Conditions Flashcards
(367 cards)
1
Q
Achondroplasia gene
A
FGFR3
2
Q
Achondroplasia inheritance
A
AD; 80% de novo
3
Q
Achondroplasia description
A
Rhizomelic shortening, macrocephaly, apnea, obesity, ear infections, genu verum (leg bowing), lordosis, kyphosis, spinal stenosis, hydrocephalus
Average lifespan
4
Q
Achondroplasia mutation(s)
A
GoF (constitutive activation) Two mutations: • c.1138G>A (p.Gly380Arg) • c.1138G>C (p.Gly380Arg) Penetrance 100%
5
Q
Hypochondroplasia gene
A
FGFR3 (~70%)
Potentially others too
6
Q
Hypochondroplasia inheritance
A
AD; majority de novo
7
Q
Hypochondroplasia description
A
Features similar to achondroplasia, but milder. Rhizo or meso.
May have mild ID
Average lifespan
8
Q
Thanatophoric Dysplasia gene
A
FGFR3
9
Q
Thanatophoric Dysplasia inheritance
A
AD; ~100% de novo
10
Q
Thanatophoric Dysplasia description
A
Micromelia, redundant skin, narrow chest, short ribs, under-developed lungs, macrocephaly, platyspondyly (flat vertebral bodies)
Type I: curved thigh bones
Type II: straight thigh bones and a moderate to severe cloverleaf skull
Typically lethal
11
Q
Campomelic Dysplasia gene
A
SOX9
12
Q
Campomelic Dysplasia inheritance
A
AD; most de novo
13
Q
Campomelic Dysplasia description
A
Short & bowed legs, dislocated hips, club feet, missing ribs, ambiguous genitalia, Pierre Robin.
Often lethal in infancy
14
Q
Diastrophic Dysplasia gene
A
SLC26A2
15
Q
Diastrophic Dysplasia inheritance
A
AR
16
Q
Diastrophic Dysplasia description
A
Short limbs, osteoarthritis, contractures, club foot, scoliosis, thumb abnormalities, cleft palate.
Typically live to adulthood
17
Q
SMA gene
A
SMN1, SMN2
18
Q
SMA inheritance
A
AR
19
Q
SMA description
A
Loss of lower motor neurons -> muscle atrophy
Proximal > distal progressive weakness, restrictive lung disease, joint contractures, scoliosis, tongue fasciculations (twitches). Types 0-IV correspond to # of SMN2 generally.
20
Q
SMN Testing
A
SMN1 exon 7 del/dup (up to 98% of cases), followed by SMN1 sequencing (2-5%)
21
Q
Charcot Marie Tooth gene
A
Many, including PMP22 (CMT1A)
22
Q
Charcot Marie Tooth inheritance
A
Type 1 & 2: AD
Type 4: AR
Many more forms, including X-linked
23
Q
Charcot Marie Tooth description
A
Peripheral nerve damage. Progressive distal weakness, foot drop, loss of sensory nerve function, shortened achilles, atrophy, contractures, hearing loss
24
Q
Charcot Marie Tooth Testing
A
Can start with PMP22 del/dup. Next, gene panel. Nerve conduction studies and nerve bx.
25
Dystrophinopathies gene
DMD
26
Dystrophinopathies inheritance
X-linked
| 1/3 de novo
27
Dystrophinopathies description
Proximal atrophy, DCM
28
Dystrophinopathies Testing
Elevated CK, molecular testing (del/dup then sequence)
29
Myotonic Dystrophy gene
Type I: DMPK
Type II: ZNF9
Both repeat expansion disorders
30
Myotonic Dystrophy inheritance
AD with anticipation
31
Myotonic Dystrophy description
Distal, diaphragm, neck, and face muscle weakness, cataracts, intellectual impairment, arrhythmia, cardiomyopathy, GI issues, balding, “pregnancy and gyn problems,” male infertility. Type II less severe.
32
Myotonic Dystrophy testing
PCR or Southern Blot
33
Facioscapulohumeral Muscular Dystrophy Gene
D4Z4
| Microsatellite contraction disorder
34
Facioscapulohumeral Muscular Dystrophy inheritance
AD
35
Facioscapulohumeral Muscular Dystrophy description
Muscle weakness of face, shoulders, upper arms. Other features: hearing loss, retinal telangiectasias
36
Emery-Dreifuss Muscular Dystrophy gene
Many, including EMD and LMNA
37
Emery-Dreifuss Muscular Dystrophy inheritance
Majority X-linked or AD
38
Emery-Dreifuss Muscular Dystrophy description
Weakness of shoulders, upper arms, calves; contractures in elbows, neck, ankles; conduction block in heart. Onset by 10y
39
Friedreich's Ataxia gene
FXN
| Repeat expansion disorder in nuclear mt gene
40
Friedreich's Ataxia inheritance
AR
41
Friedreich's Ataxia description
Impaired coordination, spasticity, arm/leg weakness, impaired hearing/speech/vision, hypertrophic cardiomyopathy. Onset typically 5-15y
42
Spinocerebellar Ataxia (SCA) Type I, II, III, etc. gene
ATXN1, ATXN2, ATXN3, etc. (CAG repeat)
43
Spinocerebellar Ataxia (SCA) Type I, II, III, etc. inheritance
AD; anticipation (paternal allele expansion)
44
Spinocerebellar Ataxia (SCA) Type I, II, III, etc. description
Progressive cerebellar ataxia, dysarthria, gait disturbance, slurred speech, difficulty with balance
45
Rett gene
MECP2
46
Rett inheritance
X-linked dominant
| Almost all de novo
47
Rett description
Almost exclusively females.
