1
Q
Genome
A
Organism’s genetic material
2
Q
Gene
A
Set of nucleotides
3
Q
Genes instruct for
A
Protein synthesis
4
Q
Basic unit of inheritance
A
Gene
5
Q
Allele
A
Alternative form of gene
6
Q
Hereditary
A
Transmitted to offspring
7
Q
Hereditary aka
A
Familial
Genetic
8
Q
Perinatal
A
Last tri and 1st month after birth
9
Q
Neonate
A
First 4 weeks
10
Q
Infant
A
First year after birth
11
Q
Congenital
A
Present at birth
12
Q
4 categories of genetic disorders
A
- Single gene mutations
- Multifactorial inheritance
- Chromosomal abnormalities
- Atypical inheritance
13
Q
8% of pediatric hospitalizations
A
Single gene disorders
14
Q
3 types of single gene disorders
A
Autosomal dominant
Autosomal recessive
X-linked recessive
15
Q
5 MC autosomal dominant disorders
A
- Familial hypercholesterolemia
- Polycystic kidney disease
- Hereditary spherocytosis
- Marfan syndrome
- Huntington syndrome
16
Q
5 MC autosomal recessive disorders
A
- Sickle cell anemia
- Cystic fibrosis
- Tay-Sachs disease
- PKU
- Glycogen storage Disease
17
Q
2 MC X-linked diseases
A
Duchesse muscular Dystrophy
Hemophilia A
18
Q
Autosomal dominate has a ____ onset
A
Delayed
19
Q
___ can cause spontaneous condition in regards to autosomal dominate disorders
A
Sporadic mutations
20
Q
Autosomal dominant affects
A
Structural proteins
Membrane receptors
21
Q
Autosomal dominant can display ____ and ____
A
Reduced penetrance
Variable expressivity
22
Q
Reduced penetrance
A
Have mutation, but no physical manifestations
23
Q
Variable expressivity
A
Same mutation expressed differently in individuals
24
Q
Example of variable expressivity
A
Nevus vs cutaneous neurofibromas
25
Largest group of Mendelian disorders
Autosomal recessive
26
Autosomal recessive has ___ onset and ____
Early
Complete penetrance
27
Autosomal recessive is rarely
Sporadic
28
Autosomal recessive disrupts enzymes, causing
Altered metabolism
29
X-linked recessive, ___ are asymptomatic carriers and ___ have 50% chance of getting it
Females
Males
30
Multifactorial inheritance
Genetic + environmental risks
31
Marfan syndrome is
Autosomal dominant
32
Marfan syndrome results from mutation in ___ and is ____ familial and ___ sporadic
FBN1 mutation (fibrillin 1 gene)
85%
15%
33
Fibrillin
Structural glycoprotein made from fibroblasts
34
The disorder of fibrillin in marfan results in
Irregular CT
35
Bilateral lens subluxations aka
Ectopia lentis
36
Atlantoaxial instability and basilar invagination is observed in ____ patients with marfan syndome
30-50%
37
Wrist sign observed in Marfans
Thumb/index fingers overlap when wrapped around wrist
38
Steinberg Sign observed in Marfans
Adduction of thumb past 5th digit
39
Protrusio acetabuli observed in Marfans
Acetabulum protrudes medially
40
Thoracolumbar scoliosis observed in Marfans
>20 degrees lateral curve
41
Dolichocephaly
Elongated face
42
Dural ectasia observed in Marfans
Scalloping of dorsal vertebral body due to widening of Spinal canal
60-90% of patients
43
Symptoms of Marfan’s Syndrome
1. Ectopia lentis
2. Ruptured aorta
3. Floppy valve syndrome
4. Atlantoaxial instability and basilar invagination
5. Long limbs
6. Arachnodactyly
7. Pectus deformities
8. Wrist sign
9. Steinberg sign
10. Protrusio acetabuli
11. Pes planovalgus
12. Dolichocephaly
13. High arched dental palate
14. Dural ectasia
44
Ehlers Danlos Syndrome is
Autosomal dominant
