Midterm Flashcards
1
Q
Law of Segregation:
A
Dominant and recessive traits exist and are passed on from parent to offspring
2
Q
Law of Independent Assortment:
A
Traits are passed independently of other traits from parents to offspring
3
Q
Penetrance:
A
Disease is expressed in 100% of people with a particular genotype, complete or incomplete
4
Q
Adenine pairs with?
A
Thymine
5
Q
Guanine pairs with?
A
Cytosine
6
Q
A/T has how many H bonds?
A
Two
7
Q
G/C has how many H bonds?
A
Three
8
Q
Chargaff’s Rule:
A
The total number of purines in a DNA molecule is equal to the total number of pyrimidines
9
Q
Purines
A
A, G
10
Q
Pyrimidines
A
T, C
11
Q
Thymine is replaced with X on mRNA
A
Uracil
12
Q
DNA is synthesized in what direction?
A
5’ to 3’
13
Q
The 5’ end houses what molecule?
A
Phosphate group
14
Q
The 3’ end houses what molecule?
A
Hydroxyl Group
15
Q
During DNA translation the mRNA is transported from X to Y?
A
Nucleus to cytoplasm
16
Q
Start codon
A
AUG
17
Q
Stop codon
A
UAA, UAG, UGA
18
Q
How many chromosomes do humans have?
A
46 chromosomes
19
Q
Pseudogenes:
A
Non-functioning copies of genes
20
Q
Describe the structure from DNA to chromosome:
A
DNA -> nucleosomes (with histones) -> chromatin -> chromatin loops -> condensed chromatin loops -> chromosomes
21
Q
Locus
A
location of a particular gene on a chromosome
22
Q
Allele
A
homologous copies of a gene
23
Q
Germinal mutation
A
Occurs during formation of an egg or sperm
24
Q
Somatic mutation
A
Mutation occurs after conception
25
Chromosomal aberration
alteration in the number or the physical structure of a chromsome
26
What's the most common trisomy?
Down Syndrome
27
Risk for Down Syndrome increases with advanced maternal age, what age?
35
28
When does the non-disjunction occur?
Meiosis II
29
Characteristics of a newborn with Down Syndrome:
hypotonia, flat facial features, enlarged and protruding tongue, small nose, upward slant of eyes, abnormally shaped ears, decreased palmar crease, hyperflexibility, extra space between first and second toe, brushfield spots
30
Clinical manifestations of Down Syndrome
cardiac defects, intestinal malformations, growth impairment, vision abnormalities, hearing loss, recurrent respiratory infections, behavioral issues, memory loss with an increased risk of Alzheimer's at an early age
31
Klinefelter Syndrome genotype
XXY
32
Fertility in those with Klinefelter syndrome?
Usually sterile, impaired spermatogenesis
33
What is the most common genetic abnormality associated with primary hypogonadism?
Klinefelter Syndrome
34
Those with Klinefelter Syndrome will have:
small testes with low sperm count, decreased serum testosterone, abnormal arm and leg length, increased risk of breast cancer and pulmonary disease, feminine appearing breasts
35
Turner Syndrome genotype
XO
36
Clinical manifestations of Turner Syndrome
female apperance, short wide chests, prominent neck folds, usually sterile, low estrogen, small breasts, normal mental development
37
Consequences of Turner Syndrome
primary amenorrhea, osteoporosis, diabetes/hypertension/hyperlipidemia, aortic dissection
38
What should be asked when collecting family history?
age, sex, ethnicity, general health, major illness/disease process, cause of death
39
Name our autosomal dominant diseases:
HD, familial hypercholesterolemia, NF1, PKD
40
Name our autosomal recessive diseases:
PKU, sickle cell anemia, CF, thalassemia
41
Name our X-linked dominant disease:
Fragile X Syndrome
42
Name our X-linked recessive diseases:
Hemophilia, Duchenne's Muscular Dystrophy, Red-Green color blindness
43
Inborn error of metabolism:
some genetic disorders lead to errors in the synthesis of proteins
44
Phenylketonuria is a defect in X? cause Y to accumulate.
phenylalanine hydroxylase causing phenylalanine to accumulate
45
What is defective in cystic fibrosis?
