CHAPTER VI: A. GENETIC DISORDERS; B. CYTOGENETIC DISORDERS Flashcards
1
Q
Associated defects of Mendelian Disorders
A
- Marfan Syndrome
- Ehlers-Danlos Syndrome
2
Q
Associated with defects in receptor proteins
A
- Familial Hypercholesterolemia (FH)
3
Q
Associated with defects in enzymes
A
- Lysosomal Storage Diseases
- Tay-Sachs Disease
- Niemann-Pick Disease
- Gaucher’s Disease
- Mucopolysaccharidoses
- Glycogen Storage Diseases
- Alkaptonuria
4
Q
Associated with defects in proteins that regulate cell growth
A
- Neurofibromatosis
- Triplet Repeat Mutation Fragile X Syndrome
5
Q
- Neurofibromatosis
A
a) Multifactorial
b) Single Gene Disorders with non-classic inheritance
6
Q
CYTOGENETIC DISORDERS
A
a) Involving autosomes
b) Involving sex chromosomes
c) Mutations in Mitochondrial genes
7
Q
a) Involving autosomes
A
Trisomy 21
Trisomy 18
Trisomy 13
Cri-du-Chat
8
Q
b) Involving sex chromosomes
A
Klinefelter’s Syndrome
XYY Syndrome
Turner’s Syndrome
Hermaphroditism
Pseudohermaphroditism
9
Q
c) Mutations in Mitochondrial genes
A
Leber’s Hereditary Optic Neuropathy
Prader-Willi Syndrome
Angelman’s Syndrome
10
Q
Genomic Imprinting
A
Leber’s Hereditary Optic Neuropathy
11
Q
is a disease caused in whole or in part by a change in the DNA sequence away from the normal sequence.
A
Genetic disorder
12
Q
mutation in one gene
A
monogenic disorder
13
Q
mutations in multiple genes
A
multifactorial inheritance disorder
14
Q
disease caused by a combination of gene mutations and [?]
A
environmental factors
15
Q
disease caused by damage to chromosomes
A
changes in the number or structure of entire chromosomes, the structures that carry genes
16
Q
It is one of the most common inherited disorders of connective tissue.
A
Marfan Syndrome
17
Q
Autosomal dominant condition
A
Marfan Syndrome
18
Q
Cause: mutation in the FBN1 gene
A
Marfan Syndrome
19
Q
are associated with a broad continuum of physical features ranging from isolated features to a severe and rapidly progressive form in newborns.
A
FBN1 mutations
20
Q
Marfan Syndrome Symptoms
A
Bones
Heart
Lungs
Eyes
21
Q
Ehlers-Danlos Syndrome Signs and Symptoms
A
Musculoskeletal
Skin
Cardiovascular
Vascular skin conditions
Orthostatic intolerance, Dilation and/or rupture of ascending aorta, Cystic medial necrosis, Varicose veins
22
Q
Ehlers-Danlos Syndrome Other Signs and Symptoms
A
Orthostatic intolerance, Dilation and/or rupture of ascending aorta, Cystic medial necrosis, Varicose veins
23
Q
Hyper-flexible joints
A
Musculoskeletal
24
Q
Unstable joints that are prone to sprain, dislocation, subluxation and hyperextension
A
Musculoskeletal
25
osteoarthritis
Musculoskeletal
26
Chronic degenerative joint disease
Musculoskeletal
27
Swan neck deformity of the fingers
Musculoskeletal
28
Muscle fatigue that increases with use
Musculoskeletal
29
hypotonia in infancy
Musculoskeletal
30
Osteopenia
Musculoskeletal
31
Stretchy ligaments and tendons
Musculoskeletal
32
Tearing of tendons or muscles
Musculoskeletal
33
Deformities of the spine
Musculoskeletal
34
Myalgia and arthralgia
Musculoskeletal
35
Stretchy skin with a velvety texture
Skin
36
Fragile skin
Skin
37
Easy bruising
Skin
38
Abnormal wound healing and scar formation
Skin
39
Redundant skin folds
Skin
40
Molluscoid pseudotumors
Skin
41
Subcutaneous spheroids
Skin
42
Fatty growths on forearms or shins
Skin
43
Angioplasia
Skin
44
Fragile blood vessels
Cardiovascular
45
Life-threatening carotid-cavernous fistula
Cardiovascular
46
Unpredictable rupture of medium-sized arteries
Cardiovascular
47
Valvular heart disease
Cardiovascular
48
Raynaud's phenomenon
Vascular skin conditions
49
Livedo reticularis
Vascular skin conditions
50
Autosomal dominant
Classical 1 and 2
Vascular 4
51
Dominant/Recessive
Hypermobility 3
52
Tenascin- X def.
