Genetic Diseases Flashcards
(90 cards)
1
Q
what is the most common chromosomal abnormality in live births
A
Down syndrome
95% caused by Trisomy 21, 4% caused by Robertsonian translocation
2
Q
What is Trisomy 21 linked to
A
advancing maternal age
Age 35= 1:400
Age 45= 1:35
3
Q
How can you test for Trisomy 21
A
Quad screen (maternal serum AFP, estriol, hCG, and inhibit-alpha)- levels can be too low or too high Nuchal translucency- added to results of quad screen for accuracy
4
Q
What is nuchal translucency
A
an ultrasound done on baby in mom’s tummy checking thickness of neck. the thicker the neck, the more likely the baby is of having trisomy 21
5
Q
How does Trisomy 21 develop
A
a gamete has two copies of chromosome 21, leading to a trisomy when fertilized
6
Q
When are parental chromosome studies indicated
A
when the trisomy was due to an unbalanced translocation
7
Q
What is the prevalence of Trisomy 21
A
1:500 pregnancies
8
Q
What are possible effects of Down Syndrome
A
intellectual disability, characteristic facial appearance, 40% have cardiac defects, 75% have hearing loss, 50% have visual problems, 7% have GI defects, increased social skills in childhood
9
Q
What do half of adults with Down Syndrome develop
A
Alzheimer disease
10
Q
What is the second most common form of autosomal trisomy that goes full term
A
Trisomy 18- Edwards syndrome
85% lost between 10 weeks gestation and term, 50% die in first week of life, 2% survive to 1 year
11
Q
What are characteristics of Edwards Syndrome
A
Rocker bottom feet
Kidney/Heart defects, developmental delay, club foot, low set ears/small jaw
12
Q
What is the incidence of Trisomy 18
A
1:5000 live born infants
Increased risk with maternal age
13
Q
What is Trisomy 13
A
Palau syndrome
14
Q
What is the incidence of Patau syndrome
A
1:16000 live births
seen with advancing maternal age
15
Q
What are effects of Trisomy 13
A
severe intellectual disability, cleft lip/palate, seizures, small jaw, polydactyly, heart defects, brain/spinal cord abnormalities
16
Q
What is the etiology of Patau syndrome
A
most cases due to true trisomy on chromosome 13.
Some caused by Robertsonian translocation involving chromosomes 13 and 14- part of 13 gets attached to 14, leading to 2 normal copies of 13 plus extra copy attached to another chromosome
17
Q
What is Cri-du-chat
A
a chromosomal abnormality that occurs due to deletion of short arm of chromosome 5 (partial monosomy) affecting 1:50,000 births
18
Q
How does Cri-du-chat occur
A
usually due to spontaneous mutation
19
Q
What are characteristics of cri-du-chat
A
cat like cry due to abnormal larynx development, intellectual disability, wide set eyes, low ears
20
Q
How can you test for cri-du-chat
A
in utero with CVS
21
Q
What is Klinefelter’s syndrome
A
when there is an extra X chromosome (47XXY) due to genetic mutation in gametogenesis. Many are lost during first trimester
22
Q
What are characteristics of Klinefelter’s syndrome
A
affects male physical and cognitive development.
physical traits apparent after puberty; hypogonadism, infertility, gynecomastia, reduced hair
23
Q
What is Turner syndrome
A
Genetic mutation leading to monosomy of x chromosome (45X) affecting development in females. Not commonly discovered until menstruation doesn’t occur
24
Q
What are characteristics of Turner syndrome
A
Gonadal dysgenesis, short stature, broad chest, webbed new, amenorrhea, infertility, cardiovascular abnormalities
25
What is Huntington's disease
An autosomal dominant, neurodegenerative disease/progressive brain disorder due to HD gene on chromosome 4 that codes for protein Huntingtin. It is the only human disorder for complete dominance
26
What are early signs of Huntington's disease
depression, irritability, poor coordination, trouble learning
27
At what age is Huntington's onset
usually adult onset, it is latent for 3-5 decades before manifesting as progressive neuronal dysfunction. However, if passed from previous generation, onset is likely to occur sooner
28
What are fun blown Huntington's characteristics
uncontrolled movements (chorea), emotional problems, loss of thinking ability, changes in personality
29
What is Huntingtin
a CAG nucleotide repeat 36-120 repeats (diseased state) that causes microscopic deposits of protein in neurons
30
What is the likelihood of survival in Huntington's
After symptoms present, usually 15 years. There is no treatment
31
How is Huntington's disease transferred
Most cases inherited, some can be spontaneous. If one parent has the disorder, each kid has 50% chance of manifesting. heterozygotes are just as affected as homozygotes (HH, Hh)
32
What is Alzheimer's
neurodegenerative disease causing the most common form of dementia in older individuals.