Cystic fibrosis transmembrane conductor regulator (CFTR) gene
46
What does the CFTR gene do?
helps regulate chloride channels in epithelial cells. Allows for chloride to be excreted and excess sodium uptake is inhibited, thus water content of secretions maintained.
47
CF follows what inheritance pattern?
Autosomal recessive
48
Most common CF mutation is?
F508
49
In Caucasians without a family history of CF, the risk of being a carrier is?
1/25
50
What is the life expectancy of someone with CF?
37 yo
51
What is the most common inherited disorder among Caucasians in the US?
Cystic fibrosis
52
How are newborns tested for CF?
Presence of increased levels of immunoreactive trypsinogen (IRT), a pancreatic protein linked to CF
53
Fertility in CF?
98% of males are infertile due to absence of vas deferens
54
What type of heart failure may a CF patient experience?
cor pulmonale (right-sided heart failure)
55
Severe Combined Immunodeficiency (SCID): deficiency of
deficiency of B cells and T cells which allow humans to fight off serious infections
56
What's the most common gene implicated in SCID?
defect in IL2RG (interleukin 2 receptor gamma)
57
How is SCID identified in newborn screenings?
biomarkeres for naive T cells
58
What % of the sperm deposited in the vagina enters the cervix?
1%
59
Where does fertilization occur?
widest part of the Fallopian tube, the ampullary region
60
What are the three phases of human development?
pre-embryonic, embryonic, fetal
61
Timeframe for pre-embryonic phase?
After fertilization and ends with implantation (week 1)
62
What occurs at day three of human development?
zygote starts to undergo cellular division and eventually forms a morula
63
What does the morula become after accumulates fluid?
Forms a blastocyst
64
What does the inner cell mass become?
Embryo
65
What does the trophoblast become?
Placenta
66
What happens at days 6 or 7 of human development?
Blastocyst will attach to uterine wall and begin to digest uterine wall for nourishment
67
What is the timeframe for the embryonic stage?
day 8 through week 8
68
What begins to differentiate within the ICM:
Ectoderm, mesoderm, endoderm
69
Ectoderm:
epidermis, hair, nails, sweat glands, brain and spinal cord, ocular structures, inner ear, nasal, oral, anal epithelium
70
Mesoderm:
dermis, muscles, cartilage, bone, blood, reproductive organs, teeth enamel
71
Endoderm:
digestive tract lining, respiratory tract lining, urethra and bladder, gallbladder, liver, and pancreas, thyroid, parathyroid, thymus, kidneys
72
What's the time frame for the fetal stage?
week 8 to birth (40 weeks from LMP)
73
When is growth rate of length rapid?
3rd-5th month
74
When does rapid weight accelerations occur in pregnancy?
last 2 months
75
Principles of teratogenesis:
susceptibility to teratogens is variable, susceptibility specific for stage development of embryo or fetus, mechanism of teratogen is specific for each teratogen, teratogenesis is dose dependent, teratogens produce death/growth retardation/malformation/functional impairment
76
% of fertilization that end in spontaneous abortion
31%
77
% of infants born with structural abnormalities
3%
78
What is the critical period for teratogenesis?
3-16 weeks (organogenesis)
79
If teratogenesis occurs during preimplantation what is the result?
spontaneous abortion
80
If teratogenesis occurs during embryonic stage what is the result?
spontaneous abortion, structural malformation
81
If teratogenesis occurs during fetal stage what is the result?
CNS, growth restriction, neurobehavioral, reproductive effects, fetal demise
82
Some of the fetus's blood vessels are contained in X that extend into the wall of the uterus
villi of the placenta
83
complete absence of limb or limbs
amelia
84
partial absence of limb
meromelia
85
absence of long bones with hands and feet attached to trunk with small rudimentary bones
phocomelia
86
Deformities associated with thalidomide
deafness, blindness, cleft palate, malformations of inner and outer ears
87
What was the legislation that was passed following thalidomide tragedy?
Kefauver-Harris Drug Amendments Act in 1962
88
Women who were prescribed DES while pregnant experience:
modest increase in the relative risk for breast cancer
89
DES daughters are at risk for:
clear-cell adenocarcinoma
90
Risk of clear-cell adenocarcinoma for DES daughtesr
1/1000
91
Incidence of clear-cell adenocarcinoma peaks at age?
