Midterm Flashcards
Law of Segregation:
Dominant and recessive traits exist and are passed on from parent to offspring
Law of Independent Assortment:
Traits are passed independently of other traits from parents to offspring
Penetrance:
Disease is expressed in 100% of people with a particular genotype, complete or incomplete
Adenine pairs with?
Thymine
Guanine pairs with?
Cytosine
A/T has how many H bonds?
Two
G/C has how many H bonds?
Three
Chargaff’s Rule:
The total number of purines in a DNA molecule is equal to the total number of pyrimidines
Purines
A, G
Pyrimidines
T, C
Thymine is replaced with X on mRNA
Uracil
DNA is synthesized in what direction?
5’ to 3’
The 5’ end houses what molecule?
Phosphate group
The 3’ end houses what molecule?
Hydroxyl Group
During DNA translation the mRNA is transported from X to Y?
Nucleus to cytoplasm
Start codon
AUG
Stop codon
UAA, UAG, UGA
How many chromosomes do humans have?
46 chromosomes
Pseudogenes:
Non-functioning copies of genes
Describe the structure from DNA to chromosome:
DNA -> nucleosomes (with histones) -> chromatin -> chromatin loops -> condensed chromatin loops -> chromosomes
Locus
location of a particular gene on a chromosome
Allele
homologous copies of a gene
Germinal mutation
Occurs during formation of an egg or sperm
Somatic mutation
Mutation occurs after conception
Chromosomal aberration
alteration in the number or the physical structure of a chromsome
What’s the most common trisomy?
Down Syndrome
Risk for Down Syndrome increases with advanced maternal age, what age?
35
When does the non-disjunction occur?
Meiosis II
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
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
Klinefelter Syndrome genotype
XXY
Fertility in those with Klinefelter syndrome?
Usually sterile, impaired spermatogenesis
What is the most common genetic abnormality associated with primary hypogonadism?
Klinefelter Syndrome
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
Turner Syndrome genotype
XO
Clinical manifestations of Turner Syndrome
female apperance, short wide chests, prominent neck folds, usually sterile, low estrogen, small breasts, normal mental development
Consequences of Turner Syndrome
primary amenorrhea, osteoporosis, diabetes/hypertension/hyperlipidemia, aortic dissection
What should be asked when collecting family history?
age, sex, ethnicity, general health, major illness/disease process, cause of death
Name our autosomal dominant diseases:
HD, familial hypercholesterolemia, NF1, PKD
Name our autosomal recessive diseases:
PKU, sickle cell anemia, CF, thalassemia
Name our X-linked dominant disease:
Fragile X Syndrome
Name our X-linked recessive diseases:
Hemophilia, Duchenne’s Muscular Dystrophy, Red-Green color blindness
Inborn error of metabolism:
some genetic disorders lead to errors in the synthesis of proteins
Phenylketonuria is a defect in X? cause Y to accumulate.
phenylalanine hydroxylase causing phenylalanine to accumulate
What is defective in cystic fibrosis?
Cystic fibrosis transmembrane conductor regulator (CFTR) gene
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.
CF follows what inheritance pattern?
Autosomal recessive
Most common CF mutation is?
F508
In Caucasians without a family history of CF, the risk of being a carrier is?
1/25
What is the life expectancy of someone with CF?
37 yo
What is the most common inherited disorder among Caucasians in the US?
Cystic fibrosis
How are newborns tested for CF?
Presence of increased levels of immunoreactive trypsinogen (IRT), a pancreatic protein linked to CF
Fertility in CF?
98% of males are infertile due to absence of vas deferens
What type of heart failure may a CF patient experience?
cor pulmonale (right-sided heart failure)
Severe Combined Immunodeficiency (SCID): deficiency of
deficiency of B cells and T cells which allow humans to fight off serious infections
What’s the most common gene implicated in SCID?
defect in IL2RG (interleukin 2 receptor gamma)
How is SCID identified in newborn screenings?
biomarkeres for naive T cells
What % of the sperm deposited in the vagina enters the cervix?