Onset: 6-18m
Loss/impairment of language, communication, coordination. Stereotypes hand movements. Abnormal breathing patterns. Seizure.
Life expectancy ~40s
48
MECP2 duplication syndrome inher.
x-linked
49
MECP2 duplication syndrome desc.
"Almost exclusively males.
| ID, hypotonia, seizures, respiratory tract infections."
50
Canavan gene
ASPA
51
Canavan inher.
AR
52
Canavan desc.
Leukodystrophy. Fail to meet early motor milestones, hypotonia, macrocephaly, seizures. Typically die in childhood.
53
Familial dysautonomia gene
ELP1 (aka IKBKAP)
54
Familial dysautonomia inher.
AR
55
Familial dysautonomia desc.
Affects autonomic (involuntary) system and sensory nervous system. Onset infancy. Hypotonia, poor growth, lack of tears, lung infections, temperature dysregulation, abnormal breathing patterns, blood pressure dysregulation, optic atrophy
56
Apo Alleles
"E4: risk conferring, but not necessary or sufficient for disease
E2: protective
E3: neutral"
57
Alzheimers (early-onset, AD) gene
APP, PSEN1, PSEN2
58
Frontotemporal dementia (AD) gene
MAPT and others
59
Frontotemporal dementia inher.
~50% sporadic
~30% familial
~20% AD
60
Frontotemporal dementia (AD) desc.
"Behavioral Variant (bvFTD)
Disinhibition, apathy, compulsive, diminished executive functioning
Primary Progressive Aphasia
Non-fluent type: motor speech problems
Semantic type: loss of word meaning
Behavioral changes, parkinsonism, eventually mute"
61
Lewy Body Dementia gene
SNCA, SNCB
62
Lewy Body Dementia inher.
AD
63
Lewy Body Dementia desc.
Dementia, parkinsonism, hallucinations, fluctuations in behavior and intellect, REM sleep disorder
64
CADASIL gene
NOTCH3
65
CADASIL inher.
AD
66
CADASIL desc.
"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Migraines, TIAs, psychiatric
Variable onset"
67
Waardenburg gene
PAX3, MITF, SOX10, SNAI2
68
Waardenburg inher.
ad
69
Waardenburg desc.
"Congenital SNHL (20-50% of pt), dystopia canthorum (pupils close set), heterochromia, blue eyes, white forelock, vitiligo, Hirschsprung disease
4 subtypes"
70
Usher gene
Type 1: MYO7A (~50%) and many others
71
Usher inher.
AR
72
Usher desc.
"Type 1: Congenital SNHL, vestibular dysfunction causes delayed milestones (walking, etc), adolescent onset RP
Type 2: Normal vestibular function
Type 3: Progressive/post lingual SNHL, late onset RP, variable vestibular function"
73
Jervell and Lange-Nielson syndrome gene
KCNQ1 and KCNE1
74
Jervell and Lange-Nielson syndrome inher.
AR
75
Jervell and Lange-Nielson syndrome desc.
Congenital SNHL, long QT, childhood fainting
76
Pendred gene
SLC26A4 (50%)
77
Pendred inher.
AR
78
Pendred desc.
Congenital SNHL, vestibular dysfunction, temporal bone abnormalities, goiter
79
BORS/ BOS gene
EYA1 and others
80
BORS/ BOS inher.
AD
81
BORS/ BOS desc.
Variable onset of conductive, SN, or mixed HL, branchial cysts, various renal anomalies, variable expressivity
82
Meckel Gruber syndrome gene
Many proposed. Ciliopathy
83
Meckel Gruber syndrome inher.
AR
84
Meckel Gruber syndrome desc.
Occipital encephalocele, cystic kidneys, postaxial polydactyly
85
Alport gene
COL4A3/COL4A4/COL4A5
86
Alport inher
2/3 x-linked, then AR and AD
87
Alport desc.
"Hallmark: microhematuria.
Renal prgression: hematuria, proteinuria, hypertension, renal insufficiency.
Progressive SNHL ~late childhood
Anterior lenticonus (pathognomonic, teens-20s in 15% of males), other eye anomalies
Female “carriers” can have renal disease
60% of males reach ESRD by 30y"
AD has later onset, no eye stuff
88
Autosomal Recessive Polycystic Kidney Disease gene
PKHD1
89
Autosomal Recessive Polycystic Kidney Disease desc.
