1
Q
Define Genes
A
Hereditary units of DNA transmitted from one generation to another; code for proteins
2
Q
Define Locus
A
The specific location of a gene on a chromosome
3
Q
Define Alleles
A
Different versions of a gene; humans have 2 alleles for each autosomal gene
4
Q
Define Chromosomes
A
- Structure composed of genes located in nucleus of a cell
- Chromosomes can be distinguished from each other by overall length and position of centromere (divides chromosome into 2 arms of varying length)
5
Q
Define Homologous chromosomes
A
Have the same genes at the same loci, one maternal and one paternal
6
Q
Define Genome
A
The genetic information contained in the cells, on the chromosomes, for a particular species
7
Q
Define a Mutation
A
-A change in some part of the DNA code
- Can be spontaneous or induced by exposure to mutagenic chemicals or radiation
- Varying effects depending on where in the gene code the mutation occurred
- Net result of a mutation may be a change in physical appearance or other some other trait
8
Q
Define Autosome
A
- Any chromosome that is not a sex chromosome (humans have 22 pairs of autosomes)
- Humans have one allosome pair (sex chromosome pair)
9
Q
What are the number of Chromosomes a person has
A
-Somatic cells contain one set of chromosomes from female parent and one homologous set from male parent
- Homologous chromosomes are similar in size, structure, and gene composition
- Humans have 22 pairs of autosomes, and 1 pair of sex chromosomes (allosomes) for 23 total pairs in each cell
10
Q
compare Haploid VS Diploid numbers of chromosomes
A
- Haploid number (n): the number of chromosomes in sex cells/gametes (n=23)
- Diploid number (2n): the total number of chromosomes in somatic cells (2n=46)
11
Q
Describe human chromosomes (physically)
A
- Short arm is the p arm
- Long arm is the q arm
- Each chromosome (except sex chromosomes) is numbered consecutively according to length beginning with longest chromosome first
12
Q
compare Autosomes VS Allosomes
A
- Autosomes: All chromosomes except sex chromosomes
- Allosomes: Sex chromosomes
13
Q
Describe sex chromosomes in males and females
A
- Human males have Heteromorphic chromosomes (X and Y)
- Genetic factors on the Y determine maleness
- Human females have two morphologically similar X’s
14
Q
Describe Mitosis
A
- The process by which all somatic cells become descendants of one original cell
- One exact copy of each chromosome is made and distributed through the division of original cell into two daughter cells
15
Q
Describe Meiosis
A
- The process by which gamete cells are produced (egg and sperm)
- Resulting gametes have 23 new chromosomes (one member of each of the pairs), with new combos of the original maternal and paternal copies
- Occurs only in specialized germ cells of gonads
- 2 consecutive cell divisions producing cells with half the original chromosome number. diploid 2n –> haploid n
16
Q
Describe differences in Gametogenesis in Males VS Females
DRAW THIS OUT
A
-MALE: Diploid primordial cells in testes become spermatogonia –> 4 sperm cells (spermatozoa), each is haploid (n)
-FEMALE: Diploid primordial cells in ovaries become
oogonia –> Diploid primordial cells in ovaries become
oogonia
17
Q
Describe Genotype
A
-All of the alleles of an organism
- Homozygous – contains the same alleles at a single locus
- Heterozygous – contains 2 different alleles at a single locus
18
Q
Describe Phenotype
A
- A measurable trait an organism has
- Result of gene products that interact in a given environment
19
Q
Describe Dominant allele
A
Phenotype can be seen in both the heterozygote and homozygote
20
Q
Describe a Carrier
A
Heterozygous individual with a recessive allele that’s hidden from phenotypic view by the dominant, normal allele
21
Q
Describe Recessive allele
A
Produces this phenotype only when its paired allele is identical
22
Q
What does the Punnett square illustrate?
A
A monofactorial cross – a mating in which a single gene is analyzed
23
Q
Albinism Punnett square example… DRAW IT OUT!
A=dominant, pigment-producing allele
a=recessive, albino (no pigment) allele
What is the result?