1%
Where does fertilization occur?
widest part of the Fallopian tube, the ampullary region
What are the three phases of human development?
pre-embryonic, embryonic, fetal
Timeframe for pre-embryonic phase?
After fertilization and ends with implantation (week 1)
What occurs at day three of human development?
zygote starts to undergo cellular division and eventually forms a morula
What does the morula become after accumulates fluid?
Forms a blastocyst
What does the inner cell mass become?
Embryo
What does the trophoblast become?
Placenta
What happens at days 6 or 7 of human development?
Blastocyst will attach to uterine wall and begin to digest uterine wall for nourishment
What is the timeframe for the embryonic stage?
day 8 through week 8
What begins to differentiate within the ICM:
Ectoderm, mesoderm, endoderm
Ectoderm:
epidermis, hair, nails, sweat glands, brain and spinal cord, ocular structures, inner ear, nasal, oral, anal epithelium
Mesoderm:
dermis, muscles, cartilage, bone, blood, reproductive organs, teeth enamel
Endoderm:
digestive tract lining, respiratory tract lining, urethra and bladder, gallbladder, liver, and pancreas, thyroid, parathyroid, thymus, kidneys
What’s the time frame for the fetal stage?
week 8 to birth (40 weeks from LMP)
When is growth rate of length rapid?
3rd-5th month
When does rapid weight accelerations occur in pregnancy?
last 2 months
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
% of fertilization that end in spontaneous abortion
31%
% of infants born with structural abnormalities
3%
What is the critical period for teratogenesis?
3-16 weeks (organogenesis)
If teratogenesis occurs during preimplantation what is the result?
spontaneous abortion
If teratogenesis occurs during embryonic stage what is the result?
spontaneous abortion, structural malformation
If teratogenesis occurs during fetal stage what is the result?
CNS, growth restriction, neurobehavioral, reproductive effects, fetal demise
Some of the fetus’s blood vessels are contained in X that extend into the wall of the uterus
villi of the placenta
complete absence of limb or limbs
amelia
partial absence of limb
meromelia
absence of long bones with hands and feet attached to trunk with small rudimentary bones
phocomelia
Deformities associated with thalidomide
deafness, blindness, cleft palate, malformations of inner and outer ears
What was the legislation that was passed following thalidomide tragedy?
Kefauver-Harris Drug Amendments Act in 1962
Women who were prescribed DES while pregnant experience:
modest increase in the relative risk for breast cancer
DES daughters are at risk for:
clear-cell adenocarcinoma
Risk of clear-cell adenocarcinoma for DES daughtesr
1/1000
Incidence of clear-cell adenocarcinoma peaks at age?
20
DES daughters experience a twofold increase in?
vaginal and cervical intraepithelial neoplasm
Fertility of DES daughters?
infertility and poor pregnancy outcomes due to malformation of uterus, decreased endometrial thickness, reduced uterine perfusion
DES sons experience:
epidydimal cysts, microphallus, cryptorchidism, testicular hypoplasia, decreased sperm count
DES son fertility?
Fertile
Unit of supplemental vitamin A that increases risk of deformity
10,000 units
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
What is isotretinoin (Accutane)?
Vitamin A isomer of 13-cis-retinoic acid
What is the most potent teratogen currently in use?
isotretinoin (accutane)
What program is associated with accutane use?
iPLEDGE
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.