20
92
DES daughters experience a twofold increase in?
vaginal and cervical intraepithelial neoplasm
93
Fertility of DES daughters?
infertility and poor pregnancy outcomes due to malformation of uterus, decreased endometrial thickness, reduced uterine perfusion
94
DES sons experience:
epidydimal cysts, microphallus, cryptorchidism, testicular hypoplasia, decreased sperm count
95
DES son fertility?
Fertile
96
Unit of supplemental vitamin A that increases risk of deformity
10,000 units
97
Babies born to mothers taking X units or more are 4x more likely to develop: cleft lip, cleft palate, hydrocephalus, cardiac deformities
20,000 units
98
What is isotretinoin (Accutane)?
Vitamin A isomer of 13-cis-retinoic acid
99
What is the most potent teratogen currently in use?
isotretinoin (accutane)
100
What program is associated with accutane use?
iPLEDGE
101
What does iPLEDGE entail?
two forms of birth control 1 month prior, during, and 1 month after. Two negative pregnancy tests prior to starting. Monthly pregnancy tests during and 1 month after.
102
Use of angiotensin converting enzyme (ACE) inhibitors during 2nd and 3rd trimester cause?
growth retardation, renal dysfunction, fetal demise, and oligohydraminos
103
Selective Serotonin Reuptake Inhibitors (SSRIs) can result in:
increased cardiovascular defects, spontaneous abortion
104
Late exposure to SSRIs can cause
transient newborn respiratory distress
105
Anticonvulsant expsosure results in:
cleft palate, cleft lip, atrial septal defects, spina bifida, developmental delay, limb abnormalities
106
Use of NSAIDs during first trimester:
increased risk of having a baby with cardiac ventricular and septal defects
107
Use of NSAIDs during third trimester:
pulmonary hypertension
108
First trimester exposure to warfarin (coumadin)
nasal hypoplasia, long bone development abnormalities, limb hypoplasia
109
Benzodiazepine use:
neonatal withdrawal, hypotonia, cyanosis, floppy infant syndrome
110
The fetus eliminates alcohol at a rate of % of that of the mother
3-4%
111
Smallest effects recognized at X drinks/day and become more evident at x drinks/day
2, 4
112
Most FAS occurs in mothers who are alcoholics (x drinks/day)
8-10
113
Physical features of FAS
railroad track ears, ptosis, decreased elbow pronation/supination, incomplete extension of digits, defects in palmar crease = hockey stick crease
114
Prenatal nicotine exposure can reduce the cardiorespiratory response to low oxygen levels in sleep which can lead to
SIDS
115
Smoking can result in the following risks to the mother:
infertility, placenta previa, preterm premature rupture of membranes, placental abruption
116
Nicotine exposure can lead to:
cleft lip or plate, gastroschisis, atresia, LBW
117
What is the most commonly abused illicit drug of pregnancy?
Marijuana
118
Cocaine can lead to: (in the mother)
MI, arrhythmias, aortic rupture, CVA, seizure, bowel ischemia, sudden death
119
Cocaine can lead to: (fetus)
spontaneous abortion, fetal demise, premature birth, tremors, high-pitched cry, excess suck, hyper-alterness, apnea or tachypnea
120
Cocaine can stay in the infants system for?
7 days
121
Chronic heroin use is associated with:
fetal growth restriction, abruptio placenta, fetal death, preterm labor, intrauterine passage of meconium, high-pitched cry, poor feeding, hypertonicity, GI distress, seizures, small for gestational age
122
TORCH stands for:
Toxoplasmosis, other, rubella, cytomegalovirus, herpes simplex
123
Toxoplasmosis is what type of infection?
protozoan parasite
124
How is toxoplasmosis spread?
fecal matter of cats, undercooked meat
125
Symptoms of toxoplasmosis in mother?
asymptomatic, fatigue, fever, headache, malaise, myalgia, lymphadenopathy
126
Symptoms of toxoplasmosis in baby?
chorioretinits, hydrocephalus, intracranial calcifications, learning disabilities, vision abnormalities
127
"Other" primarily refers to:
congenital syphilis
128
Syphilis is caused by:
treponema pallidum
129
Presentation of congenital syphillis:
nasal discharge, hepatomegaly, rashes on soles of feet and palms of hands, lymphadenopathy, CNS involvement
130
Presentation of congenital syphilis after 2 years of age:
frontal bossing, saddle nose, short maxilla, protuberant mandible, ocular and vision abnormalities, Hutchinson's teeth, fissures around mouth, neurological and skeletal abnormalities
131
Is Rubella common in the US?