1/200,000
45
Ehlers danlos syndrome is a defect in ___, which decreases tensile strength
Collagen
46
Symptoms of ehlers danlos syndrome
Hyperextensible skin
Hyper mobile joints
47
Familial hypercholesterolemia is
Autosomal dominant
1/500
48
Heterozygous familial hypercholesterolemia is a ____ increase in LDL, and has a ___ onset
2-3X
Adulthood
49
Xanthomas
Cholesterol deposits on tendons
50
Homozygous familial hypercholesterolemia is a ___ increase in LDL and has a ___ onset
5X
Childhood
51
More serious, and often lethal, familial hypercholesterolemia
Homozygous
52
Familial hypercholesterolemia is due to a mutated
LDLR gene
53
Mutated LDLR gene causes impaired ___, which increases ____ and ____
LDL Transport and catabolism
LDL in plasma
Vascular deposits
54
Treatment for familial hypercholesterolemia
Statins
| Lifestyle modifications
55
Cystic fibrosis is
Autosomal recessive
1/3200 Caucasians
56
____ is mutated in CF
CFTR gene
57
Mutated CFTR gene causes ____ Transport
Low Cl ion transport
58
Low Cl transport can result in
Viscous secretions
Salty sweat
59
MC cause of death in CF
Cor pulmonale
60
Cor pulmonale
R sided heart failure due to lungs
61
___ also common in CF
Pancreatic insufficiency
62
Males with CF can be infertile due to
Absent vas deferens
63
Chronic lung infections in CF due to
Low mucociliary clearance
64
Pancreatic insufficiency in CF due to
Ductal obstruction
65
Fibrillin is a component of
Microfibrils of ECM
66
Marfan’s syndrome most likely to affect 3 tissue types
Osseous skeletal tissue
Eyes
Cardiovascular tissue
67
Floppy valve syndrome MC in
Mitral valve
68
MC autosomal dominant Mendelian disorder
Familial hypercholesterolemia
69
Risks of familial hypercholesterolemia
Premature atherosclerotic plaques
Coronary artery disease
MI risk
70
Ductal obstruction in pancreas from CF prevents ___ resulting in ____
Pancreatic zymogens from reaching small intestine
Malabsorption
71
PKU is ____ and how common
Autosomal recessive
1/10,000
72
Main problem with PKU
Mutated phenylalanine hydroxylase
Can’t metabolize phenylalanine
73
People with PKU have light skin and hair pigmentation due to
Lack of tyrosine, which is precursor to melanin
74
Phenylalanine can be ___ if not metabolized
Neurotoxic
75
___ of people with PKU never talk, and ___ never walk
2/3
1/3
76
Maternal PKU
Mother with PKU must modify diet before conception to prevent microcephaly or cardiac malformations since phenylalanine crosses placenta and is teratogenic
77
Benign hyperphenylalanine
Modest PKU
No neurological damage
78
Alkaptonuria (AKU) aka
Black urine disease
79
AKU is
Autosomal recessive
80
AKU is a mutation in
Homogentisic oxidase
81
People with AKU have an inability to metabolize ____ and ___, causing ___ to accumulate
Tyrosine and phenylalanine
Homogentisic acid
82
Symptoms of AKU
Dark urine
Bark blue or black CT
Arthritis in joints
Destruction of heart valves
83
Galactosemia is
Autosomal recessive
84
Galactosemia is due to
GALT mutation
85
GALT
Galactose-1-phosphate-uridyltransferase
86
___ and ___ accumulates in galactosemia
Galactose and galactose -1-phosphate
87
Symptoms of galactosemia
```
Failure to thrive
Neuronal and liver damage
Cataracts
Vomiting
Diarrhea
Poor weight gain
```
88
Treatment for galactosemia
Discontinue lactose
Restrict lactose in first 2 years
89
Lysosomal Storage Diseases (LSD) are