A
Produces 3 genotypes, 2 phenotypes
24
Q
Describe Codominance
A
- When two alleles for a trait are equally expressed (example: AB blood type)
- When alleles lack complete dominant and recessive relationships and are both observed phenotypically (expressed at the same time)
25
Describe Incomplete dominance
- Heterozygotes have phenotypes that have both alleles visible as a blend (one allele isn’t expressed over the other)
- Makes a third phenotype that’s a blending of the two
- Human examples: wavy hair – it’s a blend that’s seen when a person with straight hair has a child with a person with curly hair; skin color
26
Describe Penetrance
The probability that individuals in a population who have a particular gene combination will show the condition
27
Describe a Genetic marker
Sequence of DNA with a known location on a chromosome
28
Describe Expression
- The components of the phenotype that are exhibited in an individual
- Example: myotonic muscular dystrophy
- Phenotype may include myotonia, cataracts, narcolepsy, balding, infertility
- 2 people carrying this gene may express it differently: one may have cataracts and one has narcolepsy and grip myotonia
29
Describe Anticipation
- Genetic diseases that increase in severity or have earlier onset with each successive generation
- Examples: Fragile X, Huntington, myotonic muscular dystrophy
30
Describe Chromosomal Abnormalities
- Can be numerical or structural
| - Most common type is aneuploidy – abnormal number
31
What is balanced chromosomal abnormalities and two examples of it?
-No net loss or gain of chromosomal material
1) Balanced translocation – rupture of a chromosome resulting in the pieces “re-sticking” in the wrong combinations
2) Inversion – a chromosome piece is lifted out, turned around, and reinserted
32
Describe Unbalanced chromosomal abnormalities
-Additional or missing information (Deletion or Insertion)
33
Describe Unbalanced translocation
- Tends to arise as an offspring of a balanced carrier
| - Example: Robertsonian translocation
34
Describe Robertsonian translocation
- Involve any 2 out of chromosomes 13, 14, 15, 21, and 22
- They are all acrocentric (centromeres are close to the end)
- Results in formation of a “new” chromosome
- The bigger chromosome can produce an unbalanced gamete
- Those involving chromosome 21 can produce gametes with 2 copies; upon fertilization, can produce Trisomy 21
35
What are the Standard Symbols in Pedigree Language?
- Male -square
- Female – circle
- Diagonal line through symbol – deceased
- Shaded symbol – affected with trait
- Half-shaded symbol – carrier of trait
36
What are the Standard Lines in Pedigree Language?
- Relationship – line between individuals
- Sibship – horizontal line showing siblings
- Line of descent – line showing offspring
- Individual line – attaches to sibship line
- Two hash marks – divorced or separated (or no longer in a relationship)
37
Contrast Consultand VS Proband
- Consultand: The person seeking genetic advice. Represented by an arrow on pedigree. Can be healthy or a person with a condition
- Proband: The affected individual
38
What are some Pedigree Tips?
