~80 Genetic Disorders Flashcards
1
Q
Inheritance 1p36.3
A
Sporadic
2
Q
3 major clinical features 1p36.3
A
Neurodev disabilities, characteristic face (straight eyebrows, deep-set eyes), hypotonia
3
Q
Inheritance Achondroplasia
A
AD
4
Q
Gene Achondroplasia
A
FGFR3
5
Q
3 major clinical features Achondroplasia
A
Rhizomelic limb shortening, macrocephaly, trident hands
6
Q
Characteristic Face Achondroplasia
A
Frontal bossing, Midface hypoplasia
7
Q
Inheritance Alagille
A
AD
8
Q
5 ‘organ’ systems affected in Alagille
A
Liver, Heart, Eyes, Skeleton, Face
9
Q
4 major clinical features Alagille
A
Bile duct paucity, pulmonic stenosis, posterior embryotoxon, butterfly-shaped vertebrae
10
Q
Inheritance ALS
A
Most sporadic (or AD, AR, XL)
11
Q
3 major clinical features of ALS
A
Asymmetric limb weakness, bulbar symptoms, muscle atrophy
12
Q
Inheritance Angelman Syndrome
A
Imprinted (loss of maternal copy)
13
Q
Etiologies for Angelman Syndrom
A
Del mat, pat UPD, loss UBE3A gene
14
Q
3 major features of Angelman Syndrome
A
Severe ID with speech problems, ataxia gait, happy/excitable/laughter
15
Q
Inheritance for Ataxia Telangiectasia
A
AR
16
Q
Hallmark in blood of Ataxia Telangiectasia
A
Elevated AFP
17
Q
3 major clinical features of A-T
A
Ataxia (before 5), telangiectasis in eyes and skin, increased risk of leukaemia and lymphoma
18
Q
Inheritance of Ataxia w/ Oculomotor Apraxia
A
AR
19
Q
3 major clinical features of Ataxia with Oculomotor Apraxia
A
Ataxia, Oculomotor Apraxia, Neuropathy, Chorea
20
Q
Inheritance of Bardet-Biedl Syndrome
A
AR
21
Q
3 major features of Bardet-Biedl Syndrom
A
Vision problems, obesity, ID, genital anomalies and anosmia
22
Q
Inheritance of BMD
A
xlr
23
Q
3 major clinical features of BMD
A
Muscle weakness, cardiomyopathy, may live into 40s
24
Q
Inheritance of BWS
A
AD (imprinting)
25
Etiologies for BWS
Imprinting of chromosome 11, paternal UPD of chromosome 11, mutations in CDKN1C
26
5 clinical features of BWS
Macrosomia, Macroglossia, visceromegaly, hemihyperplasia, abdominal wall defect
27
Increased risk for what kind of cancer in BWS
Wilm's Tumor and hepatoblastoma
28
Inheritance of BOR Syndrome
AD
29
3 major features of BOR Syndrome
Branchial arch anomalies, ear anomalies with HL, kidney anomalies
30
Inheritance of CADASIL
AD
31
3 major features of CADASIL
Migraine with aura, ischemic strokes and TIA, mood/cognitive problems
32
Inheritance of Canavan Disease
AR
33
Canavan can be characterized as?
Leukodystrophy
34
3 major features Canavan
No motor skills, feed/swallowing problems, seizures, sleep problems
35
Inheritance Cardio-Facial-Cutaneous Syndrome
AD
36
3 major features of Cardio-Facial-Cutaneous Syndrome
Heart- Pulmonic stenosis, characteristic face, Skin- wirnkled palms/soles
37
Inheritance of CMT
AD, AR, XL, Mt
38
3 major features of CMT1A
Toe walking, clumsy, foot deformities
39
Severity of CMT2A compared to CMT1A
CMT2A is more severe- earlier onset and require wheelchair
40
Inheritance of CHARGE syndrome
AD
41
CHARGE stands for what features?
Coloboma, Heart defect, Atresia Choanal, Retarded growth, Genital abnormalities, Ear abnormalities
42
Inheritance Cleidocranial Dysplasia
AD
43
3 major features of Cleidocranial dysplasia
Bone- absent clavicles, unusually shaped teeth, dysmorphic face
44
Inheritance Cockayne Syndrome
AR
45
3 major features of Cockayne Syndrome
Microcephaly, photosensitivity, FTT
46
People with Cockyne Syndrome have life threatening allergy to?