Bilateral, microcysts
Liver involvement- cysts, hepatomegaly
If survive first year, 50% have ESRD by 10y
90
Autosomal Dominant Polycystic Kidney Disease gene
PKD1 (85%)
| PKD2 (15%)
91
Autosomal Dominant Polycystic Kidney Disease desc.
```
Adult onset (20s-30s), multisystem
Bilateral renal cysts, cysts in other organs (esp. liver), vascular anomalies (hypertension, aneurysm, etc)
```
92
FMR1-Related Disorders inher.
X-linked with maternal expansion. Anticipation
93
FMR1-Related Disorders molecular info
```
CGG repeat in 5’ UTR
Normal: 5-44
Intermediate: 45-54
Premutation: 55-200
Full: >200
```
94
FMR1-Related Disorders desc.
DD, ID, behavioral issues, autism, hypotonia, gastroesophageal reflux, strabismus, seizures, sleep disorders, joint laxity, pes planus, scoliosis, recurrent otitis media, mitral valve prolapse, aortic root dilatation, macroorchidism.
Premutation risk for FXTAS and FXPOI
95
Huntington Disease gene
HTT
96
Huntington Disease molecular info
```
"CAG repeat (polyglutamine disease)
Normal: <26
Intermediate: 27-35
Reduced Penetrance: 36-39
Full Penetrance: >40"
```
97
Huntington Disease inher.
AD with paternal expansion. Anticipation
98
Huntington Disease desc.
Coordination issues, chorea, depression, personality changes, delusions, speech difficulties, dysarthria, dysphagia
99
Spinal and Bulbar Muscular Atrophy gene
AR (androgen receptor)
100
Spinal and Bulbar Muscular Atrophy inher.
x-linked
101
Spinal and Bulbar Muscular Atrophy molecular info
```
"CAG repeat (polyglutamine disease)
More repeats = early onset and progression
< 34 = normal
> 38 = full penetrance
Repeat number fairly stable"
```
102
Spinal and Bulbar Muscular Atrophy desc.
"Feminization onset in adolescence (males)
Neuromuscular onset 30s-50s
Bulbar disease (fasciculations of the tongue, lips, or perioral region; dysarthria; dysphagia)
Spinal lower motor neuron disease
103
Myotonic dystrophy molecular info
```
"Type 1: CTG
Type 1: 150-1,000 repeats
Type 1 congenital: >1,000 repeats
Type 2: CCTG
Type 2: 75-11,000 repeats"
```
104
Friedreich's Ataxia molecular info
"GAA repeat in nuclear mt gene
Normal: 5-33
Fully penetrant: >66"
105
Congenital Adrenal Hyperplasia gene
CYP21A2 (~95%), CYP11B1 (~5%)
106
Congenital Adrenal Hyperplasia inher.
AR
107
Congenital Adrenal Hyperplasia desc. for CYP21A2:
```
For CYP21A2:
1) Classic
a) Salt-wasting (~75%)
Females with ambiguous genitalia
b) Simple virilizing
No salt loss
Females with ambiguous genitalia
2) Non-classic
Females with normal genitalia
```
108
Androgen Insensitivity Syndrome gene
AR
109
Androgen Insensitivity Syndrome inher.
X-linked
110
Androgen Insensitivity Syndrome desc.
CAIS- external female genitalia
| PAIS- spectrum of genital phenotype
111
Smith-Lemli-Opitz syndrome gene
DHCR7 (7-dehydrocholesterol reductase)
112
Smith-Lemli-Opitz syndrome inher.
AR
113
Smith-Lemli-Opitz syndrome desc.
Growth retardation, microcephaly, ID, cleft palate, cardiac defects, most have toe syndactyly, polydactyly, underdeveloped male genitalia
114
Cytochrome P450 oxidoreductase deficiency gene
POR
115
Cytochrome P450 oxidoreductase deficiency inher.
AR
116
Cytochrome P450 oxidoreductase deficiency desc.
Phenotypic range affecting reproductive organs and skeleton.
| Severe form also called Antley-Bixler Syndrome
117
Long QT gene
LQT1: KCNQ1
LQT2: KCNH2
LQT3: SCN5A
and others
118
Long QT inher.
Mostly AD
119
Long QT desc.
Onset often teens/20s,
LQT1: Exercise, emotion
LQT2: Noise, emotion
LQT3: Sleep
120
Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) gene
RYR2, CALM1 (AD)
| CASQ2, TRDN (AR)
121
Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) inher.
RYR2, CALM1 (AD)
| CASQ2, TRDN (AR)
122
Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) desc.
"Tachycardia triggered by stress (exercise, emotion)
| Typically childhood onset"
123
Brugada gene
Many, including SCN5A (~15-30%)
124
Brugada inher
AD
125
Brugada desc.
Na channelopathy
Ventricular arrhythmia, ST segment abnormalities. Brugada pattern can lead to an arrhythmia, which can lead to fibrillation, which can lead to syncope and/or arrest. Can induce pattern with exercise
126
Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) gene
Many, including PKP2 . Many are desmosomal genes (cell to cell adhesion and signalling)
127
Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) inher.
