurrent otitis media Recurrent UTI Coarctation of the aorta Hypothyroidism Hypertension Obesity Diabetes Osteoporosis Various specific learning disabilities
What are the management options for turners syndrome?
. Growth hormone therapy can be used to prevent short stature
. Oestrogen and progesterone replacement to help establish female secondary sex characteristics, regulate menstrual cycle and prevent osteoporosis
. Fertility treatment can increase chances of becoming pregnant
Associated conditions like hypothyroidism and hypertension should be treated appropriately.
What is noonan syndrome?
Genetic condition
Autosomal dominant
Thought to be the male ‘turners’
As well as features similar to turners, what other features would someone with noonan syndrome have?
Pulmonary valve stenosis Ptosis Triangular shaped face Low set ears Coagulation problems: factor XI deficiency
What is marfan syndrome?
Autosomal dominant conditions which affects the gene coding for fibrillin
Fibrillin is an important component of connective tissue, which means that people with Marfans have features resulting from abnormal connective tissue
What are the features of marfan syndrome?
Tall stature Long neck Long limbs Long fingers (arachnodactyly) High arch palate Hypermobility Pectus carniatum/pectus excavatum Downward slopping palpable fissures
What would someone with Marfan syndrome present like in an OSCE?
Tall
Hypermobility
A murmur suggestive of mitral or aortic regurgitation
What are the associated conditions of marfan syndrome?
Lens dislocation in the eye Joint dislocations and pain due to hypermobility Scoliosis of the spine Pneumothorax GORD Mitral valve prolapse (with regurgitation) Aortic valve prolapse (with regurg) Aortic aneurysms
What is the management of marfans syndrome?
The main risks are the cardiac complications, particularly valve prolapse and aortic aneurysms
Where these complications occur they may require surgical correction
Also you can minimise the cardiovascular risk to minimise blood pressure and heart rate to reduce stress on heart and other complications occuring
Physiotherapy
Yearly opthalmologist and echocardiograms
What is fragile X syndrome?
This is caused by a mutation in the FMR1 (fragile X mental retardation 1) gene on the X chromosome. The FMR1 gene codes for fragile X mental retardation protein which plays a role in cognitive development of the brain.
What are the clinical features of fragile X syndrome?
Delay in speech and language development Intellectual disability Long, narrow face Large ears Large testicles after puberty Hypermobile joints ADHD Autism Seizures
What is the treatment of fragile X syndrome?
No cure for the condition
Supportive and involves treating the symptoms
Involves MDT
