Genetics Flashcards
What questions to ask if Haemophilia B
-is the mom symptomatic
What happens to Factor 8 and Factor 9 in pregnancy?
It increases - increases coagulopathy
In which week is the test for Down Syndrome done?
11th week
How do you screen the baby for Down’s syndrome?
Nuchal translucency: Look at the gap btw the neck and the back wall. if the lymphatic development is slow, the gap is too big. ig bigger than 3.6 (it could indicate a change in lymphatic development)
When can amniocentesis be done?
15 weeks
Non-invasive pre-natal testing
Placenta sheds foetal DNA to the maternal circulation - 10% of the serum in the mom’s blood comes from the baby
Confined placental mosiacism
cells that go to make the placenta have an abnormal chromosome make up- because of multiple divisions. Hence CVS can look at mosaics without it the baby actually having it
What are the cons of non-invasice pre-natal testing?
Can have false positives - because of mosaic divisions in placental cells that keep dividing –> can have trisomy 21;
What are the steps in Down’s syndrome screening?
1st - Combined test: US and blood markers in mother (screening)
2nd - High risk –> NIPT lots and lots of counts of each chromosome - marginal over-representation of trisomy 21
+/- Diagnostic –> need to follow it with amniocentesis or no invasive test
What other tests can be done with non-invasice pre-natal screening?
trisomy 18
trisomy 13
Heal break test
Metabolic conditions
Is there much of a difference when screening for Down’s wrt end point in care?
not much of a difference, but atleast it prepares the mother for the scenario
When can you opt for a ToP?
surgical treatment - before 13 weeks
Induction - thereafter
no time limit on TOP if there is a risk of serious abnormality in the child or to the health of the mother
Would you sign a TOP for anencephaly?
Anencephaly - no brain development
Can sign it
When can CVS be done?
11 - 14 weeks
Features of Edwards syndrome
- every cell has a trisomy 18
- Will die before or shortly after birth
- not inherited
Features of mosaic 18
- not all cells have a trisomy 18
- 7/10 babies born with mosaic trisomy will live for at least a year and, in rare cases, may survive into early adulthood
- Severity depends on the number of and type of cells that have the extra chromosome. Some babies may only be mildly affected, while some can be severely disabled.
Would you give a TOP for a patient with hand abnormality?
It can be a part of another syndrome, hence it can be variable:
falcon anaemia
DiGeorge’s syndrome
Thrombocytopaenia
Would you follow up with a baby girl with Haemophilia?
No, write it up to haematology and have a chat when she reaches a child bearing age
What is done in invasive testing?
1st line - Chromosome testing- chromosome microarray
But can’t pick up balanced chromosome abnormalities - just deletions or additions
Pros of Chromosome microarray
high resolution
technologically easier
rapid
Cons of chromosome microarray
- won’t detect balanced chromosomal abnormalities
- also finds polymorphisms - don’t need to report as you don’t know
- may make incidental findings - might have to report it as it might be important for the baby and the mom might have it as well
When do you do a aCGH?
- chromosome trisomy
- foetal abnormality on scanning
- parent has a balanced chromosomal rearrangement
With PCR which part of the genome do you sequence?
the part that you are interested in
What is a floppy baby?
- rag doll
- lack of head control
- increased range of movement
- frog legged
- feel like they’ll fall out of your grasp
- possibly breathing difficulties
- low tone
Causes of low tone:
centrally - cortex, spinal cord, anterior horn cells/ motor neurons
Peripheral - neuromuscular junction
DIfferential diagnosis of low tone:
Central:
- hypoxic ischaemic encephalopathy
- intracranial haemorrhage
- chromosomal abnormality
- congenital infections (TORCH - Toxoplasmosis, Rubella, CMV, Herpes, HIV, Hep)
- acquired infection
- peroxismal disorders
- drug side effects (eg: benzodiazepines)
Spinal cord:
- birth trauma (expecially breech delivery)
- syringomyelia
Anterior Horn Cell:
-spinal muscle dystrophy
Do you do a rubella test now?
No, before AB for Rubella used to be checked
What examination would you do on a floppy baby?
central: - normal strength, normal/ increased DTRs, +/- seizures, +/ dysmoprhic features, reduced alertness
Anterior horn cell: generalised weakness, decreased/ absent DTRs, fasciculations, often described as alert
NM Junction -weakness, face/eyes/bulbnar -normal DTRs -no fasiculations \+/- arthrogryposis contractures
Muscle
- weakness, proximal >distal, face, EOM
- decreased DTRs
Nerve
-weakness distal>proximal
-decreased/ absent DTRs
+/- fasiculations
What steps will be done next after floppy baby?
Bloods - genetics, metabolic, congenital infection screening, CK (duchennes)
Neurology review (EEG/ EMG after 6 months)
Imaging:
cranial USS
MRI
If no family history or no result on microarray, does it mean that there is no abnormality?
No, can have a de novo mutation as well!
can do a NGS (next generation sequencing)
How many cranial nerves can you test on a neonate?
Everything except smell
Anterior horn cell dysfunction causes which disease?
spinomuscular atrophy
Prader-Willi syndrome
hypotonic
Which test would you do most rapidly?
- Myotonic dystrophy
- spinal muscular atrophy
- prader-willi syndrome
Spinal muscular atrophy Type 1
very expensive management
severe disease