Metronidazole (antibiotic)
47
Inheritance Coffin-Lowry Syndrome
XLD
48
What sex is Coffin-Lowry syndrome more severe in?
Males
49
3 major features of Coffin-Lowry syndrome?
Profound ID, characteristic face, stimulus-induced drop episodes
50
Inheritance Cornelia de Lange Syndrome
AD
51
3 major features of Cornelia de Lange Syndrome
Short stature, abnormalities of bones in arms, ID/behavior problems, characteristic face
52
Inheritance of Costello Syndrome
AD (mostly de novo)
53
3 major features of Costello Syndrome
Development problems (FTT, DD), Heart problems (HCM), Characteristic face (curly/sparse hair)
54
People with Costello syndrome have risk for what kind of tumor
Rhabdomyosarcoma or neuroblastoma
55
Inheritance of Cri du Chat
Sporadic (usually)
56
Deletion in Cri du Chat is where?
5p
57
3 major features of Cri du Chat
High-pitched/cat-like cry, microcephaly, low birth weight
58
Inheritance of 22q11
Usually de novo
59
Where is deletion in 22q11?
22q11
60
3 major features of 22q11
Velopharyngeal incompetence, CHD, immune deficiency, increased risk for psych problems
61
Inheritance of DMD
XLR
62
3 major features of DMD
Muscle weakness and wasting-- wheelchair by adolescence, cardiomyopathy, live into 20s
63
Inheritance of early-onset Alzheimer's Disease
AD
64
3 major features of early-onset AD
Forgetfulness that interferes with daily life, needing help with personal care, may be personality/behaviour changes
65
Inheritance of Classic EDS
AD
66
3 major features of Classic EDS
Skin hyper extensibility, widened atrophic scars, joint hypermobility
67
Inheritance of hypermobile EDS
AD
68
3 major features of hypermobile EDS
Joint hyper mobility (complain of chronic pain), soft skin, absence of fragility
69
Inheritance of Vascular EDS
AD
70
3 major features of Vascular EDS
Arterial aneurysms, intestinal rupture, uterine rupture during pregnancy
71
Inheritance of Factor V Leiden Deficiency
Number of mutations influences risk
72
Inheritance of Familial Dysautonomia
AR
73
Unique features in Familial dysautonomia
Infancy- lack of tears, difficulty maintaining body temp; Kids- hold breath for long time; School age- bed wetting, reduced sensitivity to temperature changes/pain, BP regulation problems; Adult- walking problems, impaired kidney function
74
Inheritance of Crouzon Syndrome
AD
75
Inheritance of Apert Syndrome
AD
76
Inheritance of Pfeiffer Syndrome
AD
77
Inheritance of Muenke Syndrome
AD
78
3 major clinical features of Crouzon syndrome
Vrachycephaly, cervical spine anomalies, mild shortening of humerus/femora
79
2 major clinical features of Apert Syndrome
Brachycephaly, Mitten-type syndactyly of hands and feet
80
1 major clinical feature of Pfeiffer syndrome
Broad/angulated thumbs and great toes (also type 2- cloverleaf skull)
81
3 major features of Meunke Syndrome
Coronal synostosis, anomalies of hands and feet, hearing loss
82
Inheritance of Fragile X syndrome
XLR
83
Anticipation in Fragile X syndrome when passed through what parent?
Mom
84
3 major features of Fragile X
DD/ID, behaviour problems, dysmorphic face
85
Risks to Fragile X permutation carriers
FXTAS, POI
86
Premutation repeat number in Fragile X
55-200
87
Full mutation repeat number in Fragile X
200+
88
What trinucleotide repeat is expanded in Fragile X?