Hypermobility 3
53
Type 3 collagen
Vascular 4
54
Autosomal recessive
Kyphoscoliosis 6
Arthrochalasis 7A and 7B
55
Type 1 collagen
Arthrochalasis 7A and 7B
56
Lysyl hydroxylase def.
Kyphoscoliosis 6
57
COL5A1
Classical 1 and 2
58
COL5A2
Classical 1 and 2
59
COL1A1
Classical 1 and 2
Arthrochalasis 7A and 7B
60
COL3A1
Hypermobility 3
Vascular 4
61
TNX B
Hypermobility 3
62
PLOD1
Kyphoscoliosis 6
63
COL1A1
Arthrochalasis 7A and 7B
64
ADAMTS2
Dermatosparaxis C
65
abnormally longer than normal
Bones
66
dolichostenomelia
Bones
67
arachnodactyly
Bones
68
scoliosis
Bones
69
pectus excavatum
Bones
70
pectus carinatum
Bones
71
high palate
Bones
72
malocclusions
Bones
73
angina pectoris
Heart
74
tachycardia
Heart
75
cystic medial degeneration
Heart
76
aortic dissection
Heart
77
heart murmur
Heart
78
risk of spontaneous pneumothorax
Lungs
79
emphysema
Lungs
80
COPD
Lungs
81
collapsed lung
Lungs
82
sleep apnea
Lungs
83
myopia or hyperopia
Eyes
84
astigmatism
Eyes
85
glaucoma
Eyes
86
cataract
Eyes
87
detachment or tear in the retina
Eyes
88
An inherited condition that causes high levels of LDL cholesterol levels beginning at birth, and heart attacks at an early age.
Familial Hypercholesterolemia (FH)
89
It is caused by a defect on chromosome 19
Familial Hypercholesterolemia (FH)
90
The defect makes the body unable to remove low density lipoprotein from the blood.
Familial Hypercholesterolemia (FH)
91
This results in a high level of LDL in the blood
Familial Hypercholesterolemia (FH)
92
Familial Hypercholesterolemia (FH) Other names:
o Type II hyperlipoproteinemia;
o Hypercholesterolemic xanthomatosis;
o Low density lipoprotein receptor mutation
93
Fatty skin deposits over parts of the hands, elbows, knees, ankles and around the cornea of the eye
Familial Hypercholesterolemia (FH)
94
Fatty skin deposits
xanthomas
95
Cholesterol deposits in the eyelids
(xanthelasmas)
96
A physical exam may show fatty skin growths called xanthomas and cholesterol deposits in the eye.
Familial Hypercholesterolemia (FH)
97
cholesterol deposits in the eye
corneal arcus
98
A. Lateral borders of thickened [?] are shown with arrows.
Achilles' tendons
99
B: can also occur in the extensor tendons of the hands (shown), feet, elbows and knees.
Tendinous xanthomas
100
C: are cholesterol deposits in the eyelids.
Xanthelasmas
101
D: results from cholesterol infiltration around the corneal rim.
Arcus cornealis
102
Lysosomal Storage Diseases
1. Tay-Sachs Disease
2. Niemann-Pick Disease
3. Gaucher’s Disease
4. Mucopolysaccharidoses
5. Glycogen Storage Diseases
6. Alkaptonuria
103
The disease is named for Warren Tay, a British ophthalmologist who in 1881 described a patient with a cherry-red spot on the retina of the eye.
Tay-Sachs Disease
104
Life-threatening disease of the nervous system passed down through families.