NO
132
Presentation of rubella
purpura and petechia, hearing impairment, congenital heart defects, cataracts
133
Symptoms of cytomegalovirus are similar to what illness?
Mono
134
Symptoms of CMV:
fever, rhinitis, pharyngitis, myalgias headache, fatigue
135
Morality rate of infants with congenital infection is?
5%
136
Cytomegalovirus presentation:
hearing loss, vision impairment due to chorioretinitis, microcephaly, seizures, jaudnice, petechia and purpura
137
Maternal herpes simplex symptoms:
genital ulcers with fever, lymphadenopathy, fever
138
Intrauterine disease dissemination of herpes simplex is rare but can result in:
infarcts of placenta, inflammation of umbilical cord, fetal demise, ocular damage
139
Herpex simplex results in this common category of symptoms:
Skin, Eye, Mouth Manifestations (SEM)
140
SEM manifestations in herpes simplex:
vesicles on erythematous base, ocular infections, cataracts, chorioretiniits, ulcerations of mouth, hepatitis unable to regulate temp, Disseminated Intravascular Coagulation
141
Amyloid plaques
abnormal deposits of a protein called beta amyloid that is found in the sapce between neurons
142
Neurofibrillary tangles
formed by clumps of tau protein
143
Important manifestations in Alzheimer's Disease:
anomia (can't name things), circumlocution, apraxia (inability to perform a learned task)
144
Early onset of Alzheimer's is at what age?
30-60 yo
145
% of alzheimer's cases are related to early onset genes?
1-5%
146
Early onset Alzheimer's follows what inheritance pattern?
Autosomal dominant
147
What three genes are involved in Early Onset Alzheim'ers?
Amyloid precursor protein (APP gene), Presenilin 1 (PSN1), Presenilin 2 (PSN2)
148
Amyloid precursor protein (APP gene):
maybe involved in synaptic transmission
149
Presenilin 1 (PSN1):
overproduction of a longer and more toxic beta amyloid peptide and plaque formation
150
Presenilin 2 (PSN2)
rarest, increases apoptosis in neurogeneration
151
Late Onset Alzehimer's begins after?
age 65
152
Genes involved in late onset AD
APOE epsilon 2, APOE epsilon 3, APOE epsilon 4
153
APOE Epsilon 2
least common, reduces risk
154
APOE Epsilon 3
Most common, neutral role
155
APOE Epsilon 4
increases risk for AD, earlier onset
156
Is testing recommended for late-onset AD?
No
157
Is testing recommended for early onset AD?
If desired
158
For HD, onset before age X is considered juvenile HD?
20 yo
159
HD follows which inheritance pattern?
Autosomal dominant
160
HD gene codes for a protein called?
Huntingtin
161
Mutated form of HD gene consists of an expanded X trinucldeotide repeat?
CAG
162
CAG codes for?
Glutamine
163
Inhertiance of HD allele from father results in?
3 year earlier onset of disease
164
Describe the CAG repeats in a negative, uninformative, or positive result for HD:
<35: negative
36-39: uninformative
>40: positive
165
Is Neurofibromatosis 1 or 2 more common?
NF1
166
Neurofibromatosis 1 inheritance pattern?
Autosomal dominant
167
Normal NF1 gene produces a protein called:
neurofibromin, NF1 is a tumor suppressor gene
168
Penetrance of NF1?
Complete penetrance but highly variable in presentation
169
Clinical manifestation of NF1?
cafe-au-lait macules (6+), freckling, Lisch nodules, neurofibromas, pseudoarthrosis of long bones, cognitive defects
170
Three types of neurofibromas:
cutaenous, plexiform, nodular
171
Neurofibromatosis 2 results in the development of:
noncancerous tumors on the auditory and vestibular nerves of the body
172
Tumors in NF2 are known as:
schwannomas
173
Does NF1 or NF2 have more cutaenous manifestations?
NF1
174
NF2 follows what inheritance patter?
Autosomal dominant
175
NF2 involves what protein?