Most AD
128
Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) desc.
Replacement of myocardium with fibrofatty tissue
| Restrict exercise b/c accelerates replacement
129
Hypertrophic Cardiomyopathy (HCM) gene
MYH7, MYBPC3, others
130
Hypertrophic Cardiomyopathy (HCM) inher.
Most AD
131
Hypertrophic Cardiomyopathy (HCM) desc.
LVH with heritable component
| Most common cause of sudden cardiac death in young athletes
132
Dilated Cardiomyopathy (DCM) gene
TTN, LMNA, MYH6, MYH7, others
133
Dilated Cardiomyopathy (DCM) inher.
AD, AR, X-linked
134
Left Ventricular Noncompaction (LVNC) gene
MYH7 or MYBPC3 (~30%) or others
135
Left Ventricular Noncompaction (LVNC) inher.
Most AD
136
Left Ventricular Noncompaction (LVNC) desc.
Cardiac muscle in left ventricle is thick and appears spongy. Symptoms: palpitations, blood clots, arrhythmia, exercise intolerance, shortness of breath, fainting, lymphedema, SCD
137
Familial TAAD gene
ACTA2 (~15%)
138
Familial hypercholesterolemia gene
LDLR, APOB, PCSK9 and others
139
Familial hypercholesterolemia inher
Most AD
140
Familial hypercholesterolemia desc.
Cholesterol build up increases risk of heart disease. Xanthomas (cholesterol deposits) can occur around the eyelids and within tendons of the elbows, hands, knees, and feet. Homozygotes or compound heterozygotes have adolescent onset
141
OI gene
COL1A1 and COL1A2 (90%) and many others
142
OI inher.
AD for COL1A1 and COL1A2
143
OI molecular
Type I: Quantitative mutations
LoF variants. Often premature stop codons
Type II, III, IV: Qualitative mutations. Dominant negative. Typically substitution of a glycine
144
OI "type I"
Classic non-deforming OI with blue sclera (Type I): Mild, normalish stature, no DI, blue sclera, 50% hearing loss, wormian bones
145
OI "type II"
Perinatally lethal OI (Type II): Severe, very short stature, DI, dark blue sclera, small beaded ribs (pathognomonic), minimal calvarial mineralization, platyspondyly
146
OI "type III"
Progressively deforming OI (Type III): Severe, very short stature, DI, blue sclera, frequent hearing loss, thin bones, platyspondyly, wormian bones
147
OI "type IV"
Common variable OI with normal sclera (Type IV): Mild to moderate, variable stature, +/- DI, normal to grey sclera, variable hearing loss, +/- wormian bones
148
Loeys-Dietz gene
TGFBR1, TGFBR2, TGFB2, SMAD3
149
Loeys-Dietz inher.
AD
150
Loeys-Dietz desc.
Vasculature tortuosity, aneurysms, dissections (aortic and other), pectus excavatum or carinatum, scoliosis, joint laxity, arachnodactyly, talipes equinovarus, hypertelorism, bifid uvula, cleft palate, craniosynostosis, translucent skin, atrophic scars, easy bruising, uterine rupture, spontaneous pneumothorax, hernias
151
Stickler Syndrome gene and mech
COL2A1 (80-90%), COL11A1 (10-20%), and others
| COL2A1: premature stop resulting in haploinsufficiency
152
Stickler Syndrome inher.
AD (AR forms also exist)
153
Stickler Syndrome desc.
Ocular: myopia, cataract, retinal detachment
Hearing loss: conductive and sensorineural
Cleft palate (pierre robin), midface hypoplasia, mild spondyloepiphyseal dysplasia and/or precocious arthritis, MVP (but no aneurysm stuff). Think: eyes, ears, joints
154
Marfan Syndrome gene and mech
FBN1
25-35% de novo
dominant negative
155
Marfan Syndrome inher
AD
156
Marfan Syndrome desc.
Tall, thin, prominent brow, micrognathia, myopia, lens dislocation or abnormalities, stretch marks, hernia, aortic root dilation, mitral valve prolapse, pneumothorax, dural ectasia, long long bones, pectus deformities, scoliosis, pes planus, arachnodactyly, dental crowding, hypermobility
157
Ehlers Danlos Syndrome classic gene
Classic: COL5A1, COL5A2
158
Ehlers Danlos Syndrome classic inher
AD
159
Ehlers Danlos Syndrome classic desc.
Velvety, elastic skin, bruise easily, paper scarring, poor healing, joint dislocations and subluxations, chronic pain, pregnancy complications, decreased aortic stiffness
160
vascular eds gene
Vascular: COL3A1
161
vascular eds inher
AD
162
vascular eds desc.
Aneurysms; arterial, intestinal, uterine rupture; thin, translucent, inelastic skin
163
Van der Woude gene
IRF6
164
Van der Woude inher.
AD
165
Van der Woude desc.
Mixed clefting, lip pits
166
Witkop gene
MSX1
167
Witkop inher.
AD
168
Witkop desc.
Nail dysplasia, missing teeth
169
Kallmann gene
ANOS1
170
Kallmann inher.