Tay-Sachs Disease
105
occurs when the body lacks hexosaminidase A
Tay-Sachs Disease
106
caused by a defective gene on chromosome 15
Tay-Sachs Disease
107
When both parents carry the defective gene, a child has a 25% chance of developing the disease.
Tay-Sachs Disease
108
The child must receive two copies of the defective gene, one from each parent, in order to become sick
Tay-Sachs Disease
109
The disease is most common among the Ashkenazi
Tay-Sachs Disease
110
Jewish population.
Tay-Sachs Disease
111
Tay-Sachs Disease Other names
o GM2 gangliosidosis - Tay-Sachs;
o Lysosomal storage disease - TaySachs disease
112
Deafness
Tay-Sachs Disease
113
decreased eye contact
Tay-Sachs Disease
114
blindness
Tay-Sachs Disease
115
Decreased muscle tone (loss of muscle strength)
Tay-Sachs Disease
116
loss of motor skills
Tay-Sachs Disease
117
paralysis
Tay-Sachs Disease
118
Slow growth and delayed mental and social skills
Tay-Sachs Disease
119
Dementia (loss of brain function)
Tay-Sachs Disease
120
Increased startle reaction
Tay-Sachs Disease
121
Irritability
Tay-Sachs Disease
122
Seizures
Tay-Sachs Disease
123
an autosomal recessive genetic disorder
Tay-Sachs Disease
124
Autosomal means it affects males and females equally and recessive means both parents must be a carrier for the children to be at risk.
Tay-Sachs Disease
125
If both parents are carriers, there is a 25% chance with each pregnancy that the child will be affected.
Tay-Sachs Disease
126
A primary deficiency of acid sphingomyelinase and the resultant accumulation of sphingomyelin.
Niemann-Pick Disease
127
phagocytic cells of spleen, liver, bone, marrow, lymph nodes, lungs are enlarged and vacuolated as a result of the storage of lipids
Niemann-Pick Disease
128
stuffed with droplets or particles of the complex lipid, imparting a fine vacuolation or foaminess to the cytoplasm
Niemann-Pick Disease
129
manifests itself in infancy with massive visceromegaly and severe neurologic deterioration
Niemann-Pick Disease Type A or Classic infantile form
130
no neurologic disorders
Niemann-Pick Disease Type B Visceral juvenile form
131
most common form of the disease, subtype with brain complications into C1 and C2
Niemann-Pick Disease Type C Subacute/ Juvenile form
132
caused by the mutation in the same gene as type C1, was originally separated from type C to delineate a group of patients sharing a common ancestry with otherwise identical disorders, no longer used
Niemann-Pick Disease Type D Nova Scotian Type
133
o lipid histiocytosis
o neuronal cholesterol lipidosis
o neuronal lipidosis
o sphingomyelin lipidosis
o sphingomyelin/cholesterol lipidosis
o sphingomyelinase deficiency
Niemann-Pick Disease
134
Nova Scotian type
Niemann-Pick Disease Type D
135
rare genetic disorder that is one of a group called lysosomal storage disorders.
Gaucher’s Disease
136
It is an inherited disorder that results in the accumulation of fatty molecules called cerebrosides in the body's organs and tissues
Gaucher’s Disease
137
It is caused by a missing or deficient enzyme called 'glucocerebrosidase'
Gaucher’s Disease
138
the gene that would normally tell the body to produce this enzyme is altered
Gaucher’s Disease
139
Signs and Symptoms: enlarged liver and spleen, low platelet and hemoglobin counts, problems with bones and joints
Gaucher’s Disease
140
Liver and spleen enlargement (hepatosplenomegaly) can occur as the result of an inherited disorder in which the liver cannot process glucocerebroside
Gaucher’s disease
141
The buildup of this substance in body tissues can cause severe damage to the central nervous system in infants.
Gaucher’s disease
142
group of inherited lysosomal storage disorders
Mucopolysaccharidoses
143
abnormal accumulation of certain complex carbohydrates (glycosaminoglycans) in the arteries, skeleton, eyes, joints, ears, skin, and/or teeth.
Mucopolysaccharidoses
144
These accumulations may also be found in the respiratory system, liver, spleen, central nervous system, blood, and bone marrow.