- Draw siblings in birth order from left to right; include either their age or their year of birth (1, 2, 3)
- Each generation goes on the same horizontal plane (I, II, III)
39
Describe Patterns of Inheritance and the Pedigree: Autosomal dominant
- 65% of human monogenic disorders
- Mutation in a single allele can cause disease
- Examples: Huntington’s Disease
- Affected individuals are HH or Hh (homozygous dominant or heterozygous)
- Those with genotypes hh are normal
40
Describe Characteristics of Autosomal dominant diseases
- Vertical pattern: Transmission passes from parent to offspring
- Multiple generations affected
- Variable expressivity: Affected individuals in same family may show varying degrees of phenotypic expression (severity)
- Reduced penetrance: Some with the genetic mutation may not show phenotype, making it appear that it “skipped” a generation
- Males and females affected equally
- Male to male transmission can be seen
41
Describe Patterns of Inheritance and the Pedigree: Autosomal Recessive
- 25% of human monogenic disorders
- 2 copies of diseased allele required for expressing the phenotype
- Tends to involve enzymes or receptors
- Rare
- Males and females equally affected
- Horizontal inheritance: Multiple affected offspring
- Often occurs in the context of consanguinity (In-family breeding)
- Heterozygous carriers of a defective allele are usually clinically normal
- Example: Cystic fibrosis
42
Describe Characteristics of Autosomal Recessive diseases
- Horizontal pattern
- Single generation affected
- Males and females affected equally
- Inheritance is from both parents, each being a heterozygote/carrier
- Each offspring has a 25% chance of being affected, and a 50% chance of being a carrier
- Higher association with consanguity
43
Describe Patterns of Inheritance and the Pedigree: X-Linked
- 5% of human monogenic disorders
- Risk of developing disease due to a mutant x chromosome differs between the sexes
- Males are hemizygous (heterozygous) for mutant allele on the X: More likely to develop a mutant phenotype regardless if the mutation is dominant or recessive
- The terms “x-linked dominant” and “x-linked recessive” therefore only apply to females
- Heterozygous females usually normal or mild
44
Describe Characteristics of X-Linked diseases
- No male to male transmission is possible
- Unaffected males do not transmit the phenotype
- All daughters of an affected male are heterozygous carriers
- Males usually more severely affected than females
Examples:
1) X-linked dominant: Alport’s Syndrome, Fragile X Syndrome
2) X-linked recessive: Wiskott-Aldrich Syndrome, Duchenne muscular dystrophy
45
Describe Patterns of Inheritance and the Pedigree: Multifactorial/Complex Disease
-Caused by interactions of variations in multiple genes and environmental factors
46
Describe Genetic susceptibility genes
-These genes make a person susceptible to a disorder, and certain environmental factors trigger the susceptibility.
-These are increasingly being identified for complex conditions such as:
Cancer
Diabetes
Asthma
Heart disease
Mental illness
Cleft lip/cleft palate
47
Describe Sporadic cancer vs. inherited cancer
- Sporadic cancer is more likely
| - Most cancer is NOT inherited, but the predisposition to cancer IS inherited
48
Describe Down Syndrome
-Gamete has two copies of chromosome 21: Trisomy 21
-Trisomy 21 is cause of 95% of cases of Down Syndrome
4% due to Roberstonian translocation
-Most common, non-lethal trisomy, chromosomal abnormality in live births
-Prevalence: 1:500 pregnancies
-Increase incidence with advancing maternal age
Age 35- 1:400
Age 45- 1:35
49
Describe Prenatal testing for Down Syndrome
- Quad screen: maternal serum AFP, estriol, hCG, inhibin-alpha
- Nuchal translucency: Ultrasound of fetus' neck
-Combination of these tests determines the thickness of the skin of the fetus, which helps determine if he/she has Down Syndrome
50
Describe Down Syndrome characteristics
- Intellectual disability
- Characteristic facial appearance
- 40% have cardiac defects
- 75% hearing loss
- >50% visual problems
- 7% have GI defects
- Increased social skills in childhood
- Half of adults with Down syndrome develop Alzheimer disease
51
Describe Trisomy 18
- AKA Edwards Syndrome
- Second most common autosomal trisomy after trisomy 21 that goes to full term
- Usually from 3 copies of 18, but translocation can occur
- Many die before birth or in first month
52
Describe Characteristics of Trisomy 18
- Kidney and heart defects
- Developmental delay
- Club foot (Rocker bottom feet)
- Low set ears, small jaw
53
Describe Trisomy 18 birth statistics
- 1:5000 live born infants
- Increased risk with advanced maternal age
- IUGR: Intrautero Growth Restriction
- Highly lethal in-utero – 85% lost between 10 weeks’ gestation and term
- 50% die in first week of life
- 2% 1 year survival rate
54
Describe Trisomy 13 birth statistics
- AKA Patau syndrome
- Increased risk with advanced maternal age
- 1:16000 live births
- Severe intellectual disability
- Many children die within first days or weeks of life
55
Describe Trisomy 13 characteristics
- Cleft lip or palate
- Seizures
- Small jaw
- Polydactyly
- Heart defects, brain/spinal cord abnormalities
56
Describe Trisomy 13 Etiology
- Most cases of Trisomy 13 ????????????
