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
