Case 1: FAP Flashcards
What is dyspnea?
shortness of breath
palpitations
can equal “beating out of chest”
is 3 months chronic?
yes
C/C: Fatigue that is affecting acitivities of daily living (ADL), dizziness, exacerbaed by positional change, dyspnea, palpitation, chronic
Differential
CV- CHF, Coronary Arrtery Disease
Endocrine- Hypothyroid
GI - Crohn’s, IBS, Malabsorption, Colon
Cancer
Hematologic- Anemia, cancer related
Psychiatric- Depression, substance-abuse related, chronic fatigue syndrome,
Sleep disordr
MEdication Disordder
What is Gardner syndrome
autosomal dominant with numerous ademaous polyps like FAP, but comes with OSTEOMAS AND OTHER SOFT TISSUE TUMORS
What is Turcot Syndrome
autosomal dominant and has multiple polyps but comes with CNS TUMORS
What is Peutz-Jeghers Syndrome
autosomal dominant and has HAMARTOMATOUS POLYPS (benignt) of GI tract, but increased probabilty of ADENOCARCINOMA of the GI
MELANOTIC ACCUMULATION IN THE MOUTH, LIPS, HANDS AND GENITLA
How is FAP inherited
Autosomal Dominant manner and highly penetrant
What is the utation in FAP
adenomatous polyposis coli, APC
what chromosome is mutated?
APC gene. Chromosome 5q are the cause of
How many exons does this gene have?
15 exons
What does the somatic mutation of APC gene cause
early events in teh majority of sporadic colorectal cancer and adenomas
What are mutations in the middle of the gene (codons 1250-1464) ass. with>
profuse polyposis (>1000 polyps)
What is an extracolonic manifestion
Thyroid cancer
Why doesn’t site of mutation in APC gene not accurately predit a pheontype ?
b/c of additional factors, sucha s modfieir genes
What is the % of successful detection of APC mutation in patients who have classic FAP?
80-90%
What do most mutations in the APC gene lead to?
protein truncation and protein-truncation assay was OG used to deterct altered protien products using RNA and DNA from peripheral blood lymphs
Where is the non-truncating missense mutation ?
caused by a single nucleotide subsittuion in teh genet at 5qI1307K, in approx 6^ Ashkenazi Jews
What does the variant in Ashkenazi jews lead to
carriers 10-15% in carriers
Affected parents have what % chance of passing?
50% chance of passign the APC mutation to their children
Do de novo mutations have risk of inhertince to progeny?
no
11-20% with de novo have somatic mosaicism of APC mutaiton
where is mosaism identified/
in somatic tissue cells but not in periphearl lymphs
phenotype is less severe
what is the incidence of FAP?
2/ million
what is the prevalnace of FAP?
4/ million
what is the estimated lifteime risk of FAP?
1 / 8,000 to 15,000 births
Does FAP affect both sex equally?
YES
What is the treatment for APC mutation at age 10-12; ad families with clinical diagnosis of FAP but no Identified APC mutaiton
annual flexible sigmoidoscopy
Is the risk for duodenal polyposis and carcinoma high in FAP?
yes, therefore it is recommended taht pateitns with AP undergo intial endoscorpy around 20 years old
Screening dependent upon the severity of duondenal polyposis
Prophylactic surgery for the prevention of the colorectal cancer in pateints who have FAP i when?
either at diagnosis or before 25 years of age
What are the three main surgical otpions include?
- Total proctocolectomy (TPC) with permanent ileostomy
- Subtotal colectomy with ileorectal anastomosis,
- Proctocolectomy with ilean pouch-anal anastomosis
What provides the lowest risk of GI cancer and has the lowest risk for compliceation>
TPC + ileostomy
NOt the first choice for patietn who have FAP b/c of disadvantages ass. witha perment ileostomy
Affected parents have what % chance of passing?
50% chance of passign the APC mutation to their children
Do de novo mutations have risk of inhertince to progeny?
no
11-20% with de novo have somatic mosaicism of APC mutaiton
where is mosaism identified/
in somatic tissue cells but not in periphearl lymphs
phenotype is less severe
what is the incidence of FAP?
2/ million
what is the prevalnace of FAP?
4/ million
what is the estimated lifteime risk of FAP?
1 in 8,000 to 15,000 births
Does FAP affect both sex equally?
YES
What is the treatment for APC mutation at age 10-12; ad families with clinical diagnosis of FAP but no Identified APC mutaiton
annual flexible sigmoidoscopy
Is the risk for duodenal polyposis and carcinoma high in FAP?
yes, therefore it is recommended taht pateitns with AP undergo intial endoscorpy around 20 years old
Screenign dependent upon the severity of duondenal polyposis
Prophylactic surgery for the prevention of the colorectal cancer in pateints who have FAP i when?
either at diagnosis or before 25 years of age
What are the three main surgical otpions include?
- Total proctocolectomy (TPC) with permanent ileostomy
- Subtotal colectomy with ileorectal anastomosis,
- Proctocolectomy with ilean pouch-anal anastomosis
What provides the lowest risk of GI cancer and has the lowest risk for compliceation>
TPC + ileostomy
NOt the first choice for patietn who have FAP b/c of disadvantages ass. witha perment ileostomy
What is he translational research for FAP
nonsurgical managemetn
goal is to use chemo-preventivee agens to delay or avoid surgery
What drugs are being studied
inhibitors of cellular proliferation such as acetyslaicicylic acid (ASA)
NSAIDS,
5-amionsalicylates,
COX-2 inhibitors being teh most promisng class of drugs
when is non-surgical therapy preferred?
intra-abdominal desmoid tumors
First line drugs : NSAIDS and anti-estrogen agents
If those agents fail, then alpha or cytotoxic chemotherapy agents are used, priamrly in rapid growing or life-threatening tumors