Early onset AD (familial) is more rare and late onset AD (sporadic) is more common
33
What population is at risk for Alzheimer's
usually above age 60. risk increases with age. People with parent, sibling, or child with AD are at increased risk
34
What is the survival rate of individuals with Alzheimer's
death within 10 years
35
What is the pathophysiology of Alzheimer's
loss of cholinergic neurons in brain (loss of acetylcholine), PLAQUE and TANGLE formation, brain atrophy, resulting in blocked communication
36
How is Alzheimer's transferred
several gene mutations can cause a predisposition to AD
37
What are characteristics of Alzheimer's
progressive mental deterioration, memory loss, confusion, disorientation
38
What is unique about Familial Alzheimer's
symptoms start before 65.
accounts for less than 5% of AD cases
Is autosomal dominant; 50% chance of developing if a parent has it
39
What is the etiology of Familial AD
mutation on chromosomes 1, 14, or 21 inducing a "sticky" protein that forms clumps in the brain
40
What is the etiology of Sporadic AD
Chromosome 19 apolipoprotein (APOE) gene shows increased risk. But not everyone carrying the gene develops the disease
41
What is unique about Sporadic AD
develops after age 65 and accounts for most cases of AD.
| Definitive diagnosis is autopsy plaques and tangles
42
What are clinical manifestations of hereditary breast and ovarian cancer syndrome
Early age breast cancer ( before 50), FH of both beast and ovarian cancer, increased bilateral cancers, increased development of both cancers, increased incidence of prostate cancer, male breast cancer
43
What are risk factors for HBOCS
gender, age, family history
44
How is HBOCS transferred
up to 10% caused by known predisposing genetic factors. If a pt has one mutated copy of either susceptibility gene (tumor suppressors BRCA-1, BRCA-2), their risk goes up. But, not all those with mutations on either BRCA gene develop cancer
45
How does a BRCA-1 gene mutation affect HBOCS
BRCA-1 is on chromosome 17.
mutation inherited in autosomal dominant manner.
not all families with this gene get hereditary breast cancer
46
How does BRCA-2 gene mutation affect HBOCS
BRCA2 is on chromosome 13.
mutation inherited in autosomal dominant manner.
Associated with male breast cancer, ovarian cancer, prostate cancer, and pancreatic cancer
47
How can you test for HBOCS
genetically test affected individual first.
| Identify whether BRCA1 or BRCA2 could be responsible for the cancer
48
What does colorectal cancer result from
interaction of genetic and environmental factors
genetic predisposition is main risk factor for a small portion of people.
Poor diet, smoking, lack of exercise are stronger risk factors
49
How is colorectal cancer transferred
mostly from sporadic mutations that occur randomly. Some can occur from familial inheritance
50
What are the two types of colorectal cancer
Familial adenomatous polyposis (FAP)- patterns within family without identifying a specific mutation. due to chance, shared exposure to carcinogen, or gene/environmental risk factors
Hereditary nonpolyposis colorectal cancer (HNPCC)-
51
What type of genetic mutation is familial adenomatous polyposis
```
autosomal dominant (50% chance of passing to kids) with mutation in APC gene (adenomatous polyposis coli), a tumor suppressor gene on chromosome 5
Less than 1% of colorectal cancers
```
52
How does FAP present
hundreds to thousands of polyps in colon, begin in adolescence.
Cancer develops in 20's.
risk of developing cancer is near 100% before 50.
Polyp to cancer, 10 years
53
What is the recommended diagnosis and treatment of FAP
offer genetic counseling and testing after colonoscopy.
Kids of FAP patient should have genetic testing by 10.
Total colectomy recommended before age 20
54
What is Hereditary nonpolyposis colorectal cancer
Lynch syndrome.
Autosomal dominant disease that accounts for 2-3% of colorectal cancers, occurring due to mutation of many genes that code for DNA repair
55
How is HNPCC different than FAP
more rapid transition from adenoma to cancer than FAP.
Cancers occur earlier, usually 30's and 40's.
small number to no polyps present in HNPCC
56
What is HNPCC associated with
50% chance of cancer in women, 70% chance in men.
| Associated with formation of other cancers- uterus, ovaries, stomach, urinary tract, small bowel, bile ducts
57
What should happen if genetic testing reveals HNPCC gene mutation
regular colonoscopy starting at 25, or 5 years younger than age of diagnosis of youngest affected family member.
Upper endoscopy every 2 years for gastric cancer screening.
Screen for endometrial and ovarian cancer at 25-35
58
What is the etiology of Chronic Myelogenous Leukemia
translocation between chromosomes 9 and 22 (philadelphia chromosome) causing a myeloproliferative disorder (blood cancer in red/white cells)
59
What is the function of Philadelphia chromosome
Chromosome 22- produces a protein that codes for enzyme that causes too many stem cells to develop into WBC
60
What is the pathophysiology of Chronic myelogenous leukemia
increased production of abnormal, nonfunctional WBC that end up taking up bone marrow space meant for healthy WBC, RBC and platelets
61
What is the clinical presentation of chronic myelogenous leukemia
insidious onset, slow progression over months-years of infections, anemia, bleeding
fever, night sweats, fatigue.