- Some caused by Robertsonian translocation involving chromosomes 13 and 14: A part of chromosome 13 gets attached to chromosome 14 during formation of gametes. Affected people have 2 normal copies of 13 plus an extra copy attached to another chromosome
57
Describe Cri-du-Chat Syndrome
- Deletion of part of short arm of chromosome 5
- Partial monosomy: when only a portion of a chromosome has one copy instead of two
- Most cases are from a spontaneous mutation
- Cat-like cry of affected children due to abnormal larynx development
- Intellectual disability, wide set eyes, low ears
- 1:50,000 births
- Can be detected in utero with CVS (Chorionic Villus Sampling)
58
Describe Klinefelter’s Syndrome *
- Extra X chromosome, 47 XXY
- Occurs during gametogenesis
- Affects male physical and cognitive development
- Accounts for many first trimester losses
- Physical traits become more apparent after puberty
- Most common sex chromosome aneuploidy in males
- Hypogonadism, infertility
- Gynecomastia, reduced hair
59
Describe Turner Syndrome *
- 45 X, affects development in females
- Monosomy
- ****Gonadal dysgenesis***** --> Non-functional ovaries
- Short stature
- Broad chest
- Webbed neck
- Amenorrhea
- Infertility
- Cardiovascular abnormalities
60
Describe Huntington’s Disease signs and symptoms *
- A neurodegenerative disease – progressive brain disorder
- Causes uncontrolled movements, emotional problems, and loss of thinking ability, changes in personality
- Early signs: depression, irritability, poor coordination, trouble learning
- Involuntary jerking movements: chorea
- Adult onset: genetic defect is latent for 3-5 decades, then manifests as progressive neuronal dysfunction
61
Describe Huntington’s Disease genetics *
- Genetic defect: HD gene on chromosome 4 that codes for a unique protein called huntingtin
- CAG trinucleotide repeat
- Normal: 10-35 repeats
- In HD: 36-120 repeats
- Abnormal protein (Glutamate) causes microscopic deposits of protein in neurons
- Most cases are inherited, but some occur as new spontaneous mutations
- Autosomal dominant: Only human disorder of complete dominance --> Anticipation
- Average time from symptom onset to death is 15 years
62
Describe Alzheimer’s Disease
- A neurodegenerative disease
- Progressive mental deterioration: memory loss, confusion, disorientation
- Most common form of dementia in older individuals
- Dementia
- 65% from Alzheimer’s Disease
- 35% vascular in nature
63
Describe Population of Alzheimer’s Disease
- Usually begins after age 60; risk increases with age
- Death usually occurs within 10 years
- People with parent, sibling, or child with AD are at increased risk
64
Describe Pathophysiology of Alzheimer’s Disease
- Loss of cholinergic neurons in brain (loss of acetylcholine)
- Formation of plaques and tangles
- Atrophy of brain
- Resultant effect – blocked communication
65
What are the two forms of Alzheimer’s Disease?