Merlin aka schwannomin
176
Polycystic kidney disease follows which inheritance pattern?
Autosomal dominant (APPKD), rarely autosomal recessive (ARPKD)
177
PKD results in mutations of
PKD1 or PKD2
178
PKD1 encodes for
polycystin-1
179
PKD2 encodes for
polycystin-2
180
is PKD1 or PKD2 associated with more severe symptoms?
PKD1
181
What is the most dangerous complication of PKD?
intracranial aneurism
182
Hemochromatosis follows which inheritance pattern?
autosomal recessive disorder with variable penetrance
183
Hemochromatosis caused by a mutation in which gene?
HFE gene
184
Two most common point mutations in hemochromatosis exist at sites:
C282Y and H63D
185
Who is impacted more in HHC, men or women?
Men
186
Hemophilia is caused by mutation in which genes on the X chromosome?
F8 or F9 genes
187
Hemophilia A and B follow which pattern of inheritance?
X-linked recessive
188
Hemophilia A is a disorder of which gene?
F8
189
Is hemophilia A or B more common?
A
190
Hemophilia B is a disorder of?
F9
191
Hemophilia B is also called?
Christmas disease
192
What are the three explanations for Female Symptomatic Hemophilia?
-X chromosome inactivation, mating between an affected male and carrier female, an abnormal karyotype resulting in loss of all or part of an X chromosome
193
How does genetic testing for hemophilia work?
Specific coagulation factor assays
194
Hemophilia C deficient in:
Factor XI
195
Hemophilia C follows which inheritance pattern:
Autosomal recessive pattern
196
Von Willebrand factor performs several functions:
- involved in platelet adhesion to the subendothelium
- receptors in platelets bind to VWF
- acts as a carrier for factor VIII in circulation
197
What is the most commonly inherited bleeding disorder?
Von Willebrand Disease
198
What is the most common type of VW disease?
Type 1
199
Type 1 VW disease:
Low VWF levels, mild symptoms, probably AD
200
Type 2 VW diease:
Normal VWF levels but VWF doesn't work correctly, moderate symptoms, AD or AR
201
Type 3 VW disease:
Little or no VWF, rare, severe symptoms, AR
202
Normal hemoglobin in adults is comprised of:
two alpha polypeptide chains and two beta polypeptide chains
203
Sickle cell anemia occurs due to
a single substitution at the 6th codon of the beta hemoglobin chain which casues the amino acid glutamic acid to be replaced with valine
204
Sickle cell anemia follows what inheritance pattern?
autosomal recessive
205
Sickle cell trait means?
heterozygote/carrier
206
Having the sickle cell triat provides protection against
cerebral malaria, often before age 16 months
207
Protective effect from malaria occurs because:
sickled hemoglobin is a strong inducer of heme-oxygenase 1 which produces carbon dioxide which produces host from cerebral malaria
208
A common presentation of sickle cell anemia patients in the ER is?
Acute chest syndrome (chest pain, dyspnea, fever)
209
Monogenic mutations leading to high cholesterol have been identified on the?
LDLR gene
210
Familial hypercholesterolemia follows?
AD or AR depending on mutation
211
LDLR gene encodes for:
low-density lipoprotein receptor
212
What does the low-density lipoprotein receptor do?
sits on outside of cell, where it binds to LDL from the circulation and transport it into the cell, where the cholsesterol is used by the cell, stored, or removed from the body
213
Homozygous form of FH results in LDL being ?x normal
8x
214
Heterozygous form of FH results in LDL being ?x normal
2-3x
215
firm-to-hard subcutaenous nodule with normal overlying skin, found in the tendons
tendon xanthomas
216
sharply demarcated yellowish collection of cholesterol underneath the skin, usually on or around the eyelids
Xanthelasma
217
FH has high risk of:
Coronary Heart Disease
218
Common manifestation of FH:
Tendon xanthomas, xanthelasma
219
Who should be screened for FH?
family member presents with FH, plasma cholesterol level in adult greater than 310 or child 230, premature cHD or sudden cardiac death, tendon xanthomas
220
What is one of the most common disorders of CT?
Marfan Syndrome
221
How is Marfan Syndrome inherited?
