PCKD

Question 1

Polycystic Kidney Disease

Answer 1

1. genetic d/o where abnormal cysts develop and grow in kidneys
2. multi-system d/o where cysts occur in liver, seminal vesicles, pancreas, and arachnoid membrane
   - vascular anomalies, intracranial aneurysms + aortic dilation and mitral valve prolapse

Question 2

Risks with PCKD

Answer 2

1. intracranial aneurysm
2. aortic dilation
3. mitral valve prolapse

Question 3

Genetics PCKD

Answer 3

1. Autosomal Dominant
2. mutation in PKD 1 & 2 genes
3. expression of other organ system manifestations is the same with all mutations (genetic heterogeneity)
4. approx 5% de novo mutation

Question 4

PKD 1 & 2 gene mutation

Answer 4

form protein complexes in primary cilia of renal tubules, cardiac myocytes, myofibroblasts of heart valves and vessels

Question 5

PKD1 mutation

Answer 5

1. chromosome 16
2. 85% mutations
3. cause autosomal recessive polycyclic kidney disease (unknown function)
4. more severe clinical symptoms, earlier onset

Question 6

PKD2 mutation

Answer 6

1. chromosome 4
2. 15% all mutations
3. less severe, later onset than PKD1

Question 7

normal function PDK 1 & 2

Answer 7

1. help regulate growth, division, cell movement, and interactions with other cells

Question 8

environmental factors affecting penetrance

Answer 8

1. hypertension before age 35
2. hematuria before age 3
3. hyperlipidemia at any age
4. coexistence sickle cell trait

Question 9

Factors influencing penetration

Answer 9

1. genetic modifiers: inherited genes that alter expression of mutation genes
   - ex. sickle cell trait
2. homozygous expression=spontaneous abortion
3. highest penetrance in PKd1 mutations
4. anticipation: prediction of worsening disease due to increased in number of repeating units of defective gene
   - -triplet repeat expansion

Question 10

anticipation

Answer 10

prediction of worsening disease due to the increase in the number of repeating units of defective gene
-triplet mutation

Question 11

Dx adults with no family hx PCKD

Answer 11

1. at least 2 bi/unilateral cysts in < 30 yrs old
2. 2 cysts in each kidney in individuals 30-39yrs
3. 4 cysts in each kidney in individuals > 60 yrs old

Question 12

dx adults with family hx PCKD

Answer 12

1. enlarged kidneys and liver noted on PE
2. hypertension
3. mitral valve prolapse
4. abdominal wall hernia

Question 13

Children Dx PCKD

Answer 13

1. large echogenic kidneys without distinct macroscopic cysts

Question 14

PCKD genetic testing and counseling

Answer 14

1. testing available for family members of patients with documented mutations
   - including prenatal testing
2. testing indicated for relatives of proband in end stage renal disease when screening relative for living-donor kidney transplant
3. genetic counseling indicated for affected individuals AND those at risk for PCKD due to positive family hx

Question 15

Management PCKD

Answer 15

depends in disease manifestations at diagnosis

1. lifestyle mod and pharma to treat hypertension
2. renal protective drugs
   - angiotension-converting enzyme ACE inhibitor
   - angiotension II receptor blockers ARBC
3. decrease dietary proteins
4. pain management