Use of angiotensin converting enzyme (ACE) inhibitors during 2nd and 3rd trimester cause?
growth retardation, renal dysfunction, fetal demise, and oligohydraminos
Selective Serotonin Reuptake Inhibitors (SSRIs) can result in:
increased cardiovascular defects, spontaneous abortion
Late exposure to SSRIs can cause
transient newborn respiratory distress
Anticonvulsant expsosure results in:
cleft palate, cleft lip, atrial septal defects, spina bifida, developmental delay, limb abnormalities
Use of NSAIDs during first trimester:
increased risk of having a baby with cardiac ventricular and septal defects
Use of NSAIDs during third trimester:
pulmonary hypertension
First trimester exposure to warfarin (coumadin)
nasal hypoplasia, long bone development abnormalities, limb hypoplasia
Benzodiazepine use:
neonatal withdrawal, hypotonia, cyanosis, floppy infant syndrome
The fetus eliminates alcohol at a rate of % of that of the mother
3-4%
Smallest effects recognized at X drinks/day and become more evident at x drinks/day
2, 4
Most FAS occurs in mothers who are alcoholics (x drinks/day)
8-10
Physical features of FAS
railroad track ears, ptosis, decreased elbow pronation/supination, incomplete extension of digits, defects in palmar crease = hockey stick crease
Prenatal nicotine exposure can reduce the cardiorespiratory response to low oxygen levels in sleep which can lead to
SIDS
Smoking can result in the following risks to the mother:
infertility, placenta previa, preterm premature rupture of membranes, placental abruption
Nicotine exposure can lead to:
cleft lip or plate, gastroschisis, atresia, LBW
What is the most commonly abused illicit drug of pregnancy?
Marijuana
Cocaine can lead to: (in the mother)
MI, arrhythmias, aortic rupture, CVA, seizure, bowel ischemia, sudden death
Cocaine can lead to: (fetus)
spontaneous abortion, fetal demise, premature birth, tremors, high-pitched cry, excess suck, hyper-alterness, apnea or tachypnea
Cocaine can stay in the infants system for?
7 days
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
TORCH stands for:
Toxoplasmosis, other, rubella, cytomegalovirus, herpes simplex
Toxoplasmosis is what type of infection?
protozoan parasite
How is toxoplasmosis spread?
fecal matter of cats, undercooked meat
Symptoms of toxoplasmosis in mother?
asymptomatic, fatigue, fever, headache, malaise, myalgia, lymphadenopathy
Symptoms of toxoplasmosis in baby?
chorioretinits, hydrocephalus, intracranial calcifications, learning disabilities, vision abnormalities
“Other” primarily refers to:
congenital syphilis
Syphilis is caused by:
treponema pallidum
Presentation of congenital syphillis:
nasal discharge, hepatomegaly, rashes on soles of feet and palms of hands, lymphadenopathy, CNS involvement
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
Is Rubella common in the US?
NO
Presentation of rubella
purpura and petechia, hearing impairment, congenital heart defects, cataracts
Symptoms of cytomegalovirus are similar to what illness?
Mono
Symptoms of CMV:
fever, rhinitis, pharyngitis, myalgias headache, fatigue
Morality rate of infants with congenital infection is?
5%
Cytomegalovirus presentation:
hearing loss, vision impairment due to chorioretinitis, microcephaly, seizures, jaudnice, petechia and purpura
Maternal herpes simplex symptoms:
genital ulcers with fever, lymphadenopathy, fever
Intrauterine disease dissemination of herpes simplex is rare but can result in:
infarcts of placenta, inflammation of umbilical cord, fetal demise, ocular damage
Herpex simplex results in this common category of symptoms:
Skin, Eye, Mouth Manifestations (SEM)
SEM manifestations in herpes simplex:
vesicles on erythematous base, ocular infections, cataracts, chorioretiniits, ulcerations of mouth, hepatitis unable to regulate temp, Disseminated Intravascular Coagulation
Amyloid plaques
abnormal deposits of a protein called beta amyloid that is found in the sapce between neurons
Neurofibrillary tangles
formed by clumps of tau protein
Important manifestations in Alzheimer’s Disease:
anomia (can’t name things), circumlocution, apraxia (inability to perform a learned task)
Early onset of Alzheimer’s is at what age?
30-60 yo
% of alzheimer’s cases are related to early onset genes?
1-5%
Early onset Alzheimer’s follows what inheritance pattern?
Autosomal dominant
What three genes are involved in Early Onset Alzheim’ers?
