Genetics Flashcards
How is Down’s syndrome screened for?
- Nuchal Translucency (skin fold thickness behind neck)
- Blood serum markers in mother
Why is the nuchal translucency increased in babies with Down’s Syndrome?
- indication that lymphatics are developing too slowly
=> gap is too large
How is invasive genetic testing done whilst the foetus is in utero?
- need to test tissue with same genetic makeup as the baby
i. e. chorionic villus sampling of placenta OR amniocentesis
When can chorionic villus sampling and amniocentesis take place?
CVS - 11.5 weeks
Amniocentesis - 15 weeks
What is Non Invasive Prenatal Testing?
Taking mothers blood and testing for free foetal DNA
- this can get into mothers circulation via placenta
What can non-invasive prenatal testing look for?
- sex of baby
- trisomy
OCCASIONALLY
- chromosome deletions
- single gene transfers
What is meant by confined placental mosaicism?
- trophoblasts divide quickly => develop more abnormalities than cells that go on to become blastocyst
=> Placenta may have chromosome abnormalities that the baby does NOT have
If NT, serum markers in the mothers blood and NIPT indicate a high risk of Trisomy 21, what is the percenatge risk of the baby having this condition?
99%+
How do geneticists test mothers blood in NIPT and confirm a high suspicion of trisomy 21?
- count number of each chromosome i.e. 1,2,3 etc
- Count number of chromosome 21
=> if out of proportion to number of other chromosomes, this would indicate T21
NIPT can also be used for what other genetic conditions?
T18 (Edward’s)
T13 (Patau’s)
Also Turners 45X and Kleinfelters 47XXY
What does NIPT reduce the risk of?
Miscarriage due to amniocentesis
Describe the appearance of a baby with Down’s Syndrome ?
- short fingers
- round face
- large tongue
- epicanthic folds
What are the benefits of an antenatal genetic screening test?
- identify and treat early
- identify if other family members are at risk
Why is there a debate surrounding screening for Down’s Syndrome in pregnancy?
- there is not additional benefit to treating early
- HOWEVER people do say that early termination option for mother may be a benefit to the child
Up to what gestation can a mother choose to terminate her baby who is at risk of down’s syndrome?
NO LIMIT
- if risk of serious abnormality to child or to health of the mother
WHat is anencephaly, and why is early diagnosis significant?
- no brain/head development
- baby MAY progress to full term (may be stillborn due to labour)
- parents need to psychologically prepare for appearance and limited survival of baby
If a family do not wish to proceed with a termination after a difficult genetic diagnosis in their baby, what other option do they have?
- carry baby to term
- organ donation
How does a baby with T18 (Edward’s) appear, and how long do babies with this condition survive?
- small baby with smal facial features
- life limited => many don’t survive for long after birth (virtually none within 1 year)
Is Down’s Syndrome considered a “severe” genetic disease?
- Not necessarily due to variable presentation
- parents may not be equipped do deal with any of these
They can have:
- cardiovascular disease
- behaviour issues
- low IQ requiring lots of support
- multiple surgeries -> time in ICU
- increased incidence of some cancers
If a US scan indicates a hand abnormality, what must you be aware of?
- is this part of another condition/syndrome?
- e.g. DiGeorge, Thrombocytopaenic Absent Radius etc
What criteria do patients make a Termination of Pregnancy decision upon?
- social/religious views
- previous experience
- perception of disease
What is NIPT eventually going to be able to analyse?
Chromosome Karyotype
What invasive genetic testing is carried out on the chorionic villus sample of on an amniocentesis sample?
- Chromosome Microarray (1st Line)
- Single Gene changes
=> PCR
=> Next Generation Sequencing
What is the problem with chromosome microarray?
Cannot pick up balanced translocations
- only identifies EXTRA or MISSING genetic material
What can Chromosome Microarray be used to identify?
- Trisomy
- Foetal Abnormalities
- Unbalanced Translocations
What is the disadvantage of PCR?
- you need to know where to look within 30,000 genes
- cannot sequence ENTIRE genome
e.g. if baby is thought to display Myasthenia Gravis symptoms, then this is an NMJ problem and all genes encoding for ACh can be tested
Prenatal genetic testing allows the obstetrics team to decide on a high or low risk pathway for a baby’s delivery. TRUE/FALSE?
TRUE
What is meant by a “floppy baby”?
- lack of head control
- low tone
- baby lying flat
- no resistance to movement
- easily moved and fall out of grasp
Where in the nervous system can a lesion cause a floppy baby?
- cortex
- spinal cord
- anterior horn cells/motor neuron
- NMJ
- Muscles
What problems in a baby’s cortex can cause a “floppy baby”?
- Hypoxic Ischaemic Encephalopathy
- Intracranial Haemorrhage
- Cerebral Malformation
- Chromosomal (T21, Prader-Willi)
- Congenital infection (TORCH)
- Acquired Infection
- Peroxisomal disorders
- Drugs (e.g. Benzodiazepines)
What common congenital infections are outlined by the acronym TORCH?
TO - Toxoplasmosis
R - Rubella
C - CMV
H - Herpes, HIV, Hepatitis
What damages the spinal cord and can cause a “floppy baby”?
- Birth trauma (Breech)
- Syringomyelia (cysts in spinal cord - often causes “mermaid” looking baby => legs stuck together)
What conditions due to damage or lesion of the anterior horn cells can cause a baby to appear floppy
Spinal Muscular Atrophy
How would you determine that the cause of “floppy baby” was central rather than peripheral?
- normal strength
- normal or increased reflexes
+/- seizures, dysmorphic features or decreased alertness
What investigations would you consider if a “floppy baby” was presented?
Bloods
- genetic
- metabolic
- congenital infection screen
- Creatinine Kinase (increases if muscle breakdown)
Imaging
- US
- MRI
Neuro
- EEG
- EMG (only after 6 months of age)
What early intervention can be offered if the disease causing “floppy baby” is picked up early?
- Respiratory support (if breathing muscles struggling)
- Feeding Support
- Physio
- OT
- Parental Involvement
If a family history does not highlight a dominant, recessive or X Linked pattern of genetic disease, does this mean that a baby’s condition has no genetic cause?
No
- May be a de novo mutation
Why does consanguinity increase recessiveness of genetic disease?
- people reproducing are from same genetic lineage therefore both are more likely to be carriers
What disorders can be offered rapid testing after a floppy baby is noticed on examination, yet no abnormalities on Chromosome Microarray?
- Myotonic dystrophy
- Spinal Muscular Atrophy
- Prader-Willi Syndrome
What part of the genetic materia is sequenced using next generation sequencing?
- dont need to sequence whole genome
- only sequence exons (2-3%)
- beware of polymorphisms which may not actually cause disease
Give an example of a condition which can cause floppy baby but can now be treated?
Spinal Muscular Atrophy
- genetic treatment is targeted at RNA to modify damaged mRNA
- NNT = 1 or 2 => VERY EFFECTIVE
- However, very expensive!