Mucopolysaccharidoses
145
This accumulation eventually causes progressive damage to cells, tissues, and various organ systems of the body.
Mucopolysaccharidoses
146
Signs and symptoms: coarse facial features, short stature, heart abnormalities, breathing irregularities, liver and spleen enlargement (hepatosplenomegaly), and/or neurological abnormalities
Mucopolysaccharidoses
147
rare condition that changes the way the body uses and stores glycogen, a form of sugar or glucose
Glycogen Storage Diseases
148
is passed down from parents to children (is hereditary). It is most often seen in babies or young children. But some forms may appear in adults.
Glycogen Storage Diseases
149
von Gierke disease
Type I
150
Most common form of GSD
Type I
151
don't have the enzyme needed to turn glycogen into glucose in the liver
Type I
152
Glycogen builds up in the liver.
Type I
153
Symptoms often appear in babies around 3 to 4 months old.
Type I
154
They may include low blood sugar (hypoglycemia) and a swollen belly because of an enlarged liver
Type I
155
rare genetic metabolic disorder characterized by the accumulation of homogentisic acid in the body.
Alkaptonuria
156
Cause: mutation of the homogentisate 1,2dioxygenase (HGD) gene
Alkaptonuria
157
Inherited as an autosomal recessive trait
Alkaptonuria
158
Affected individuals lack enough functional levels of an enzyme required to breakdown homogentisic acid
Alkaptonuria
159
Affected individuals may have dark urine or urine that turns black when exposed to air.
Alkaptonuria
160
Dark/ Black urine upon long standing exposure to the air
Alkaptonuria
161
- connective tissue such as cartilage turns blue, grey or black due to the chronic accumulation of homogentisic acid
Alkaptonuria-Ochronosis
162
Whites of the eyes (sclera) also become discolored
Alkaptonuria
163
Tendonitis
Alkaptonuria
164
Arthritis and ochronotic arthropathy
Alkaptonuria
165
rare genetic disorder that causes typically benign tumors of the nerves and growths in other parts of the body
Neurofibromatosis
166
caused by mutations in the gene that controls production of a protein called neurofibromin
Neurofibromatosis type I (NF1)
167
manifests itself at birth or during early childhood
Neurofibromatosis type I (NF1)
168
manifests itself at birth or during early childhood
Neurofibromatosis type I (NF1)
169
results from mutations in a different tumor-suppressing gene (neurofibromin 2, merlin)
Neurofibromatosis type II (NF2)
170
may appear during childhood, adolescence or early adulthood
Neurofibromatosis type II (NF2)
171
characterized by benign tumors of the nerves that transmit sound impulses and balance signals from the inner ears to the brain
Neurofibromatosis type II (NF2)
172
more frequently diagnosed in adults aged 30 and older
Schwannomatosis
173
characterized by moderate intellectual disability in affected males and mild intellectual disability in affected females
Triplet Repeat Mutation – Fragile X Syndrome
174
caused by an abnormality (mutation) in the FMR1 gene
Triplet Repeat Mutation – Fragile X Syndrome
175
is a gene located on the X chromosome that produces a protein called FMRP needed for proper cell function
FMR1
176
large head, long face, prominent forehead and chin, protruding ears, loose joints and large testes
Triplet Repeat Mutation – Fragile X Syndrome
177
flat feet, frequent ear infections, low muscle tone, a long narrow face, high arched palate, dental problems, crossed eyes (strabismus) and heart problems including mitral valve prolapse
Triplet Repeat Mutation – Fragile X Syndrome
178
Discovered in 1966 by Langdon Down
Trisomy 21
179
It is the only human autosomal trisomy in which a significant number of individuals survive longer than a year past birth.
Trisomy 21
180
Mental retardation
Trisomy 21
181
Multiple physical abnormalities such as heart defects
Trisomy 21
182
affected children are small in stature because of delayed maturation of the skeletal system
Trisomy 21
183
Poor muscle tone resulting in a characteristic facial appearance
Trisomy 21
184
Shortened life span
Trisomy 21
185
Most cases are caused by non-disjunction
Downs syndrome
186
Failure of homologous chromosomes to separate in meiosis
non-disjunction
187
Nondisjunction of [?] is more likely to happen in oogenesis than in spermatogenesis, and so the abnormal gamete in Down syndrome is usually the egg
chromosome 21
188
Edwards Syndrome
Trisomy 18
189
Patau Syndrome
Trisomy 13
190
Rare conditions associated with major developmental abnormalities
Trisomy 18 (Edwards Syndrome) and Trisomy 13 (Patau Syndrome)
191
Affected infants can survive for only a few days or weeks.