1) Familial... AKA early onset AD
| 2) Sporadic... AKA late onset AD
66
Describe Describe Familial AD
- Many members of multiple generations affected
- Symptoms start before age 65
- Mutations on chromosomes 1, 14, or 21: Induce formation of a “sticky” protein that forms clumps in the brain
- Rare - <5% of cases of AD
- Autosomal dominant: 50% chance of developing early onset AD if one parent has it
67
Describe Describe Sporadic AD
- Usually develops after age 65
- Accounts for most cases of AD
- One gene has been shown to increase risk
- Chromosome 19 apolipoprotein E (APOE) gene
- Not everyone carrying the gene develops disease
-Definitive diagnosis: *****autopsy-plaques and tangles of nervous tissue******
68
Describe Risk factors for Hereditary Breast and Ovarian Cancer Syndrome
Gender
Age
Family history
69
Describe the Mode of inheritance for Hereditary Breast and Ovarian Cancer Syndrome
Up to 10% of breast and ovarian cancers are caused by known predisposing genetic factors
70
Describe Clinical manifestations of Hereditary Breast and Ovarian Cancer Syndrome
- Early age of breast cancer onset (< 50)
- FH of both breast and ovarian cancer
- Increased bilateral cancers
- Increased development of both cancers in same person
- Increased incidence of prostate cancer in family
- Male breast cancer
71
What are the TWO major cancer susceptibility genes
- BRCA1 and BRCA2: Are tumor suppressor genes
- Normally control cell growth and death, and DNA repair and stability
- If a person has one mutated copy of either gene, their cancer risk goes up
72
Describe BRCA1
- First gene associated with breast cancer
- BRCA1 on chromosome 17
- Mutation is inherited in autosomal dominant manner
- Not all families with this gene get hereditary breast cancer
73
Describe BRCA2
- Second gene associated with breast cancer
- BRCA2 on chromosome 13
- Mutations is inherited in autosomal dominant manner
- Associated with male breast cancer, ovarian cancer, prostate cancer, and pancreatic cancer
74
Describe Genetic testing for Hereditary Breast and Ovarian Cancer Syndrome
- Preferable to first test an individual who is affected by cancer before testing unaffected family members
- Helps to identify whether a detectable BRCA1 or BRCA2 mutation could be responsible for the cancer
- An individual can inherit a BRCA1 or BRCA2 mutation yet never develop cancer
75
Describe Colorectal Cancer
- Results from the interaction of both genetic and environmental factors
- Genetic predisposition is the main risk factor in only a small proportion of people
- Diet, exercise, smoking, obesity are stronger risk factors in most people
- May occur sporadically or from familial inheritance
- Most are from sporadic mutations and occur randomly
- Many cancer syndromes include colon cancer
76
Describe Types of hereditary colon cancer
1) Familial colorectal cancer
2) Hereditary colorectal cancer syndromes
- Arise from specific mutations in genes that code for susceptibility to cancer
- Familial adenomatous polyposis (FAP) <1%
- Hereditary nonpolyposis colorectal cancer (HNPCC, Lynch Syndrome) 2-3%
77
Describe Colorectal Cancer family history
-Patterns within a family that exist without identifying a specific mutation are labeled as familial colorectal cancers
-A family history of one or more people with colorectal cancer or premalignant polyps is considered a positive FH
-May be due to:
Chance alone
Shared exposure to a carcinogen or diet/lifestyle factors
Combination of gene mutations and environmental risk factors
78
Describe Familial adenomatous polyposis (FAP)
- <1% of all colorectal cancers
- Pattern of inheritance: autosomal dominant
- Children of patient with FAP should have genetic screening by age 10 years
- Once diagnosis of FAP is established, total colectomy is recommended before age 20 years
79
Describe Genetic mutation that affects Familial adenomatous polyposis (FAP)
- Mutation in APC (adenomatous polyposis coli) gene
- Hundreds to thousands of polyps in colon beginning in adolescence
- APC is a tumor suppressor gene on chromosome 5
- Cancers develop in 20’s
- Risk of developing colorectal cancer is near 100%, usually before age 50
- Time from polyp to cancer development is 10+ years
80
Describe Hereditary Nonpolyposis Colorectal Cancer (HNPCC)
- AKA Lynch Syndrome
- 2-3% of all colorectal cancers
- Pattern of inheritance: autosomal dominant
- Genetic mutation: a mutation in one of many genes that code for DNA repair
- More rapid transition from adenoma to cancer than FAP – cancers occur earlier, 30’s and 40’s
81
What does Nonpolyposis refers to?