X-linked (ANOS1)
AD (FGFR1 and others)
AR (others)
171
Kallmann desc.
Hypogonadotropic hypogonadism (delayed/absent puberty), impaired sense of smell, CL +/- CP, unilateral renal agenesis, hearing loss, dental anomalies
172
Ectrodactyly Ectodermal dysplasia gene
TP63
173
Ectrodactyly Ectodermal dysplasia inher
AD
174
Ectrodactyly Ectodermal dysplasia desc
CL +/- CP, cleft hands/feet, light hair, light eyes
175
CHARGE gene and mech
CHD7, Involved in chromatin remodeling.
176
CHARGE inher
Most de novo. AD
177
CHARGE desc
Coloboma, heart defects, choanal atresia, retarded growth, genitalia, ear anomalies, CL +/- CP
178
Treacher Collins gene
TCOF1
179
Treacher Collins inher
AD, 60% de novo
180
Treacher Collins desc
CP (~25%), hypoplasia of zygomatic and mandibular bones, ear abnormalities, hearing loss, vision problems, eyelid notch
181
Apert gene
FGFR2
182
Apert mech and inher
AD
GoF mutations
Advanced paternal age
Almost all de novo
183
Apert desc
Coronal (+/- other) craniosynostosis, hand differences (bone fusion, syndactyly), cleft palate (30%), bifid uvula, high broad forehead, mandibular prognathism, ~50% ID
184
Crouzon gene
FGFR2, FGFR3
185
Crouzon mech and inher
AD
| Advanced paternal age
186
Crouzon desc.
Craniosynostosis (any), frontal bossing, hydrocephalus, mandibular prognathism, normal intellect
187
Muenke gene
FGFR3
188
Muenke mech and inher
AD
GoF mutations
Advanced paternal age
de novo rate unknown
189
Muenke desc
Very variable. Various craniosynostoses, carpal-tarsal fusion diagnostic when present
190
Pheiffer gene
FGFR1, FGFR2
191
Pheiffer inher
AD, Advanced paternal age
192
Pheiffer desc
Coronal w or w/o sagittal, occasional clover leaf skull, hydrocephalus, broad thumb and broad big toe, range of ID
193
Saethre-Chotzen gene
TWIST
194
Saethre-Chotzen inher and mech
AD
Haploinsufficiency
de novo rate unknown
195
Saethre-Chotzen desc
Coronal, facial asymmetry
196
Cleidocranial dysplasia gene and mech
RUNX2, haploinsufficiency
197
Cleidocranial dysplasia inher
AD
198
Cleidocranial dysplasia desc
Delayed ossification of skull, open cranial sutures, wormian bones, hypoplastic clavicles, teeth differences
199
NF1 gene and mech
NF1
Haploinsufficiency of neurofibromin causes activation of Ras/MAPK pathway
NF1 is tumor suppressor gene
200
NF1 inher
"AD
50% de novo
Variable expressivity"
201
NF1 desc
CALMs; intertriginous freckling; neurofibromas and plexiform neurofibromas; iris Lisch nodules; osseous dysplasia; optic pathway glioma; nl neurocognitive function or mild impairment.
Pediatric cancers: optic pathway glioma, rhabdomyosarcoma, neuroblastoma, juvenile myelomonocytic leukemia
Adult cancers: malignant peripheral nerve sheath tumors, GIST, somatostatinomas, pheochromocytomas, breast cancer
202
Legius gene
SPRED1
203
Legius inher and mech
AD, LoF -> Dysregulated pathway
204
Legius desc
Like NF1, except no neoplastic features (neurofibromas, plexiform neurofibromas, iris Lisch nodules, and CNS tumors)
205
Noonan gene
PTPN11, KRAS, SOS
206
Noonan inher
"AD
Many de novo"
activation of pathway
207
Noonan desc
Craniofacial dysmorphic features; congenital heart defects; short stature; undescended testicles; ophthalmologic abnormalities; bleeding disorders; nl neurocognitive function or mild impairment; predisposition to cancer
208
Noonan with Multiple Lentigines gene
PTPN11, CRAF1/RAF1
209
Noonan with Multiple Lentigines inher
AD
210
Noonan with Multiple Lentigines desc
Same as Noonan syndrome, but with possible development of multiple skin lentigines as individuals age; unclear predisposition to cancer
211
Capillary Malformation–Arteriovenous Malformation Syndrome gene
RASA1
212
Capillary Malformation–Arteriovenous Malformation Syndrome inher and mech
"AD
30% de novo"
Hapolinsufficiency -> pathway activation
213
Capillary Malformation–Arteriovenous Malformation Syndrome desc.
