channelopathies

Question 1

define channelopathies

Answer 1

• improper function of the heart as a reault of mutations to proteins that make up the ion channels in the heart
• each ion channel can be associated with a channelopathy

Question 2

define cardiomyopathies

Answer 2

physcial change in the structure of the heart muscle due to the inability of the heart to properly pump blood

Question 3

what does the cardiac action potential represent?

Answer 3

represents the total electricity of an individual cardiomyocyte undergoing a contraction (essential)

Question 4

what contributes to the formation of the cardiac action potential? why is this important?

Answer 4

• ion channel composition of each cardiac cell

- important for propogation of excitation

Question 5

what are the major ion channels?

Answer 5

Ca, K, Na

Question 6

how are channelopathies typically diagnosed?

Answer 6

-through the use of ECG recordings (present a map of electrical impulse throughout the heart)

Question 7

what is the pathophysiology of a normal patient compared to one with long QT syndrome?

Answer 7

• normal: arterial depolarization (P wave), ventricular depolarization (QRS complex) and ventricular repolarization (S-T wave)
• LQTS: have a long QT interval (can differ btwn patients)

Question 8

what can LQTS lead to if left untreated?

Answer 8

uncoordinated heart muscle function and fatal cardiac arrythmias

Question 9

what the definitive mutations associated with LQTS?

Answer 9

• KCNQ1 (first & definitive) (LQT1)
• KCNH2 (LQT2)
• SCN5A (LQT3)

Question 10

is clinical lab testing offered for all genes associated with LQTS?

Answer 10

no, only the three w a defenitive connection

Question 11

locus and clinical _____ is associated with LQTS?

explain.

Answer 11

heterogeneity

• locus: each of the channelopathies may be caused by multiple mutations
• clinical: mutations in many of these genes have a role in more than one of these channelopathy subtypes

Question 12

explain LQT1 (mutation and cause of cardiac arythmia)

Answer 12

• mutations occur in the KCNQ1 gene (35%)

- this type causes cardiac arythmias while participating in physcial activity

Question 13

explain LQT2 (mutation and cause of cardiac arythmia)

Answer 13

• mutations occur in the KCNH2 gene (30%)

- this type is most commonly caused by auditory triggers as well as the postpartum period

Question 14

explain LQT3 (mutation and cause of cardiac arythmia)

Answer 14

• mutations occur in the SCN5A gene (10%)

- often die during rest (most often assoicated with sudden infant death syndrome)

Question 15

the younger somone passes away from LQTS suggests:

Answer 15

it was an inherited condition

Question 16

define penetrance

Answer 16

the extent to which an individual will develop some aspect of the disease if they possess a mutation in the disease causing gene

Question 17

define expressivity

Answer 17

the presentation of the disease/the intensity of the phenotype

Question 18

100% penetrance and constant expressivity means

Answer 18

every person with the mutation will display the same symptoms of the channelopathy of interest

Question 19

<100% penetrance and constant expressivity means

Answer 19

not every family member with the mutation will display symptoms associated with the disease but if they do they’ll be the same as all other family members

Question 20

<100% penetrance and variable expressivity means

Answer 20

not every family member with the mutation will display the symptoms and if they do they will show a variety of symptoms throughout the family

Question 21

list factors that could result in variable expressivity

Answer 21

• genetic background
• environmental influences
• lifestyle

Question 22

lower penetrance makes it harder to associate between the disease and the gene, true or false?

Answer 22

true

Question 23

define benign genomic variants

Answer 23

genomic variant that does not increase a patients susceptibility to a disease/disorder

Question 24

define a genomic variant with unknown significance

Answer 24

genomic variant that has an unknown effect on the patients susceptibility to a disease/disorder

Question 25

define a pathogenic genomic variant

Answer 25

genomic variant that is known to increase a patients susceptibility to a disease/disorder

Question 26

is measuring a patients QT length a definitive method for diagnosis LQTS? why or why not?

Answer 26

• no

- research has shown an overlap in QT length between normal non-carriers and LQTS mutation carriers

Question 27

explain LQTS risk stratification

why do we do this?

Answer 27

• can’t just identify mutation and properly diagnose

- patients are risk stratified based on gender, QT interval, type of LQTS, genotype and presence of mutation(s)

Question 28

what are the two primary stategies for treating channelopathies? is treatment of this disease important?

Answer 28

yes bc risk of sudden death

(1) arrythmia prevention
(2) arrythmia termination

Question 29

explain the process of arrythmia prevention.

what are the limitations to this method?

Answer 29

• perscribe beta-blockers
• work to limit adrenergic stimulation that can provoke arrythmia
• limitations = cause fatigue (don’t do exercise), leads to poor compliance (especially in younger ppl)

Question 30

explain the process of arrythmia termination

Answer 30

• implantable cardioverter-defibrillator (ICD) can be used to deliver elctrical shock to the heart
• wires link from heart to device and detect normal rythm
• if arrythmias arise: provides shock to heart to reset
• not always effective but has saved many