Genetic diseases

Question 1

What is FAP?

Answer 1

Familial adenomatous polyposis

Autosomal dominant genetic disease due to mutation in APC gene leading to proliferation of adenomatous polyps in the gastrointestinal tract

Question 2

What is APC? Where is the gene located?

Answer 2

Adenomatous Polyposis Coli is a tumor suppressor gene located at chromosome 5q21-q22

Question 3

What is the pattern of inheritance of FAP? What is the penetrance?

Answer 3

Pattern of inheritance: autosomal dominant
Penetrance: complete penetrance for colonic manifestations, variable penetrance for extracolonic manifestations

Question 4

What types of FAP and their characteristics?

Answer 4

Classic: profuse polyposis ranging from 100-1000s

Attenuated: 10-100s, diagnosed later, more proximal distribution

Question 5

What are the extracolonic manifestations of FAP?

Answer 5

• Gastric polyps
• Duodenal adenomas
• Desmoid tumors
• Benign thyroid nodules
• Hepatoblastoma
• Medulloblastoma
• Adrenal tumors

Question 6

Gardner syndrome

Answer 6

used to describe families with colonic polyposis and extracolonic manifestations

interchangeable term with FAP

Question 7

Turcot syndrome

Answer 7

brain tumor - polyposis syndrome

mainly medulloblastoma and glioma

Question 8

Surveillance for classic FAP

Answer 8

• Yearly colonoscopy from age 10-15
• Elective colectomy
• OGD every 6-12 months
• USG thyroid from late teens, repeat every 2-5 years

Question 9

Types of elective colectomy for FAP

Answer 9

• Total proctocolectomy + end ileostomy
• Total proctocolectomy + IRA
• Total protocolectomy + IPAA

Question 10

What is risk for developing colorectal cancer in FAP patients?

Answer 10

100%

Question 11

What is HNPCC?

Answer 11

Hereditary Non-polyposis Colorectal Cancer is a hereditary syndrome of colorectal cancer. It is associated with early onset CRC due to a mutation in DNA mismatch repair gene leading to rapid adenoma-carcinoma sequence

Question 12

What is the genetic traits of HNPCC

Answer 12

Autosomal dominant

70-80% Penetrance

Question 13

What is the Amsterdam criteria?

Answer 13

• More than 3 members with colorectal or extra-colonic cancer
• More than 2 generations involved
• 1 affected case is first degree relative of others
• More than 1 diagnosed before age of 50
• Excluded FAP

Question 14

What is the management of HNPCC patients?

Answer 14

• Genetic counseling
• Colonoscopy every 1-2 years starting at 25
• Annual colonoscopy at 40 years old
• Gynae: vaginal exam + endometrial aspirate every 3 years from 25, transvaginal/abdominal USG form age 35 every 2 years
• Urological: urine cytology and USG kidney/bladder from 25 onward every 3 years
• OGD (if positive family history) every 2-4 years at age 30 onwards

Question 15

What are Lynch associated cancers?

Answer 15

• GI: Gastric, Small bowel
• Gynae: Endometrial and Ovarian
• Selective: Urinary tract and Pancreatic
• Skin cancer