Multifocal capillary malformations, which may be associated with arteriovenous malformations and fistulae
214
Costello gene
HRAS
215
Costello inher and mech
"AD
Almost all de novo"
activation of pathway
216
Costello desc
Coarse features; congenital heart defects; failure to thrive; short stature; ophthalmologic abnormalities; multiple skin manifestations, including papilloma; hypotonia; predisposition to cancer (rhabdomyosarcoma, neuroblastoma, transitional Cell carcinoma)
217
Cardio-Facio-Cutaneous Syndrome gene
BRAF, MEK1, MEK2, KRAS
218
Cardio-Facio-Cutaneous Syndrome inher and mech
"AD
Almost all de novo"
activation of pathway
219
Cardio-Facio-Cutaneous Syndrome desc
Congenital heart defects; failure to thrive; short stature; ophthalmologic abnormalities; ectodermal findings including sparse, curly hair with sparse eyebrows and eyelashes, hyperkeratosis, keratosis pilaris, hemangioma, ichthyosis, and progressively forming nevi
220
NF2 gene
NF2
221
NF2 inher and mech
```
"AD
50% de novo
Many pt's mosaic"
"Protein: merlin
Nonsense and frameshift often severe disease; missense often mild disease; deletions often mild disease
Part of Hippo pathway"
```
222
NF2 desc
"Avg onset: 20y
Bilateral vestibular schwannomas by 30y (sx: tinnitus, hearing loss, and balance dysfunction). Spinal tumors, meningioma, schwannoma, glioma (CNS), specific cataracts, retinal hamartomas
Feature in childhood: Mononeuropathy (frequently presents as a persistent facial palsy or hand/foot drop)
Avoid radiation tx. "
223
Schwannomatosis gene
SMARCB1, LZTR1
224
Schwannomatosis inher and mech
Most sporadic, but ~20% familial, tumor suppressor genes
225
Schwannomatosis desc
"Typically adult onset
| Schwannomas -> numbness, weakness, tingling, pain, headaches"
226
Hemochromatosis (Type 1) gene
HFE
227
Hemochromatosis (Type 1) inher and mech
AR
LoF
60%-90% of Euro ancestry cases homozygous for p.Cys282Tyr
Penetrance of biochemical pheno higher than penetrance of clinical pheno
1/10 euro ancestry carriers
228
Hemochromatosis (Type 1) desc
"Iron overload. Fatigue, joint pain, abdominal pain, arthritis, cirrhosis, liver cancer, diabetes, heart abnormalities, skin discoloration, shortage of sex hormones
Onset in men 40s-60s, in women after menopause
Tx: phlebotomy"
229
Hereditary Hemorrhagic Telangiectasia gene
ACVRL1, ENG, (SMAD4 but only 1-2%)
230
Hereditary Hemorrhagic Telangiectasia inher and mech
AD
All genes in TGF-β signaling pathway
De novo rare
231
Hereditary Hemorrhagic Telangiectasia desc
"Arteriovenous malformations (AVMs) lack intervening capillaries -> direct connections between arteries and veins.
Epistaxis (nosebleeds, onset ~12y), telangiectases (small AVMs) on mouth, face, chest, fingers, GI bleeding (onset >50y).
Large AVMs in lung (esp. pregnancy), liver, or brain (congenital) are serious"
232
Acute intermittent porphyria gene
HMBS
233
Acute intermittent porphyria inher and mech
AD
Penetrance <1%
LoF
Reduced activity of the enzyme porphobilinogen deaminase (in the heme biosynthetic pathway)
234
Acute intermittent porphyria desc
"Life-threatening acute neurovisceral attacks: severe abdominal pain, vomiting, tachycardia, hypertension, mental changes, convulsions, peripheral neuropathy that may progress to respiratory paralysis, and hyponatremia (low Na)
Increased risk of liver cancer, >50y"
235
Factor V Leiden gene
F5
236
Factor V Leiden mech
"c.1691G>A
Not susceptible to Protein C, so inactivated more slowly (leading to prolonged clotting)
~5% of Euro. ancestry are hets"
237
Factor V Leiden desc
Thrombophilia. VTE in ~1% (of pregnancies?) in women who are Leiden variant heterozygotes (gen pop background 0.1%). Risk up to ~10% in homozygotes. Esp during pregnancy
238
Prothrombin Thrombophilia gene
F2
239
Prothrombin Thrombophilia mech
"c.*97G>A, aka 20210G>A
| GoF mutation in the 3’UTR"
240
Prothrombin Thrombophilia desc
The risk for recurrent VTE in homozygotes is not well defined, but presumed to be higher than in heterozygotes
241
Hemophilia A gene
F8
242
Hemophilia A inher and mech
X-linked
"15% de novo
Genotype-phenotype correlation: males in same family similarly affected
Intron 22 inversions account for 45% of severe cases
Missense -> mild/moderate"
243
Hemophilia A desc
"Severity depends on amount of functional factor VIII.
| ~30% of heterozygous females have clotting activity below 40% and are at risk for bleeding"
244
Hemophilia B gene
F9
245
Hemophilia B inher and mech
X-linked
"Genotype-phenotype correlation: males in same family similarly affected
Missense often severe (unlike F8)"
246
Hemophilia B desc
"Severity depends on amount of functional factor IX.
~30% of heterozygous females have clotting activity below 40% and are at risk for bleeding.