Autosomal dominant or de novo mutation in fibrillin-1 gene (FBN1)
222
Fibrillin-1 encodes for:
glycoprotein fibrillin which is a principal component of microfibril which is part of the structure of collagen
223
What is the most concerning issue with Marfan Syndrome?
Aortic dilation
224
What is the main cause of morbidity and mortality in Marfan Syndrome?
Aortic root disease
225
What is the name for arm span > body height?
dolichosternomelia
226
Funnel chest:
pectus carinatum
227
Pigeon chest:
pectus excavatum
228
too many toes sign
Hindfoot valgus
229
Flat foot
Pes planus
230
Dislocated lens
Ectopia lentis
231
What criteria is used to determine Marfans?
Ghent criteria + family history
232
A thoracic aortic aneurysm is defined as having:
>50% increase in the expected diameter of that portion of the aorta
233
What disease is associated with aortic aneurysms?
atherosclerosis
234
During a dissection, where does a tear form?
Intima and then progresses to media
235
What is the mortality rate of an aortic dissection?
1-2% per hour
236
Two types of aortic dissection?
Type A, B
237
Type A aortic dissection begins?
ascending aorta
238
Type B aorta dissection begins?
descending aorta
239
The four P's of aortic dissection:
pallor, pulselessness, paresthesia, paralysis
240
Familial Thoracic Aortic Aneurysms inheritance pattern:
autosomal dominant
241
Order the following based on age of presentation (oldest to youngest):
sporadic TAA, Familial TAA, Marfans
242
In familial TAA, which part of the aorta is involved 80% of the time?
Ascending
243
Four types of cardiomyopathies:
dilated, hypertrophic, restrictive, arrhythmogenic
244
Dilated cardiomyopathy
dilation of at least one ventricle which results in impaired contraction of one or both ventricles
245
Hypertrophic cardiomyopathy
myocardium becomes thickened, especially in left ventricle
246
Restrictive cardiomyopathy
stiffening and rigidity of the ventricles due to replacement of normal myocardium by scar tissue, no hypertrophy of ventricle
247
Arrhythomogenic cardiomyopathy
right ventricular myocardium replaced with scar tissue
248
What's the leading cause of sudden cardiac death in athletes?
hereditary cardiomyopathies
249
Two most common hereditary cardiomyopathies:
Hypertrophic cardiomyopathy (HCM) and Arrhythmogenic cardiomyopathy/arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C)
250
Hypertrophic cardiomyopathy (HCM):
disorder of the left ventricle
251
Arrhythmogenic cardiomyopathy/arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C)
disorder of the right ventricle
252
What causes unexplained left ventricular hypertrophy (LVH)?
genetic mutations in one of several sarcomere genes
253
Mutations related to HCM:
mutations involve coding for thick or thin filaments of the sarcomere
254
HCM inheritance pattern:
AD
255
Manifestations of HCM:
left ventricular hypertrophy, impaired left ventricular contractility, dyspnea on exertion, palpitations, chest pain, syncope
256
ARVD/C manifestations
right ventricular abnormality, arrhythmias, palpitations, chest pain, syncope
257
ARVD/C is characterized by
fibrofatty replacement of right ventricle myocardium and myocardial thinning, RV dilation
258
ARVD/C inhertiance pattern
AD, very rarely AR
259
Pathogenesis of ARVD/C is related to:
desmosome dysfunction, myocyte detachment and cell death, inflammation, fibrofatty replacement of damaged mycoytes
260
Lifetime risk for breast cancer:
10-13%
261
What % of breast and ovarian cancer is attributed to genetics?
5-10%
262
BRCA1 and BRCA2 related cancers inheritance pattern:
AD with high penetrance
263
BRCA1 and BRCA2 are what type of genes?
Tumor suppressor genes
264
Which BRCA is associated with a higher lifetime risk of development of cancer?