Amyloid precursor protein (APP gene), Presenilin 1 (PSN1), Presenilin 2 (PSN2)
Amyloid precursor protein (APP gene):
maybe involved in synaptic transmission
Presenilin 1 (PSN1):
overproduction of a longer and more toxic beta amyloid peptide and plaque formation
Presenilin 2 (PSN2)
rarest, increases apoptosis in neurogeneration
Late Onset Alzehimer’s begins after?
age 65
Genes involved in late onset AD
APOE epsilon 2, APOE epsilon 3, APOE epsilon 4
APOE Epsilon 2
least common, reduces risk
APOE Epsilon 3
Most common, neutral role
APOE Epsilon 4
increases risk for AD, earlier onset
Is testing recommended for late-onset AD?
No
Is testing recommended for early onset AD?
If desired
For HD, onset before age X is considered juvenile HD?
20 yo
HD follows which inheritance pattern?
Autosomal dominant
HD gene codes for a protein called?
Huntingtin
Mutated form of HD gene consists of an expanded X trinucldeotide repeat?
CAG
CAG codes for?
Glutamine
Inhertiance of HD allele from father results in?
3 year earlier onset of disease
Describe the CAG repeats in a negative, uninformative, or positive result for HD:
<35: negative
36-39: uninformative
>40: positive
Is Neurofibromatosis 1 or 2 more common?
NF1
Neurofibromatosis 1 inheritance pattern?
Autosomal dominant
Normal NF1 gene produces a protein called:
neurofibromin, NF1 is a tumor suppressor gene
Penetrance of NF1?
Complete penetrance but highly variable in presentation
Clinical manifestation of NF1?
cafe-au-lait macules (6+), freckling, Lisch nodules, neurofibromas, pseudoarthrosis of long bones, cognitive defects
Three types of neurofibromas:
cutaenous, plexiform, nodular
Neurofibromatosis 2 results in the development of:
noncancerous tumors on the auditory and vestibular nerves of the body
Tumors in NF2 are known as:
schwannomas
Does NF1 or NF2 have more cutaenous manifestations?
NF1
NF2 follows what inheritance patter?
Autosomal dominant
NF2 involves what protein?
Merlin aka schwannomin
Polycystic kidney disease follows which inheritance pattern?
Autosomal dominant (APPKD), rarely autosomal recessive (ARPKD)
PKD results in mutations of
PKD1 or PKD2
PKD1 encodes for
polycystin-1
PKD2 encodes for
polycystin-2
is PKD1 or PKD2 associated with more severe symptoms?
PKD1
What is the most dangerous complication of PKD?
intracranial aneurism
Hemochromatosis follows which inheritance pattern?
autosomal recessive disorder with variable penetrance
Hemochromatosis caused by a mutation in which gene?
HFE gene
Two most common point mutations in hemochromatosis exist at sites:
C282Y and H63D
Who is impacted more in HHC, men or women?
Men
Hemophilia is caused by mutation in which genes on the X chromosome?
F8 or F9 genes
Hemophilia A and B follow which pattern of inheritance?
X-linked recessive
Hemophilia A is a disorder of which gene?
F8
Is hemophilia A or B more common?
A
Hemophilia B is a disorder of?
F9
Hemophilia B is also called?
Christmas disease
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
How does genetic testing for hemophilia work?
Specific coagulation factor assays
Hemophilia C deficient in:
Factor XI
Hemophilia C follows which inheritance pattern:
Autosomal recessive pattern
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
What is the most commonly inherited bleeding disorder?
Von Willebrand Disease
What is the most common type of VW disease?
Type 1
Type 1 VW disease:
Low VWF levels, mild symptoms, probably AD
Type 2 VW diease:
Normal VWF levels but VWF doesn’t work correctly, moderate symptoms, AD or AR
Type 3 VW disease:
Little or no VWF, rare, severe symptoms, AR
Normal hemoglobin in adults is comprised of:
two alpha polypeptide chains and two beta polypeptide chains
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
Sickle cell anemia follows what inheritance pattern?
autosomal recessive
Sickle cell trait means?
heterozygote/carrier
Having the sickle cell triat provides protection against
cerebral malaria, often before age 16 months
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
A common presentation of sickle cell anemia patients in the ER is?