Unlike factor VIII, maternal factor IX does not increase in pregnancy. More likely to need factor infusion during/after delivery. "
247
Von Willebrands gene
VWF
248
Von Willebrands inher and mech
"Types 1 and 2 mostly AD
Type 3 AR"
Quantitative or qualitative changes to Von Willebrand Factor
249
Von Willebrands desc
Mucocutaneous bleeding. Type 3 severe and can have musculoskeletal bleeding. Increased bleeding risk during/after birthing.
250
Alpha Thal gene
HBA1, HBA2 (mRNA identical except 3’UTR)
251
Alpha Thal mech
"Deletions most common variants
Non-deletion mutations tend to be more severe (eg HbH-constant spring)
beta trait can mask alpha trait"
252
Alpha Thal desc
"Alpha thal major / HbBart syndrome: no functioning alpha-globin genes. Typically stillbirth. Maternal risks.
Hemoglobin H disease: 1 functioning alpha-globin gene. Variable. Life-long mild to moderate anemia.
Alpha thal trait: 2 functioning alpha-globin genes. Healthy. Microcytosis. May be in cis (more Asian) or trans (more AA).
Silent carrier: 3 functioning alpha-globin genes. Healthy. MCV typically nl."
253
Beta Thal gene
HBB
254
Beta Thal mech and inher
AR
"No deletional mutations
beta trait can mask alpha trait"
255
Beta Thal desc
"Severity of beta thal syndromes depends on extent of imbalance between alpha and non-alpha chains being produced
Beta Thal Major- regular blood transfusions
Beta Thal Intermedia- transfusion rarely required
Beta Thal Minor- Carrier / Trait, HBA2 > 3.5%, MCV<80"
256
Hemoglobin C gene
HBB
257
Hemoglobin C desc
Structural variant
"Hemoglobin C Disease: homozygotes -> hemoglobin C. Mild to moderate anemia.
Hemoglobin C beta thal disease. Mild to moderate anemia
Hemoglobin SC disease- form of sickle cell disease"
258
Hemoglobin E gene
HBB
259
Hemoglobin E desc
"Hemoglobin EE: homozygotes -> hemoglobin E. Low MCV, healthy.
Hemoglobin E beta thal disease: Blood transfusions, life long care. Most common severe form of beta thalassemia world wide
High variability."
260
Sickle Cell Disease gene
HBB
261
Sickle Cell anemia variant
p.Glu6Val
| Hb S trait in 1/10 african americans
262
del(1)(p36)
Although the phenotype is variable, some of these patients have significant phenotypic overlap with Prader-Willi syndrome.
263
dup(1)(q21.1)
Variable. DD, ASD, ADHD, schizophrenia, ToF.
264
del(2)(q37.3)
Albright Hereditary Osteodystrophy.
265
inv(2)(p11.2q13)
A recurring pericentric inversion. There appears to be no increased risk for liveborn unbalanced recombinant offspring among these inversion carriers although the risk for spontaneous abortions and stillbirths appears to be increased approximately 2-fold
266
dup(3)(q26.3)
phenotypic overlap with Cornelia de Lange syndrome
267
del(4)(p16.3)
A classic chromosome deletion syndrome. Wolf-Hirschhorn syndrome. Phenotype includes severe growth and mental retardation, microcephaly, "Greek Warrior helmet" face, cleft lip and/or palate. Although the critical region for the syndrome is in 4p16.3, deletions can be large or small. A milder phenotype associated with similar deletions is seen in patients with Pitt-Rogers-Danks syndrome.
268
t(4;8)(p16;p23)
One of only 2 recurring constitutional reciprocal translocations; mediated by olfactory receptor gene clusters on chromosomes 4 and 8. Patients with unbalanced karyotypes and the der(4) have features associated with Wolf-Hirschhorn syndrome
269
del(5)(p15)
A classic chromosome deletion syndrome. Cri-du-chat syndrome named for the characteristic high pitched cry in infants with 5p deletions that include the p15.31 and/or distal p15.2 region. Phenotype includes microcephaly, severe motor and mental retardation, round face, hypertelorism, micrognathia.
270
del(5)(q35)
A classic chromosome deletion syndrome. The Sotos syndrome phenotype includes overgrowth, macrocephaly, mental retardation, hypotonia and poor coordination, advanced bone age and a typical facies (prominent forehead with recessed hairline, long narrow face, pointed chin, hypertelorism and large ears). Deletions are more common in the Japanese population (~ 50 of patients) than the non-Japanese (~10% of patients).
271
del(7)(q11.2q11.2)
Williams syndrome. A true contiguous gene syndrome. Phenotype includes supravalvular aortic stenosis (SVAS), "elfin" face, mental and growth retardation, infantile hypercalcemia. Patients with Williams syndrome often have remarkable musical and verbal abilities. This is a submicroscopic deletion detectable by FISH. Genes within the deleted region thought to contribute to the phenotype include elastin (SVAS, aortic shenosis); LIM Kinase 1 (cognitive impairment); RFC 2 gene (reduced efficiency of DNA replication - growth and developmental delay).