Autosomal recessive
90
LSDs result in excessive storage of metabolites due to
Lack of lysosomal catabolism
91
PKU most common in
Scandinavian descent
92
Distinct sign of PKU
Musty or mousy urine odor
93
Ochronosis
Dark pigments in CT
94
Features of Lysosomal Storage Diseases
Early onset
CNS damage
Hepatosplenomegaly
Cellular dysfunction, often fatal
95
Types of LSD
1. Tay- Sachs
2. Gaucher
3. Mucopolysaccharidosis
96
Types of mucopolysaccaridosis
1. Hurler
| 2. Hunter
97
Tay-Sachs has mutated ___, resulting in ___ accumulated in brain/spinal cord
Hexosaminidase A enzyme
Gangliosides
98
____ are 1 in 30 carriers for Tay-Sachs
Ashkenazi Jews
99
Symptoms of Tay-Sachs
Intellectual disability
Flaccidity
Cherry red central macula
100
Treatment for Tay-Sachs
NONE
101
Gaucher Disease has mutated ___, resulting in ____ accumulating
Glucocerebrosidase gene
Glucocerebrosides
102
Treatment for Gaucher Disease
Lifeline enzyme replacement therapy
103
Type 1 Gaucher Disease
MC
Less severe
Ashkenazi Jews
104
Type 2 and 3 Gaucher Disease
More severe
| Neuro disturbances
105
Distinct characteristics of Gaucher Disease
Wrinkled tissue paper cytoplasm
Erlenmeyer flask deformity
106
Gaucher Disease
Low RBC = ___
Low WBC = ____
Low platelets = ____
Anemia; fatigue
Infections
Bruising
107
Mucopolysaccharidosis (MPS) deficiency in ___, causing ___ to accumulate
ECM breakdown enzymes
GAGS
108
Signs of MPS
```
Intellectual disability
Gargoylism
Arterial deposits
Clouding of cornea
Hepatosplenomegaly
```
109
Hurler syndrome inheritance
Auto. Recessive
110
Hurler syndrome deficiency
Alpha -L-iduronidase
111
Lethal by age 6-10
Hurler syndrome
112
Hurler syndrome is ____ severe than hunter syndrome
More
113
Hunter syndrome inheritance
X-linked
114
Hunter syndrome deficiency
L-iduronate sulfatase
115
___ and ___ accumulate in both Hurler and Hunter Syndrome
Heparan sulfate
| Dermatan sulfate
116
Glycogen storage diseases are due to suppressed ____, causing ___ to accumulate
Glycogen catabolism
Glycogen
117
Glycogen storage Disease inheritance
Autosomal recessive
118
Types of glycogen storage Disease
1. Von Gierke Disease
2. McArdle Disease
3. Pompe disease
119
Von Gierke Disease causes decreased
Liver glycolysis
120
Glycogen storage Disease
Von Gierke = ___
McArdle disease = ___
Hepatic
Myopathic
121
Deficiency in Von Gierke Disease
Glucose 6 phosphatase
122
McArdle Disease deficiency
Muscle phosphorylase
123
McArdle Disease can result in
Rhabdomyolysis
124
Pompe Disease deficiency
Lysosomal acid maltase
125
Pompe Disease lethal by
Age 2
126
Rhabdomyolysis
Rapid skeletal muscle destruction
127
Signs of rhabdomyolysis
```
Muscle pain
Myoglobinuria
Confusion
Weakness
Renal failure
```
128
Combined frequency of LSD
1 in 5,000
129
Type 1 Gaucher Disease aka
Chronic neuronopathic form
130
Type ___ is more severe than type ___ (Gaucher Disease)
2; 3
131
Gaucher Disease types 2 and 3 at risk for developing
Parkinson’s disease
132
Gaucher cells
Glucocerebrosides accumulation in macrophages
133
People with Von Gierke Disease predisposed for developing
Gout
Xanthomas of skin
Bleeding tendencies
134
Rhabdomyolysis can be due to
Trauma
| Intense physical exercise
135
MC cause of death in rhabdomyolysis
Renal failure due to myoglobin obstructing glomeruli
Gen Path
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