Monogenic disorders

Question 1

What is Huntington Disease and how is it inherited?

Answer 1

Its a neurodegenerative disease due to mutation on the HTT gene, CAG triplet repeat expansion. Autosomal dominant

Question 2

What is the usual age of onset for Huntingtons and what are 5 symptoms?

Answer 2

30-50 years old. Chorea (involuntary movements), paranoia/depression/mood disorders, dementia, slurred speech, unsteady gait

Question 3

How long is the protein that HTT codes for? What does the Huntingtin protein do?

Answer 3

350 kDa. The exact role of HTT protein is unknown but it is related to neuron differentiation/proliferation thus affecting brain development/function

Question 4

How is Huntingtons inherited

Answer 4

Autosomal Dominant

Question 5

Heart cycle - what is S1 and S2 caused by?

Answer 5

S1 is caused by the closure of atriventricular valves and S2 is caused by the closure of semilunar valves

Question 6

What is systole and diastole?

Answer 6

Systole = contraction and Diastole = relaxation

Question 7

What is Long QT syndrome (LQTS)? What does it cause?

Answer 7

A life-threatening cardiac arrythmia due to the prolongation of the QT interval. It causes occurences of cardiac arrest and syncope.

Question 8

What is the leading cause of death in the young?

Answer 8

LQTS. Symptomatic patients without treatment have a mortality rate of 21% within 1 year of the first event

Question 9

What is the molecular mechanism of LQTS?

Answer 9

Muations of potassium voltage-gated channels Q1 and H2. Loss of function on these genes delay ventricular repolarization thus lengthening QT interval

Question 10

What are the two forms of LQT1

Answer 10

Romano ward syndrome AD or Jervell and Lange-Niesen AR w/ congenital deafness

Question 11

LQT2 is caused by mutation of which channel?

Answer 11

KCNH2- Potassium voltage regulated channel 2

Question 12

Why is LQTS dangerous when heart rate is increased?

Answer 12

The QT interval remains longer than needed causing irregular heartbeats.

Question 13

Arrhythmia - Swimming and exertion-induced cardiac events are strongly associated with which LQT?

Answer 13

LQT1

Question 14

How can you treat arrhythmia?

Answer 14

Beta-blockers to block the shortening of the heart cycle cause by adrenaline, which can also lead to arrhythmia

Question 15

What is affected in Marfan syndrome? And mutation on what gene causes it? How is it inherited?

Answer 15

Disorder of the connective tissue due to mutation on FBN1 fibrillin type 1 gene. Inherited as Autosomal dominant

Question 16

What are some Ghent criteria for Marfan syndrome?

Answer 16

Thumb sign, wrist sign, pectus deformity, lens subluxation (ectopia lentis) and, dilation of ascending aorta.

Question 17

How do you diagnose someone without family historiy of Marfan?

Answer 17

Aortic root dilation + ectopia lentis / athogenic FBN1 mutation / Systemic Score greater than or equal to 7 or ectopia lentis with pathgenic FBN1 mutation with known aortic root diameter