CGG
89
Inheritance of Friedreich's Ataxia
AR
90
3 major features of Friedreich's Ataxia
Ataxia, HCM, DM, scoliosis
91
What trinucleotide repeat is expanded in Friedreich's ataxia
GAA
92
Premutation repeat number in Friedreich's Ataxia
34-65
93
Full mutation repeat number in Friedreich's Ataxia
66-1300
94
Inheritance of Hereditary Hemorrhagic Telangiectasia
AD
95
3 major features of HHT
Arteriovenous malformations, mucocutaneous telangiectasis, frequent nosebleeds
96
Inheritance of Hereditary Neuropathy with Liability to Pressure Palsies
AD
97
3 major features of HNLPP
Recurrent episodes of numbers, pain in limbs, carpal tunnel syndrome
98
Inheritance of HD
AD
99
Anticipation occurs in HD when passed through which parent?
Dad
100
3 major features of HD
Psych, Motor- chorea, Cognitive
101
Premutation repeat number in HD
27-35
102
Full mutation repeat number in HD
40+
103
What trinucleotide repeat is expanded in HD
CAG
104
Inheritance Incontinentia Pigmenti
XLD (lethal in males)
105
4 stages of skin problems in Incontinentia Pigmenti
Vesicular-- verrucous-- pigmentary-- atrophic
106
Inheritance of Joubert Syndrome
AR (rarely XL)
107
3 major features of Joubert Syndrome
Molar tooth sign on MRI, episodes of usually fast/slow breathing, ataxia
108
Inheritance of Kabuki Syndrome
AD, XL
109
3 major features of Kabuki syndrome
DD, problems with hip/knee joints, Cleft palate, prominent finger pads
110
Inheritance of Kallman Syndrome
XL
111
3 major features of Kallman syndrome
Delayed/absent puberty, hypogonadotropic hypogonadism, anosmia
112
Karyotype of Klinefelter Syndrome
47, XXY
113
3 major features of Klinefelter Syndrome
Small testes, taller than peers, LD, behaviour problems
114
Inheritance of Krabbe Disease
AR
115
Enzyme deficiency in Krabbe disease
B-galactocerebrosidase
116
3 stages of features in infantile Krabbe
1: irritability/spasticity/FTT/dev arrest; 2: neurogeneration/seizures; 3: blind/deaf/unaware
117
Inheritance of Leber Hereditary Optic Neuropathy
mitochondrial
118
Major feature of LHON
Blurred/cloudy vision
119
Inheritance of LEOPARD Syndrome
AD
120
What does each letter stand for in LEOPARD Syndrome
Lentigines, Electrocardiographic conduction defects, Ocular hyperelorism, Pulmonary Stenosis, Abnormalities of Genitalia, Retarded growth, Deafness
121
Inheritance of Limb-Girdle Muscular Dystrophy
AR
122
3 major features of Limb Girdle Muscular Dystrophy
Weak thigh muscles, hypertrophy of calf muscles, cardiomyopathy in some
123
Loeys Dietz Inheritance
AD
124
3 major features of Loeys Dietz
Enlargement of aorta, arterial tortuosity, skeletal abnormalities, skin differences
125
Annual colonoscopy in Lynch syndrome to start at what age?
20-25 yo
126
Inheritance of Marfan Syndrome
AD
127
3 major features of Marfan Syndrome
Tall w/ arachnodactyly, ectopic lentil, aortic aneurysm
128
Inheritance of McCune Albright Syndrome
Not inherited-mosaicism
129
3 major features of McCune Albright Syndrome
Bone- polyostotic fibrous dysplasia, Skin- CALs with irregular borders, Endocrine- early puberty, thyroid goiter, acromegaly
130
Inheritance of Myotonic Dystrophy
AD
131
What trinucleotide repeat is expanded in Myotonic dystrophy
CTG
132
Premutation repeat number in Myotonic Dystrophy
35-49
133
Full mutation repeat number in myotonic dystrophy
\>50
134
3 major clinical features of myotonic dystrophy
Progressive muscle weakness/wasting, cataracts, cardiac conduction defects
135
Inheritance of Nemalin Myopathy
AR (less often AD)
136
3 major features of Nemalin Myopathy
Myopathy of proximal muscles, feeding/swallowing problems, joint contractures
137
Inheritance of NF1
AD
138
6 major features of NF1
CALs, neurofibromas, inguinal/axillary freckling, optic glioma, Lisch nodules, distinct osseous lesion
139
Inheritance of NF2
AD
140
NF2 has growth of non-cancerous tutors, especially:
Vestibular schwannomas or acoustic neuromas
141
Inheritance of Noonan Syndrome
AD
142
5 major features of Noonan Syndrome
Short stature, heart defect- pulmonic stenosis, bleeding problems, skeletal malformations, males with delayed puberty
143
People with Noonan syndrome are at increased risk for what type of cancer
Leukemia
144
Inheritance of Parkinson's disease
Sporadic (or AD or AR)
145
3 major features of Parkinson's disease
Tremor, rigidity, braykinesia (can have psych conditions)
146
What gene is a risk factor for (but is not independently responsible for) Parkinson's disease
LRRK2
147
Inheritance of Prayer Willi Syndrome
Sporadic
148
Where is deletion in Prader Willi Syndrome?