-The fact that colorectal cancer can occur when a small number or no polyps are present
82
Describe Hereditary Nonpolyposis Colorectal Cancer (HNPCC) cancer rates
- Approx. 50% chance of cancer in women, approx. 70% in men
- Associated with the formation of other cancers
- Uterus, ovaries, stomach, urinary tract, small bowel, bile ducts
83
Describe Hereditary Nonpolyposis Colorectal Cancer (HNPCC) maintenance
-Regular colonoscopy starting age 25 for relatives
Or beginning 5 years younger than the age of diagnosis of the youngest affected family member
-Upper endoscopy every 2 years to screen for gastric cancer
-Screening for endometrial and ovarian cancer in women at age 25-35
84
Describe Chronic Myelogenous Leukemia *
- A myeloproliferative disorder
- More common in men
- Median age at presentation is 55 years
85
Describe Genetic defects of Chronic Myelogenous Leukemia *
1) Translocation between chromosomes 9 and 22
2) ****Philadelphia chromosome (22) --> Produces a protein that codes for an enzyme that causes too many stem cells to develop into WBCs***
86
Describe the Pathophysiology of Chronic Myelogenous Leukemia
- Increased production of abnormal white blood cells that are nonfunctional
- These large numbers of abnormal WBCs take up bone marrow space meant for healthy WBCs, RBCs, and platelets
87
Describe the Clinical presentation of Chronic Myelogenous Leukemia
- Insidious onset, slow progression over months to years of infections, anemia, bleeding
- Fever, night sweats fatigue
- Diagnosis involves bone marrow aspiration for karyotype
88
Describe Hemophilia *
- Bleeding disorders caused by mutations in genes that code for coagulation proteins
- Mutation on F8 or F9 genes, located on the X chromosome
89
Compare Hemophilia A VS Hemophilia B *
- Mutation in F8 gene causes factor VIII deficiency
- Results in hemophilia A (classic hemophilia)
- More common
- Mutation in F9 gene causes factor IX deficiency
- Results in hemophilia B (Christmas Disease)
90
Describe Pattern of inheritance of Hemophilia *
- X-linked recessive pattern
- Genes associated are on the X chromosome
- Most people affected are males
91
Describe the 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 or surgery
- Severity of symptoms can be variable
92
Describe Sickle Cell Disease Pathophysiology *
- Atypical hemoglobin molecules (hemoglobin S)
- Distorts the red blood cell into a crescent shape
- Abnormally shaped RBCs break down prematurely
- Mutation on HBB gene
93
Describe Clinical manifestations of Sickle Cell Disease
- Anemia, infections, episodic pain
| - Shortness of breath, fatigue, delayed growth
94
Describe inheritance of Sickle Cell Disease *
- Autosomal recessive
- Most common in people whose ancestors came from Greece, Africa, Turkey, Italy, Arabian Peninsula, India, South America, Central America, Caribbean
95
Describe Cystic Fibrosis Pattern of inheritance *
- Autosomal recessive
| - Two copies of mutated gene are needed for disease to be expressed
96
Describe Genetic mutation of Cystic Fibrosis *
- Mutation in the CFTR gene (cystic fibrosis transmembrane conductance regulator)
- CFTR codes for a protein that regulates chloride channels in epithelial cells
- When mutated, a defective protein is made, causing a disruption of chloride and water transport - water balance in secretions is disrupted
97
Describe the Clinical manifestations of Cystic Fibrosis *
- Causes thick, sticky mucous obstructing airways in lungs and ducts in pancreas
- Can affect pancreas, intestines, GU tract, hepatobiliary system, and exocrine glands
98
Describe Symptoms of Cystic Fibrosis *
- Difficulty breathing, infections in lungs
- Problems with nutrient digestion
- Buildup of mucous prevents pancreatic enzymes from reaching intestine
- Failure to thrive, poor growth rate
- ***Meconium ileus*** – newborn intestinal obstruction due to thick fecal waste products
99
What is the most common morbidity associated with Cystic Fibrosis? *
- Pulmonary disease
- Pulmonary system can’t defend against pathogens well – leads to sinusitis and bronchitis
- Nasal polyps, nosebleeds, chronic sinus infections common in CF patients