62
How do you diagnose chronic myelogenous leukemia
bone marrow aspiration for karyotype
63
What is hemophilia
a bleeding disorder caused by mutations in genes that code for coagulation proteins (F8 or F9 genes on X chromosome)
64
What do mutations of F8 and F9 cause
F8 causes factor VIII deficiency, resulting in hemophilia A (more common)
F9 causes factor IX deficiency, resulting in hemophilia B (christmas disease, less common)
65
What is the pattern of inheritance of Hemophilia
X-linked recessive pattern, so most affected individuals are men
66
What are clinical manifestations of Hemophilia
HEMARTHROSES (spontaneous bleeding into a joint), bleeding into muscles and other soft tissues, prolonged bleeding or oozing of blood after injury/surgery
67
What is the pathophysiology of Sickle Cell Disease
Atypical hemoglobin S molecules causing RBC to be crescent shaped and breakdown prematurely
Mutation is on HBB gene
68
What are clinical manifestations of sickle cell disease
anemia, infections, episodic pain due to destruction and infarct caused by sickle shaped cells getting stuck.
SOB, fatigue, delayed growth
69
What type of disease is sickle cell disease
autosomal recessive
most common in people with ancestors from Greece, Africa, Turkey, Italy, Arabian peninsula, India, South America, Central America, Caribbean
70
What is the pattern of inheritance of Cystic Fibrosis
autosomal recessive, two copies of mutated gene are needed for disease expression
71
What is the etiology of Cystic fibrosis
mutation on CFTR gene (cystic fibrosis transmembrane conductance regulator)- causes disruption of chloride and water transport, and disruption in water balance in secretions
72
What does CFTR code for
CFTR codes for protein that regulates chloride channels in epithelial cells
73
What are clinical manifestations of Cystic Fibrosis
thick, sticky mucous obstructing airways in lungs and pancreatic ducts.
Difficulty breathing, nutrient digestion difficulties (pancreatic enzymes can't reach intestine), failure to thrive, poor growth rate, MECONIUM ILEUS (thick fecal waste in infants due to intestinal obstruction).
Can also affect GU tract, hepatobiliary system, and exocrine glands
74
What can CF lead to
pulmonary disease because pulmonary system can't defend against pathogens well.
Sinusitis, bronchitis
Nasal polyps, nose bleeds, chronic sinus infections in kids
Thick mucous in lower airways cause obstruction
75
What are the most common organisms causing pulmonary disease in Cystic Fibrosis
S. Aureus, P. aeruginosa, Aspergireis (not the most common organisms for all respiratory diseases)
76
How can you diagnose Cystic Fibrosis
sweat chloride test (elevated chloride in CF). If positive, must confirm with genetic testing
77
What is Cystic Fibrosis
the most common genetic disease in white US population.
1:3500 white newborns born with disease
1:25 carrier incidence
most are diagnosed by age 1
78
What is the mode of inheritance of Marfan Syndrome
Autosomal dominant
| resulting from inherited or new mutation of FBN1 (fibrillar-1 gene)
79
What does Marfan Syndrome cause
defects in connective tissue affecting bones, ligaments, muscles, blood vessels, heart valves
80
What are clinical manifestations of Marfan Syndrome
tall stature, long thin arms and legs, arm span wider than body height, long narrow face, high arched palate, overcrowded teeth, scoliosis, hyper flexible joints, chest deformities
81
What are Key primary features of Marfan Syndrome
dislocated lens of eye causing vision problems
| aortic aneurysm/dissection
82
What are the major causes of morbidity and mortality
heart defects
| Mitral valve prolapse and aortic valve regurgitation that cause SOB, fatigue, palpitations
83
What should Marfan patients avoid
contact sports, caffeine, decongestants due to increased stress on CV system
84
What is the mode of inheritance of Neurofibromatosis Type I
von Recklinghausen disease (NF-1 most common)
Autosomal dominant
Due to mutation on NF1 gene on chromosome 17 (tumor suppressor gene), resulting in growth of neurofibromas (benign tumors on nerves of skin and brain) and change in skin pigmentation (darker)
85
What are diagnostic features of Neurofibromatosis I
```
CAFE-AU-LAIT
CROWE SIGN (axillary/inguinal freckling)
Lisch nodules in iris
2+ neurofibromas
optic glioma
1st degree relative with NF1
```
86
What is the pathophysiology of Polycystic Kidney Disease
clusters of fluid filled sacs develop in kidneys affecting ability to filter blood properly. Kidneys become enlarged and fail
87
What are clinical manifestations of PKD
```
HTN
back pain
hematuria
UTI/ renal stones
Also, liver cysts, heart valve abnormalities, increased risk for aortic or brain aneurysm
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88
What are the two forms of PKD
Autosomal dominant: Sx start as adult. inherited 90% of time. 1:1000 PKD1 and PKD2 genes
Autosomal recessive: rare, lethal in early life. 1:30,000. PKHD1 gene
89
What are congenital abnormalities caused by
variety of biological, chemical, and physical agents.
| Contributors are mutant genes, chromosomal defects, and multifactorial components
90
What is the biggest cause of birth defects
unknown etiology.
| Apps 10% of all newborns have some birth defect, from minor biochemical problem, to severe physical deformity
