Arrhythmias, Cholesterol, & Dyslipidemias

Question 1

What genes are associated with Long QT Syndrome?

Answer 1

KCNQ1, KCNH2, SCN5A (GoF), CACNA1C (GoF), CALM1,
CALM2, CALM3, CAV3, KACNJ2, TRDN, KCNE1, KCNE2

Question 2

What are other conditions associated with Long QT Syndrome?

Answer 2

Andersen-Tawil syndrome
■ AD (KCNJ2) includes muscle weakness, episodic paralysis,
facial dysmorphism, dental abnormalities, small hands/feet

○ Jervell and Lange-Nielsen syndrome
■ AR (KCNQ1, KCNE1), associated with congenital hearing loss

○ Timothy syndrome
■ AD (CACNA1C), hand/feet syndactyly, ASD/ID, characteristic
facial features

Question 3

What genes are associated with Short QT Syndrome?

Answer 3

KCNH2 (GoF), KCNQ1 (GoF), KCNJ1 (GoF), CACNA1C
(LoF), CACNB2 (LoF), CACNA2D1 (LoF)

Question 4

What genes are associated with Brugada Syndrome?

Answer 4

SCN5A (LoF) in 30% of cases, 65% unknown
○ GPD1L, CACNA1C, CACNB2, SCN1B, KCNE3, SCN3B, HCN4, KCND3

Question 5

What is Brugada Syndrome?

Answer 5

Characteristic abnormality of the ST segment
○ May have other conduction abnormalities: first degree heart
block, sick sinus syndrome, bundle branch block, others

○ Triggers include: heat exhaustion, dehydration, sodium channel
blockers, lithium, tricyclic antidepressants, alcohol, cocaine,
marijuana

Patients may have history of recurrent syncope, ventricular
fibrillations, ventricular tachycardia, cardiac arrest

Question 6

What is Catecholaminergic polymorphic ventricular tachycardia
(CPVT)?

Answer 6

Exercise- or emotion-induced polymorphic or bidirectional or
ventricular tachycardia
○ Syncope, palpitations, or dizziness during exercise or
heightened emotion
■ Typically first presenting between age 7 to 12 y/o
■ Cardiac death may be triggered by similar events
○ Ventricular fibrillation in times of acute stress
○ EKG otherwise normal

Question 7

What genes are associated with CPVT?

Answer 7

○ AD: RYR2 (GoF), CALM1, CALM2, CALM3, CASQ2, KCNJ2
○ AR: TECRL, TRDN

■ CASQ2-heterozygotes may have symptoms, more typical
presentation for homozygotes

○ Atypical CPVT may be observed for individuals with mutations
in CALM1, CALM2, CALM3, CASQ2, KCNJ2, TECRL, and TRDN

Question 8

What other conditions are associated with CPVT?

Answer 8

RYR2 mutations or large deletions have also been associated
with non-typical HCM or LVNC, with or without CPVT

Question 9

What is early-onset Afib?

Answer 9

Irregular heart rhythm, rate may be controlled or uncontrolled
○ Increased risk for heart failure or stroke
○ Common in the general population
● Patients may have history of palpitations, lightheadedness, fatigue,
shortness of breath, chest pain
○ Diagnosis under the age of 60 = “early onset”
■ Under 45 y/o?
○ May be impacted by lifestyle: smoking, alcohol, obesity,
ancestry, hypertension, etc.

Question 10

What genes are associated with early-onset Afib?

Answer 10

Candidate genes according to one article: SCN5A, KCNA5, TTN, PITX2,
KCNQ1, GJA5, LMNA, TBX5, NPPA, NKX2.5, GATA4, GATA6
○ Potentially a precursor to cardiomyopathy diagnosis
○ ∼4%–11% yield of genetic testing for individuals with EOAF
● Still investigating association, no clear management without known
genetic cause at this point
○ If pathogenic variants identified, follow published guidelines
according that gene and associated conditions