- Thick mucous builds up in lower airways causing obstruction
100
Describe Other associated info of Cystic Fibrosis *
- Common genetic disease in the white population in the US
- Disease incidence: 1 in 3500 white newborns
- Carrier incidence: 1 in 25
- Most cases diagnosed by age 1
- Sweat chloride test – primary test for diagnosis
101
Describe the Sweat chloride test *
- Defective chloride channel doesn’t allow chloride to be reabsorbed
- Concentration of chloride in sweat is elevated in CF
- Genetic testing used to confirm results
102
Describe Marfan Syndrome *
- Autosomal dominant
- Results from either an inherited mutation or a new mutation of the fibrillin-1 gene (FBN1)
- Causes defects in connective tissue affecting multiple systems
- Bones
- Ligaments
- Muscles
- Blood vessels
- Heart valves
103
Describe 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
- Hyperflexible joints
- Chest deformities
104
Describe Key primary features of Marfan Syndrome *
***Dislocated lens of the eye – vision problems***
***Aortic aneurysm/dissection***
105
Describe Heart defects in Marfan Syndrome *
-Heart defects are major cause of morbidity and mortality
- Mitral valve prolapse, aortic valve regurgitation
- Both of these can cause SOB, fatigue, palpitations
106
Advice for people with Marfan Syndrome
Affected individuals are advised to avoid contact sports, caffeine, and decongestants due to increased stress placed on CV system
107
Describe Neurofibromatosis Type I *
- AKA von Recklinghausen disease
- Autosomal dominant
- Mutation on NF1 gene on chromosome 17
108
What is the NF1 gene on chromosome 17? What would you see in a mutation here? *
-Tumor suppressor gene
- Mutation results in:
- 1) Growth of neurofibromas - benign tumors that grow on nerves of skin and brain (Subcutaneous tumors)
- 2) Changes in skin pigmentation
- Café-au-lait spots
- Flat patches on skin darker than surrounding area
- Lisch nodules in iris
- Freckles in axillae and groin
109
Describe Diagnostic features for Neurofibromatosis Type I *
- 1.5 cm or larger café-au-lait spot post puberty or 6 or more café-au-lait spots 0.5 cm or larger in before puberty
- 2 or more neurofibromas
- Axillary or inguinal freckling (***Crowe sign***)
- Optic glioma
- 2 or more Lisch nodules
- 1st degree relative with NF1
110
Describe Polycystic Kidney Disease Pathophysiology
- Clusters of fluid filled sacs develop in kidneys
- Affects ability to filter the blood properly
- Kidneys become enlarged and can fail
111
Describe Polycystic Kidney Disease Clinical manifestations
- Hypertension
- Back pain
- Hematuria
- UTIs, kidney stones
112
Describe Other associations of Polycystic Kidney Disease
- Liver cysts
- Heart valve abnormalities
- Increased risk of aortic aneurysm and brain aneurysm
113
What are the two forms of Polycystic Kidney Disease
1) Autosomal dominant – sx start in adulthood
- 1 in 1000; PKD1 and PKD2 genes
- Usually inherited (90% of the time)
2) Autosomal recessive – rare, lethal early in life
- 1 in 30,000
- PKHD1 gene
114
Describe Congenital Abnormalities
- Approximately 10% of all newborns have some birth defect. Ranges from minor biochemical problem to severe physical deformity
- Caused by variety of biological, chemical, and physical agents
- Contributors: mutant genes, chromosomal defects, multifactorial components
- Biggest cause of birth defects: unknown etiology
115
What is Teratology?
-Study of abnormal development
116
What are Teratogens?
- Anything capable of disrupting embryonic or fetal development and producing malformations
- Critical period for teratogenic effects is 3-16 weeks’ gestation
- Timing of exposure determines which systems are affected
117
Newborn Screening
- Biochemical analysis that determines whether certain proteins (enzymes) are present or absent
- These are typically autosomal recessive conditions
- Referred to as “inborn errors of metabolism”
- Inherited defect in one or more enzymes
- Newborn screening checks for many of these metabolic disorders
- 1st test: baby is 24-36 hours old
- 2nd test: 1st office visit, between 5-10 days
Foundations EXAM 2
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