Trisomy 18 (Edwards Syndrome) and Trisomy 13 (Patau Syndrome)
192
In 1960, Klaus Patau and his associated observed an infant with severe developmental malformations with a karyotype of 47 chromosomes
Trisomy 13
193
average survival: Less than six months
Trisomy 13
194
Majority are male
Trisomy 13
195
Affected infants are not mentally alert
Trisomy 13
196
Are thought to be deaf
Trisomy 13
197
Characteristically have a harelip, clef palate
Trisomy 13
198
Demonstrate polydactyly
Trisomy 13
199
Autopsy reveals congenital malformation of most organ systems
Trisomy 13
200
Condition indicative of abnormal developmental events occurring as early as 5-6 weeks of gestation.
Trisomy 13
201
In 1960, John H. Edwards and his colleagues reported on an infant trisomic for a chromosome in the E group
Trisomy 18
202
Survival: Less than 4 months
Trisomy 18
203
Symptoms: Congenital heart defects, growth retardation, dysmorphic features, facial clefts, spina bifida, severe developmental delay
Trisomy 18
204
Smaller than the average newborn
Trisomy 18
205
Skulls are elongated in an anterior-posterior direction
Trisomy 18
206
Ears are set low and malformed
Trisomy 18
207
Webbed neck
Trisomy 18
208
Congenital dislocation of hips
Trisomy 18
209
Receding chin
Trisomy 18
210
Due to a missing piece (deletion) of a specific part of chromosome 5 known as the 'p' arm.
Cri-du-Chat
211
In general, the severity of the symptoms is determined by the size and location of the deletion on chromosome 5.
Cri-du-Chat
212
This deletion occurs very early in the development of an embryo and cri du chat syndrome is usually not inherited in families.
Cri-du-Chat
213
present from birth and affects growth and development
Cri-du-Chat
214
Infants with this condition often have a high-pitched cat-like cry, small head size, and a characteristic facial appearance.
Cri-du-Chat
215
Cat-like cry
Cri-du-Chat
216
Small head size (microcephaly)
Cri-du-Chat
217
Characteristic facial features
Cri-du-Chat
218
Hypotonia
Cri-du-Chat
219
Intellectual disability
Cri-du-Chat
220
Global developmental delay
Cri-du-Chat
221
Behavior issues
Cri-du-Chat
222
Growth delay
Cri-du-Chat
223
Diagnosis: based on the clinical examination, symptoms and confirmed by the results of genetic testing.
Cri-du-Chat
224
Treatment is focused on managing the symptoms.
Cri-du-Chat
225
47, XXY
Klinefelter’s Syndrome
226
Males
Klinefelter’s Syndrome
227
Tall, do not undergo normal sexual maturation, are sterile, and in some cases have enlargement of the breasts.
Klinefelter’s Syndrome
228
Mild mental impairment is common
Klinefelter’s Syndrome
229
rare chromosomal disorder that affects males. It is caused by the presence of an extra Y chromosome.
XYY Syndrome
230
Affected individuals are usually very tall.
XYY Syndrome
231
Many experience severe acne during adolescence.
XYY Syndrome
232
Additional symptoms may include learning disabilities and behavioral problems such as impulsivity.
XYY Syndrome
233
Intelligence is usually in the normal range, although IQ is on average 10-15 points lower than siblings.
XYY Syndrome
234
Synonyms of XYY
XYY Syndrome
235
47, XYY
XYY Syndrome
236
Jacob's syndrome
XYY Syndrome
237
XYY karyotype
XYY Syndrome
238
YY syndrome
XYY Syndrome
239
45, X
Turner’s Syndrome
240
Monosomy of the X chromosome in females
Turner’s Syndrome
241
Phenotypically female but are short in stature and do not exhibit sexual maturation.