Acute chest syndrome (chest pain, dyspnea, fever)
Monogenic mutations leading to high cholesterol have been identified on the?
LDLR gene
Familial hypercholesterolemia follows?
AD or AR depending on mutation
LDLR gene encodes for:
low-density lipoprotein receptor
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
Homozygous form of FH results in LDL being ?x normal
8x
Heterozygous form of FH results in LDL being ?x normal
2-3x
firm-to-hard subcutaenous nodule with normal overlying skin, found in the tendons
tendon xanthomas
sharply demarcated yellowish collection of cholesterol underneath the skin, usually on or around the eyelids
Xanthelasma
FH has high risk of:
Coronary Heart Disease
Common manifestation of FH:
Tendon xanthomas, xanthelasma
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
What is one of the most common disorders of CT?
Marfan Syndrome
How is Marfan Syndrome inherited?
Autosomal dominant or de novo mutation in fibrillin-1 gene (FBN1)
Fibrillin-1 encodes for:
glycoprotein fibrillin which is a principal component of microfibril which is part of the structure of collagen
What is the most concerning issue with Marfan Syndrome?
Aortic dilation
What is the main cause of morbidity and mortality in Marfan Syndrome?
Aortic root disease
What is the name for arm span > body height?
dolichosternomelia
Funnel chest:
pectus carinatum
Pigeon chest:
pectus excavatum
too many toes sign
Hindfoot valgus
Flat foot
Pes planus
Dislocated lens
Ectopia lentis
What criteria is used to determine Marfans?
Ghent criteria + family history
A thoracic aortic aneurysm is defined as having:
> 50% increase in the expected diameter of that portion of the aorta
What disease is associated with aortic aneurysms?
atherosclerosis
During a dissection, where does a tear form?
Intima and then progresses to media
What is the mortality rate of an aortic dissection?
1-2% per hour
Two types of aortic dissection?
Type A, B
Type A aortic dissection begins?
ascending aorta
Type B aorta dissection begins?
descending aorta
The four P’s of aortic dissection:
pallor, pulselessness, paresthesia, paralysis
Familial Thoracic Aortic Aneurysms inheritance pattern:
autosomal dominant
Order the following based on age of presentation (oldest to youngest):
sporadic TAA, Familial TAA, Marfans
In familial TAA, which part of the aorta is involved 80% of the time?
Ascending
Four types of cardiomyopathies:
dilated, hypertrophic, restrictive, arrhythmogenic
Dilated cardiomyopathy
dilation of at least one ventricle which results in impaired contraction of one or both ventricles
Hypertrophic cardiomyopathy
myocardium becomes thickened, especially in left ventricle
Restrictive cardiomyopathy
stiffening and rigidity of the ventricles due to replacement of normal myocardium by scar tissue, no hypertrophy of ventricle
Arrhythomogenic cardiomyopathy
right ventricular myocardium replaced with scar tissue
What’s the leading cause of sudden cardiac death in athletes?
hereditary cardiomyopathies
Two most common hereditary cardiomyopathies:
Hypertrophic cardiomyopathy (HCM) and Arrhythmogenic cardiomyopathy/arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C)
Hypertrophic cardiomyopathy (HCM):
disorder of the left ventricle
Arrhythmogenic cardiomyopathy/arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C)
disorder of the right ventricle
What causes unexplained left ventricular hypertrophy (LVH)?
genetic mutations in one of several sarcomere genes
Mutations related to HCM:
mutations involve coding for thick or thin filaments of the sarcomere
HCM inheritance pattern:
AD
Manifestations of HCM:
left ventricular hypertrophy, impaired left ventricular contractility, dyspnea on exertion, palpitations, chest pain, syncope
ARVD/C manifestations
right ventricular abnormality, arrhythmias, palpitations, chest pain, syncope
ARVD/C is characterized by
fibrofatty replacement of right ventricle myocardium and myocardial thinning, RV dilation
ARVD/C inhertiance pattern
AD, very rarely AR
Pathogenesis of ARVD/C is related to:
desmosome dysfunction, myocyte detachment and cell death, inflammation, fibrofatty replacement of damaged mycoytes
Lifetime risk for breast cancer:
10-13%
What % of breast and ovarian cancer is attributed to genetics?