15p11-13
149
Etiologies for Prader Willi Syndrome?
Del of paternal 15p or maternal UPD of chromosome 15
150
3 major features of PWS
Intantile hypotonia and FTT, hyperphagia and obesity, hypogonadism
151
Inheritance of Cowden Syndrome
AD
152
Gene for Cowden Syndrome
PTEN
153
Increased risk for what cancers in Cowden syndrome?
Breast, endometrial, thyroid
154
Skin triad seen in Cowden syndrome
Facial trichillemommas, aural keratosis, papillomatous papules
155
Inheritance of Rett Syndrome
XLD (lethal in males)
156
3 major features of Rett syndrome
Developmental regression, hand wringing/clapping, seizures
157
Inheritance of Rubinstein-Taybi Syndrome
AD (most de novo)
158
3 major features of Rubinstein-Taybi Syndrome
ID, broad thumbs/first toes, eye/heart/kidney defects
159
People with Rubinstein-Taybi syndrome are at increased risk for what type of cancer?
Brain tumors, leukemia
160
Inheritance of Smith Magenis Syndrome
Sporadic
161
Where is deletion in Smith Magenis Syndrome
17p11.2
162
3 major features of Smith Magenis syndrome
DD/ID, Behaviour- self injury and lick/flip, sleep disturbances
163
Inheritance of Sotos Syndrome
AD (most de novo)
164
3 major features of Sotos Syndrome
Overgrowth in childhood, DD and behaviour problems, characteristic face
165
Inheritance of SMA
AR
166
3 major features of SMA
DD, unable to support head/sit unassisted, breathing and swallowing problems
167
What can modify the SMA phenotype?
Number of functional SMN2 copies
168
Inheritance of Syndromic Congenital Muscular Dystrophy
AR (sometimes AD)
169
3 major features of Syndromic Congenital Muscular Dystrophy
Muscle weakness at birth, delayed motor development with joint rigidity--\> joint contractors, spinal deformities, respiratory compromise
170
Inheritance of Tay Sachs Disease
AR
171
3 major features of Tay Sachs Disease
Loss motor skills, seizures/regression, die in early childhood
172
Gold standard for diagnosis of Tay Sachs
HEXA enzyme analysis
173
Inheritance of Triploidy
Sporadic
174
Karyotype for triploidy
69, XXX
175
Triploidy usually a result of extra paternal or maternal chromosomes?
Paternal
176
Signs in pregnant woman of triploidy fetus with extra paternal set
Cystic placenta, partial mole, IUGR, syndactyly
177
Signs in pregnant woman of triploidy fetus with extra maternal set
Small placenta, IUGR
178
Inheritance of T13
Usually sporadic
179
Karyotype for T13
47, XX, +13
180
3 major features of T13`
Midline defects: HPE, polydactyly, CL+P
181
Inheritance of T18
Usually sporadic
182
Karyotype of T18
47, XX, +18
183
3 major features of T18
Hypertonia, clenched fist with overlapping fingers, rocker bottom feet
184
Sign in pregnancy of T18 fetus
Polyhydramnios
185
Inheritance of T21
Usually sporadic (4% Rob)
186
Karyotype of T21
47, XX, +21
187
3 major features of T21
Hypotonia, CHD, characteristic face
188
Inheritance of Tuberous Sclerosis
AD
189
Organ systems affected in Tuberous Sclerosis
Skin, Kidney, Lung, Heart, Brain
190
4 skin findings in Tuberous Sclerosis
Ash leaf spots, shagreen patches, facial angiofibromas, inguinal fibromas
191
What is in brain of Tuberous Sclerosis patient and how does it affect phenotype
Cortical Tubers; the higher the number the higher the cognitive impairment
192
Inheritance of Turner Syndrome
Sporadic
193
Karyotype for Turner Syndrome
45, X
194
3 major features of Turner Syndrome
Short stature, gonadal dysgenesis, CHD in half
195
What treatment should be given to girls with Turner Syndrome
Estrogen replacement therapy
196
What treatment should be given to boys with Klinefelter syndrome
Testosterone supplementation
197
Inheritance of VACTERL Syndrome
Sporadic (sometimes multifactorial)
198
What does each letter in VACTERL stand for?