Turner’s Syndrome
242
Mental abilities are typically within the normal range.
Turner’s Syndrome
243
the condition of having both male and female reproductive organs
Hermaphroditism
244
Conditions that involve discrepancies between external genitalia and internal reproductive organs are described by the term intersex.
Hermaphroditism
245
Intersex conditions are sometimes referred to as disorders of sexual development (DSDs).
Hermaphroditism
246
True gonadal intersex or True hermaphroditism- individual has both ovarian and testicular tissue.
Hermaphroditism
247
The ovarian and testicular tissue may be separate, or the two may be combined in what is called an
ovotestis
248
Affected individuals have sex chromosomes showing male-female [?] (where one individual possesses both the male XY and female XX chromosome pairs).
mosaicism
249
a condition in which the individual has a single chromosomal and gonadal sex but combines features of both sexes in the external genitalia, causing doubt as to the true sex.
Pseudohermaphroditism
250
refers to an individual with ovaries but with secondary sexual characteristics or external genitalia resembling those of a male
Female pseudohermaphroditism
251
also known as adrenogenital syndrome, is a common cause of female pseudohermaphroditism.
Congenital adrenal hyperplasia
252
refers to individuals whose gonads are testes but whose secondary sexual characteristics or external genitalia resemble those of a female.
Male pseudohermaphroditism
253
is rare and almost always results from autosomal recessive genetic defects (defects that must be inherited from both parents in order to be expressed).
Male pseudohermaphroditism
254
condition characterized by vision loss. Vision loss is typically the only symptom of LHON
Leber’s Hereditary Optic Neuropathy
255
characterized by bilateral, painless, and almost sudden vision failure that develops in young adulthood (around 20 to 30 years of age).
Leber’s Hereditary Optic Neuropathy
256
Blurring and clouding of vision (usually the first symptoms) affecting the central visual field
Leber’s Hereditary Optic Neuropathy
257
Severe loss of visual acuity (sharpness of vision) and color vision over time
Leber’s Hereditary Optic Neuropathy
258
Loss of ability to complete visual tasks such as reading, driving, and recognizing faces
Leber’s Hereditary Optic Neuropathy
259
A growing, dense central scotoma (blind spot) seen during visual field testing
Leber’s Hereditary Optic Neuropathy
260
Development of optic atrophy
Leber’s Hereditary Optic Neuropathy
261
are genetic disorder that results in a number of physical, mental and behavioral problems.
Prader-Willi Syndrome
262
Caused by a defect on chromosome 15 disrupts the normal functions of the hypothalamus
Prader-Willi Syndrome
263
A key feature of Prader-Willi syndrome is a constant sense of hunger that usually begins at about 2 years of age.
Prader-Willi Syndrome
264
Infants: Poor muscle tone, Distinct facial features, Poor sucking reflex, Generally poor responsiveness, Underdeveloped genitals
Prader-Willi Syndrome
265
Early childhood to adulthood: Food craving and weight gain, Underdeveloped sex organs, Poor growth and physical development, Cognitive impairment, Delayed motor development, Speech problems, Behavioral problems, Sleep disorders.
Prader-Willi Syndrome
266
rare genetic and neurological disorder characterized by severe developmental delay and learning disabilities
Angelman’s Syndrome
267
absence or near absence of speech
Angelman’s Syndrome
268
inability to coordinate voluntary movements (ataxia)
Angelman’s Syndrome
269
tremulousness with jerky movements of the arms and legs and a distinct behavioral pattern characterized by a happy disposition and unprovoked episodes of laughter and smiling
Angelman’s Syndrome
270
Ataxia
Angelman’s Syndrome
271
hold their arms up with the wrists and elbows bent and may flap their hands repeatedly when walking or excited
Angelman’s Syndrome
272
hypotonia of the trunk
Angelman’s Syndrome
273
hypertonia of the arms and legs
Angelman’s Syndrome
274
hyperreflexia
Angelman’s Syndrome
275
unprovoked, prolonged laughter and smiling
Angelman’s Syndrome
276
easily excited, hypermotoric and hyperactive
Angelman’s Syndrome
