Cardiovascular disorders Flashcards
Brugada
Inheritance: Autosomal dominant
Genes: SCN5A, SCN1B, SCN2B, SCN3B, GPD1L, CACNA1C, CACNB2, CACNA2D1, KCND3, KCNE3, KCNE1L (KCNE5), KCNJ8, HCN4, RANGRF, SLMAP, and TRPM4
Major features:
●Sudden death-Mean age ~40 years
●Abnormal ECG
oNegative T wave, coved type ST segment
●Ventricular fibrillation
●Self-terminating polymorphic ventricular tachycardia
●Episodes of syncope
●Nocturnal agonal respiration (gasping)
CACNA1C also associated with Timothy Syndrome
Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)
●Type of Arrhythmia
●Sudden death or syncope with exercise/excitement
●Hard to distinguish from LQTS when sudden death is the presenting symptom, however CPVT is associated with normal baseline/resting ECG and abnormal ECG only after andrenergic event
●Major cause of sudden death in childhood
Cerebral Autosomal Dominant Atteriopathy with Subcortical Infarcts and Leukoencephalopathy (CAUDASIL)
Inheritance: Autosomal dominant Genes: NOTCH3 ●Migraines with aura ●Strokes ●Mood disturbances ●Progression to subcortical dementia ●Pseudobulbar palsy ●Leukoencephalopathy ●Onset usually between 35-55 yo Most common form of hereditary stroke disorder
Familial Hypercholesterolemia
Inheritance: Autosomal dominant, autosomal recessive
Genes: LDLR, APOB, PCSK9, LDLRAP1
Major features: ●Xanthomas – cholesterol-rich fat deposits beneath the skin around the eyes and tendons ●Elevated cholesterol ●Premature atherosclerosis ●Coronary artery disease ●Increased risk for MI
Homozygotes have more severe features and may require liver transplant/suffer MI much earlier
oLiver transplant is only for severe cases, but the major source of the problem/defective enzymes are in the liver, so this effectively treats the disease (however, risks for organ transplantation
Hereditary Hemorrahgic Telengiectasia
Inheritance: Autosomal dominant
Genes: ACVRL (ALK1, ENG, SMAD4, GDF2
●Telangiectasias (blood vessel malformations)
oMucosal lining of the nose, lips/tongue, gastrointestinal tract
●Epistaxis (nose bleeds)
●Arteriovenous malformations (AVMs) (occur in large organs)
oIn lung, brain, heart, GI/liver may all cause lethal stroke/MI/cardiac failure
●Juvenile polyps (SMAD4 only)
SMAD4 is also a Juvenile Polyposis/Cancer gene!!! (SEE HEREDITARY CANCER SYNDROMES)
Long QT syndrome
Inheritance: Autosomal dominant, autosomal recessive
Genes: A lot
Major features:
●Prolonged QTc interval on ECG
o“Torsades de pointes” characteristic finding (generates from left ventricle)
●Sudden death, especially in andrenergic states (excitement, exercise, emotion)
●Syncope
Jervell and Lange-Nielsen syndrome
Inheritance: AR
Genes:KCNE1, KCNQ1
LQTS with congenital deafness
Timothy syndrome
Inheritnace: AD ●LQTS ●Syndactyly ●Autism ●Structural cardiac malformations ●ID ●Dental anomalies
SHORT QT syndrome is clinically indistinguishable from LQTS, but much rarer, and can be distinguished through ECG findings (shortened QTc vs elongated)
Cardiomyopathies
- Hypertrophic (HCM)
- Dilated (DCM)
- Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy
- Left-Ventricular Non-compaction (LVNC)
HCM
Hypertrophy, typically of the left ventricle, which leads to reduced cardiac output
●Caused by mutations in sarcomeric genes
●Seen in Noonan, Fabry, etc
Dilated Cardiomyopathy (DCM)
Stretching of muscle fibers (often in LV) leads to dilation of the chamber and reduced cardiac output
●Caused by mutations in cytoskeletal genes
●Seen in DMD, mitochondrial diseases
ARVD/ARVC
Caused by fibrofatty replacement of the right-ventricular heart tissue (myocardium)
●Associated arrhythmia generated from the right ventricle
●In recessive form can be seen with palmoplantar keratoderma and “wooly hair” (Naxos/Carvajal Disease)
●Caused by mutations in desmosomal genes
LVNC
During embryogenesis the heart is made up of spondy layers of blood vessels, which should normally compact. Failure to compact leads to LVNC
●Excessive, prominent, persistent trabeculations are major feature
●Even though it is congenital, typically manifests later in life
