TMC 10 Flashcards
Describe the key symptoms of familial hypertrophic cardiomyopathy
Common cause of sudden cardiac arrest in young people killing 5-10% of the affected
Autosomal dominant
Symptoms: Chest pain, dizziness, shortness of breath, fainting, serious arrythmias
Describe the FHCM phenotype
Hypertrophy in cardiac muscle
Blocks blood flow in ventricles
May affect mitral valve causing regurgitation
List the main defective genes that can cause familial hypertrophy cardiomyopathy
Change of an amino acid in the myosin protein
Missense mutation in MYH7 gene
Mutations in myosin mainly
Mutations in troponin T, Troponin I, alpha-tropomyosin and alpha actin
Describe the key symptoms of Malignant Hyperthermia.
Pharmacogenetic disorder where individuals have a reaction to anaesthetics such as halothane and sevoflurane
Describe the Malignant Hyperthermia Phenotype.
Rapid increase in body temperature and metabolism accompanied by contracture of skeletal muscle
Increased tachycardia and increased CO2 production
Acidosis
What gene is associated with Malignant Hyperthermia and how does this cause the condition?
RYR1 channel is defective in the presence of halogenic anaesthetics
Makes the channel leaky
Calcium leaks out of the SR onto the myofibril causing increased contracture consuming ATP and generating heat
Metabolism increases as calcium leaks out
Describe the key symptoms of Central Core Disease and its phenotype.
Non-progressive muscle weakness disorder
Individuals have difficulty climbing stairs, delayed motor milestones and have central cores (amorphous areas) in their skeletal muscle tissue
Typically have malignant hyperthermia as well
What gene is defective in CCD and how does a defect in this gene cause CCD?
Mutations in their RYR1 gene
Leaks in RYR1 calcium release channel
Lower concentration of calcium in SR
Higher resting level of calcium in myoplasm
Some mutations affect coupling between the DHPR and the RYR1
Describe the key symptoms of Catecholaminergic polymorphic ventricular tachycardia (CPVT) and arrhythmogenic right ventricular cardiomyopathy (ARVC).
CPVT - Changes in structure of the mutated RYR2 channel disrupt the careful control of calcium ion flow in myocytes. This triggers abnormal heart rhythm
ARVC - Condition causes part of the heart muscle to break down over time, which increases the risk of arrhythmia and sudden death
What gene is defective in ARVC and CPVT?
RYR2 gene
Describe the key symptoms of Brody’s Disease and the Brody’s Disease phenotype
Muscle cramping and stiffening after exercise or strenuous activity, especially in cold temperatures
Symptoms begin in childhood, usually painless but in some cases can cause mild discomfort
Most commonly affected muscles are arms, legs, and face especially eyelids
What gene is defective in Brody’s Disease and
how does a defect in this gene cause Brody’s Disease?
Mutations in the SERCA gene
Which causes an increased [Ca++]
Describe the key symptoms of Hypokalaemic periodic paralysis (HOKPP) and the HOKPP phenotype
Attacks of muscle weakness or loss of muscle movement that come and go
Episodes of muscle weakness usually last between a few hours and a day
What gene is defective in HOKPP
and how does a defect in this gene cause HOKPP.
CACNL1A3 is defective encoding one of the subunits of the DHPR
Defective in sensing depolarisation so it cannot activate the ryanodine receptor efficiently
