Cardiovascular genetics Flashcards
What are cardiomyopathies
a heterogeneous group of diseases of the myocardium associated with mechanical and/or electrical dysfunction
- usually exhibit inappropriate ventricular hypertrophy or dilation
- due to a variety of causes that frequently are genetic
- can be confined to the heart or are part of generalized systemic disorders
Hypertrophic cardiomyopathy genetics
More prevalent in African americans than Caucasians, more prevalent in males than females
Autosomal dependent with incomplete, age-dependent penetrance (do Novo possible in 1/3)
lots of genetic and molecular heterogeneity
Fabry Disease: HCM
Full disorder is X-linked, females rarely affected, and phenotype INCLUDES HCM
HCM-only phenotype: men and women affected equally, presents after 3rd decade
Congenital Long QT syndromes: AD vs AR
AD: prolonged QT interval and sudden death, normal hearing
AR: Prolonged QT and sudden death
congenital deafness
Long QT syndrome types
LQTS1 - 30-35% - physical exercise
LQTS2 - 25-40% -auditory stimuli
LQTS3 - 5-10% - sleep or rest
NOTE: Long QT on EKG is an imperfect biomarker, but the longer the QTc is, the more likely a cardiac evemt
Long-QT syndrome genotype-specific therapy
theoretically possible, unproven efficacy
Drugs: Na+ channel blockers, K+ infusion, K+ channel opener
Brugada syndrome
ST elevation in right precordial leads
Life-threatening ventricular arrhythmias
AD inheritance
No good treatment at this time except defibrillator
Sudden Unexpected Death syndrome
ECG pattern identical to Brugada syndrome
overlap with LQTS3
Brugada syndrome variants and treatment
SCN5A patogenic variant - haploinsufficiency, abnormally fast inactivation
Sodium channel blockers