5-10%
BRCA1 and BRCA2 related cancers inheritance pattern:
AD with high penetrance
BRCA1 and BRCA2 are what type of genes?
Tumor suppressor genes
Which BRCA is associated with a higher lifetime risk of development of cancer?
BRCA1
Cumulative risk of breast cancer by age 70: BRCA1 and 2
BRCA1: 57%, BRCA2: 49%
o First childbirth at later ages associated with increased breast cancer risk in
BRCA2 carriers
Oral contraceptive use:
decreased rates of ovarian cancer in BRCA1/2 carriers, but possible could increase breast cancer rates
Risk of male breast cancer with BRCA2
6%
o Lifetime risk of ovarian cancer by age 70 for BRCA1/2
BRCA1: 40%
BRCA2: 18%
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
One of the first signs of colorectal cancer in your patient may be:
anemia
Two hereditary colorectal cancer syndromes:
Familial Adenomatous Polyposis (FAP), Heredtiary nonpolyposis colorectal cancer (HNPCC)
Risk of developing colon cancer for FAP
100%
Age of onset of colon cancer in FAP
39
Inhertience for FAP
Most common: AD caused by mutations in APC gene, less common: AR caused by mutations in MYH gene
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
MYH gene encodes for:
MYH glycolase, which specifically corrects error when guanine pairs with adenine instead of cytosine
Attenuated Familial Adenomatous Polyposis: key characteristic
fewer polyps, lower lifetime risk of cancer
Where are the adenomas located in AFAP?
right colon
Mutations are located where for FAP?
middle of APC gene
Mutations are located where for AFAP?
ends of APC gene
An extracolonic manifestation of FAP?
Gardner Syndrome
Gardner Syndrome
cancer in multiple places
Hereditary Nonpolyposis colorectal cancer aka
Lynch Syndrome
Characteristics of HNPCC:
fewer polyps, polyps are flatter, larger, and undergo rapid transformation to cancer
HNPCC colon cancer occurs where?
right side of colon
In HNPCC could progress from normal colonoscopy to cancer in?
2-3 years
Most common site of extracolonic cancer in HNPCC?
uterus (endometrium)
Lynch Syndrome inheritance?
Autosomal dominant, defect in a mismatch repair gene
Genes implicated in Lynch Syndrome?
MLH1, MSH2, MSH6, PMS2
Which specific defect results in higher endometrial risk and less CRC risk within lynch syndrome?
MSH6
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)
Inheritance pattern of Peutz-Jehgers Syndrome?
AD
Characteristic of Peutz-Jehgers Syndrome:
melanocytic macules on lips, perioral, and buccal regions. Increased GI polyps, risk of various cancers.
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
Symptoms of chronic myelogenous leukemia
elevated WBC count, fatigue, night sweats, fever, splenomegaly, weight loss, bleeding episodes
What chromosome impacted in chronic myelogenous leukemia?
Philadelphia chromosome (changed chromsome 22, part of 9)
The philadelphia chromosome results in:
increased tyrosine activity which are involved in signal transduction
Inheritance pattern of CML?
Not inherited!
Inheritance pattern of familial aytpical multiple mole syndrome (FAMM)?
Ad, impacts oncogenes and tumor suppressor genes
Genes involved in FAMM?
CDKN2A, MC1R
CDKN2A
encodes proteins P16 and P14ARF, responsible for decelerating cell’s progression from G1 phase to S phase
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
