L6 - SIDs

Question 1

what does SIDS stand for?

Answer 1

sudden infant death syndrome

Question 2

how is SIDS defined?

Answer 2

The death of an infant which unexpected by previous family history and post mortem fails to find an adequate cause of death

-occurs in children under 1 year of age during sleep

Question 3

how many deaths are caused by SIDS?

Answer 3

2500 deaths a year in the US

-3rd most common cause of infant death

Question 4

what are the risk factors for SIDS?

Answer 4

• male
• 2-4 months old
• viral infection
• prone position (on tummy)
• premature
• winter
• low birth weight
• low socioeconomic/low educational background
• drugs/smoke exposure
• overheating

Question 5

what did the back to sleep campaign acheive?

Answer 5

• encouraged sleeping on backs (less babies sleeping on tummies) - small reduction in the number of SIDS cases

Question 6

what could be the possible causes of SIDS?

Answer 6

• immunological polymorphism - altered inflammatory response
• cardiac ion channel mutation
• autonomic disorders - NT changes
• metabolic disorders - abnormality in liver

Question 7

what was norweigan study which investigated SIDS?

Answer 7

investigated ~34000 babies

• 34 deaths (24 deaths caused by SIDS)
• SIDS had a longer QTc interval but no major differences in HR

Question 8

what QTc interval was above the noraml range in babies according ot norwiegan study?

Answer 8

above 440ms was classed as LQTc

- many SIDS babies had a QTc interval above 440ms - out of normal range

Question 9

what genes were found to be mutated in SIDS babies?

Answer 9

SCN5A (sodium channels), KCNQ1, , KCNE2, KCNJ8

• same genes that are commonly mutated in LQT syndrome

Question 10

what was studied between SCN5A and LQT?

Answer 10

• 201 SIDS cases studied
• 8 mutations studied in SCN5A - spread throughout protein
• no big change in channel function when mutants are overexpressed - may be other risk factors involved which cause death

-F14861, F2004L have slower inactivation - prolong QT interval

Question 11

what causes persistent Na currents?

Answer 11

• cellular acidosis
• depolarising shift - more positive potential required to cause inactivation - delay in inactivation
• Na channels stay open for too long

Question 12

what gene encodes Kir6.1 channel?

Answer 12

KCNJ8

Question 13

what is the Kir6.1 channel?

Answer 13

An inwardly rectifying potassium channel - ATP sensitive channel - metabolic sensor found in the heart
- some SIDS cases have mutation in Kir6.1 channel

Question 14

What happens when the KCNJ8 gene is mutated?

Answer 14

• loss of function mutation in Kir6.1 channels
• current 1/3 less of what it should be from Kir6.1 - repolarisation is delayed as outward rate of Kir6.1 is less then it should be - LQT

Question 15

What is hypoxia associated with in babies?

Answer 15

• premature infants (lungs underdeveloped)
• smoke exposure
• prone position - ribcage cannot filly expnd
• mild viral infection

Question 16

what normally happens to HR and QT after birth - in study in mice?

Answer 16

• HR goes up with age
• ## QT gets shorter after birth to help to increase heart rate

Question 17

What does hypoxia do in baby mice?

Answer 17

• hypoxia decreases heart rate
• hypoxia increases the QT interval
• combine hypoxia with risk factors and cardiac ion channel mutations - increase LQT interval even more - results in death (SIDS)

Question 18

What happens when mice were exposed to hypoxic conditions straight after birth?

Answer 18

60% of the mice die
- longer they had normal oxygen conditions at birth the more likely they were to survive when exposed to hypoxic conditions later on.

Question 19

what effect does hypoxia have on ion channels?

Answer 19

• changes the expression of ion channels
• downregulates ion channels
  e. g. KCN channels downregulated - slower repolarisation rate - LQT