Certebral facts, Anal atresia, Cardiac facts, Tracheo-Esophageal fistula, Renal anomalies, Limb anomalies
199
Inheritance of VHL
AD
200
Gene in VHL
VHL
201
What is the lifetime risk of renal cancer in VHL?
40%
202
What cancers are at an increased risk in VHL?
Renal, hemangioblastoma, pheochromocytoma
203
Ophthalmology exams start at what age for screening for VHL?
5 yo
204
CNS imaging by MRI is annual in screening for VHL, starting at what age?
11 yo
205
Inheritance of Waardenburg Syndrome
AD
206
3 major features of Waardenburg syndrome
SNHL, partial albinism/white forelock, blue eyes (or Dif color)
207
Inheritance of William's Syndrome
Usually sporadic
208
Where is deletion in William's Syndrome
7q11.23
209
3 major features of William's Syndrome
Outgoing personality, Elfin face, Supravalvular aortic stenosis
210
Inheritance of Wilson's disease
AR
211
What substance accumulates in tissues in Wilson's disease
Copper
212
3 major features of Wilson's disease
Liver disease with jaundice, movement disorders, Kayser-Fleischer rings, psych symptoms
213
Inheritance of Wolf-Hirschhorn Syndrome
Sporadic
214
Where is deletion in Wolf-Hirschhorn syndrome?
4p16.3
215
3 major features of Wolf Hirschhorn Syndrome
Delayed growth and development, ID, Greek Warrior helmet
216
Inheritance of Xeroderma Pigmentosum
AR
217
2 major features of Xeroderma Pigmentosum
Extreme sensitivity to UV rays from sunlight, progressive neurologic abnormalities
218
People with Xeroderma Pigmentosum have increased risk for what type of cancer?
Skin
219
Smokers with Xeroderma Pigmentosum have increased risk for what type of cancer?
Brain and Lung
220
Inheritance of XL Adrenal Hypoplasia Congenita
XL
221
3 major features of XL Adrenal Hypoplasia Congenital
Adrenal insufficiency- vomiting, hypoglycaemia; hypogonadotropic hypogonadism
222
Inheritance of XL Adrenoleukodystrophy
XLR
223
Major features of Xl adrenoleukodystrophy
Males have initially normal dev--behavior/attention changes--problems in school-- loss of vision and comprehension, adrenocortical insufficiency
224
People with XL Adrenoleukodystrophy cannot metabolize?
Very long chain fatty acids (VLCFA)
225
Inheritance of WAGR syndrome
Sporadic
226
Genetic mutation in WAGR syndrome
Deletion of 11p
227
What does WAGR stand for?
Wilm's Tumor, Aniridia, GU anomalies, Retardation- ID
228
What does WAGRO stand for?
Wilm's Tumor, Aniridia, GU anomalies, Retardation- ID, Obesity
229
Inheritance of Kennedy's Disease
XLR
230
Mutation in Kennedy's Disease
CAG trinucleotide repeat expansion (\>35)
231
3 major features of Kennedy's Disease
Muscle weakness and wasting- cramps, difficulty walking, problems with feeding/swallowing; gynocomastia, infertility
232
Inheritance of Proteus syndrome
Not inherited- mosaic
233
3 major features of Proteus syndrome
Overgrowth, cerebriform connective tissue nevus on feet, ID, increased risk of pulmonary embolism