BRCA1
265
Cumulative risk of breast cancer by age 70: BRCA1 and 2
BRCA1: 57%, BRCA2: 49%
266
o First childbirth at later ages associated with increased breast cancer risk in
BRCA2 carriers
267
Oral contraceptive use:
decreased rates of ovarian cancer in BRCA1/2 carriers, but possible could increase breast cancer rates
268
Risk of male breast cancer with BRCA2
6%
269
o Lifetime risk of ovarian cancer by age 70 for BRCA1/2
BRCA1: 40%
BRCA2: 18%
270
Management of patients with hereditary breast and ovarian cancer syndrome:
o Clinical breast exam 2-4x annually starting at age 25
o Annual mammogram beginning ages 25-35 with consistent location and prior films
o Annual breast MRI
o Elective bilateral mastectomy: 90-95% risk reduction
o Annual or semiannual transvaginal US
o Annual CA-125 level (cancer antigen, non-specific, lots of benign conditions)
o Prophylactic bilateral salpingo-oophorectomy ages 35-40
271
One of the first signs of colorectal cancer in your patient may be:
anemia
272
Two hereditary colorectal cancer syndromes:
Familial Adenomatous Polyposis (FAP), Heredtiary nonpolyposis colorectal cancer (HNPCC)
273
Risk of developing colon cancer for FAP
100%
274
Age of onset of colon cancer in FAP
39
275
Inhertience for FAP
Most common: AD caused by mutations in APC gene, less common: AR caused by mutations in MYH gene
276
APC protein is associated with:
regulate cell division, cell adhesion, apoptosis, acts as a tumor suppressor, and ensures correct number of chromosomes are present in a cell before it divides
277
MYH gene encodes for:
MYH glycolase, which specifically corrects error when guanine pairs with adenine instead of cytosine
278
Attenuated Familial Adenomatous Polyposis: key characteristic
fewer polyps, lower lifetime risk of cancer
279
Where are the adenomas located in AFAP?
right colon
280
Mutations are located where for FAP?
middle of APC gene
281
Mutations are located where for AFAP?
ends of APC gene
282
An extracolonic manifestation of FAP?
Gardner Syndrome
283
Gardner Syndrome
cancer in multiple places
284
Hereditary Nonpolyposis colorectal cancer aka
Lynch Syndrome
285
Characteristics of HNPCC:
fewer polyps, polyps are flatter, larger, and undergo rapid transformation to cancer
286
HNPCC colon cancer occurs where?
right side of colon
287
In HNPCC could progress from normal colonoscopy to cancer in?
2-3 years
288
Most common site of extracolonic cancer in HNPCC?
uterus (endometrium)
289
Lynch Syndrome inheritance?
Autosomal dominant, defect in a mismatch repair gene
290
Genes implicated in Lynch Syndrome?
MLH1, MSH2, MSH6, PMS2
291
Which specific defect results in higher endometrial risk and less CRC risk within lynch syndrome?
MSH6
292
Lynch Syndrome protocols:
tumor testing, affected relatives should have colonoscopy every 1-2 years beginning at age 25 or at age 5 years prior to diagnosis of youngest family member, upper endoscopy performed every 2-3 years, screening for endometrial cancer and ovarian cancer with pelvic exam, CA125, transvaginal ultrasound (TVUS), endometrial biopsy at age 25-35, prophylactic TAH (total abdominal hysterectomy)
293
Inheritance pattern of Peutz-Jehgers Syndrome?
AD
294
Characteristic of Peutz-Jehgers Syndrome:
melanocytic macules on lips, perioral, and buccal regions. Increased GI polyps, risk of various cancers.
295
Chronic myelogenous leukemia is characterized by:
abnormally increased number of granulocytes -> uncontrolled proliferation that starves out space needed in bone marrow for other cell lines
296
Symptoms of chronic myelogenous leukemia
elevated WBC count, fatigue, night sweats, fever, splenomegaly, weight loss, bleeding episodes
297
What chromosome impacted in chronic myelogenous leukemia?
Philadelphia chromosome (changed chromsome 22, part of 9)
298
The philadelphia chromosome results in:
increased tyrosine activity which are involved in signal transduction
299
Inheritance pattern of CML?
Not inherited!
300
Inheritance pattern of familial aytpical multiple mole syndrome (FAMM)?
Ad, impacts oncogenes and tumor suppressor genes
301
Genes involved in FAMM?
CDKN2A, MC1R
302
CDKN2A
encodes proteins P16 and P14ARF, responsible for decelerating cell's progression from G1 phase to S phase
303
MC1R
regulate skin and hair color by controlling production of melanin/pigmentation, pheomelanin produces light skin, hair, and freckled individuals. mutations may increase penetrace of CDKN2A