272
del(7)(q36)
Several patients have been reported with distal deletions in 7q and holoprosencephaly (type 3). 7q36 is the location of the sonic hedgehog gene.
273
del(8)(q24.11-24.13)
Associated with the Langer-Giedion syndrome. This is probably a true contiguous syndrome with symptoms caused by disturbances of both the TRPS1 gene and EXT1. Phenotype includes mental retardation, microcephaly, multiple exostoses (growth on bone), redundant skin, and sparse hair.
274
inv(8)(p23.1q22.1)
This pericentric inversion is typically seen in individuals of Hispanic descent with ancestry from the San Luis Valley of southern Colorado and northern New Mexico. These inversion carriers have an ~6% chance of having a child with recombinant 8 syndrome. The recombinant chromosome 8 contains a duplication of q arm material (q22.1qter) and a deletion of p arm material (p23.1pter). Children with this recombinant chromosome typically have MR, heart defects, seizures and a characteristic facies (hypertelorism, thin upper lip, anteverted nares, wide face, abnormal hair whorl, low set ears, downturned mouth, low posterior hairline, etc).
275
Trisomy 8.
Although full trisomy 8 is often lethal, many patients have been reported with mosaic trisomy 8. The phenotype includes a variable degree of MR (mild to moderate) with a tendency to poor coordination, prominent forehead, deep set eyes, strabismus, hypertelorism, cleft palate, joint contructures and other skeletal abnormalities, deep creases on palms and soles.
276
t(8;14)(q24;q32)
present in 75-85% of Burkitt's lymphoma cases
277
del(9)(p24)
Partial monosomy 9p is associated with male to female sex reversal suggesting the presence of a gene important for normal male development. Patients with 9p deletions also have MR, motor development delay, trigonocephaly, wide nasal bridge, long fingers and toes, etc.
278
inv(9)(p11q13)
A recurring pericentric inversion that is not associated with an increased risk for liveborn unbalanced recombinant offspring, spontaneous abortions or stillbirths.
279
Trisomy 9 mosaicism.
Phenotype includes severe MR, and growth deficiency, sloping forehead, deeply set eyes, joint contractures, and heart defects.
280
t(9;22)(q34.1;q11.2)
Philadelphia chromosome. 90% of patients with chronic myeloid leukemia (CML) have the Philadelphia chromosome
281
del(10)(p13-14)
A small number of patients with the DiGeorge phenotype have been reported with deletions of 10p.
282
dup(11)(p15.5)
Patients with duplications in this region of 11p have been reported with Beckwith-Wiedemann syndrome. The primary features associated with this syndrome include macroglossia (enlarged tongue), omphalocele (protrusion of abdominal contents through umbilicus, macrosomia (gigantism) and ear creases.
283
del(11)(p13)
Interstitial deletions of 11p13 are associated with WAGR (Wilms tumor; aniridia-genitourinary anomalies-mental retardation syndrome). This is a true contiguous gene syndrome with separate genes responsible for aniridia (AN2) and Wilms tumor and genitourinary anomalies (WTI).
284
del(11)(p11.2)
Potocki-Shaffer syndrome is a newly recognized deletion syndrome. These patients typically have multiple exostoses, an enlarged parietal foramina, craniofacial dysostosis and MR.
285
del(11)(q23)
Deletions including 11q23 are associated with Jacobson syndrome. Phenotype includes growth and psychomotor delay, trigonocephaly, strabismus, telecanthus, camptodactyly, thrombocytopenia. This deletion may be caused by an inherited fragile site at 11q23.3 in some patients.
286
"plus"i(12)(p10)
Tetrasomy 12p secondary to an extra isochromosome of 12 short arm is associated with Pallister-Killian syndrome. This syndrome is an example of tissue limited mosaicism. The isochromosome 12p is typically found in fibroblasts, but not in the lymphocytes. Phenotype includes profound MR, seizures, streaky pigmentation, sparse hair (especially in temporal areas), coarse facial features in older patients.
287
del(13)(q14.2)
Deletions of 13q that overlap this region are associated with a high risk of developing retinoblastoma (tumor of the retina).
288
del(15)(q11-13)pat
Prader Willi
Paternal deletion: ~75%
mat UPD: 25%
Paternal imprinting defect: ~1%
Lack activity of paternal genes MKRN3, MAGEL2, NDN, SNURF-SNRPN, and several snoRNA genes (as well as overexpression of maternal genes UBE3A and ATP10C) in 15q11q13
UPD usually nondisjunction in maternal meiosis I (associated with AMA)
Hypotonia, failure to thrive, DD/ID, obesity, short stature, hypogonadism, behavior problems, small hands and feet, hypopigmentation.
289
del(15)(q11-13)mat
Angelman
Maternal deletions : 65-75%
Maternal UBE3A mutations: 5-11%
Paternal UPD: 3-7%
Maternal imprinting defects: 3%
Unknown: 15-20%
Lack the activity of the maternally expressed UBE3A (and ATP10C) genes in 15q11q13
Imprinted UBE3A expression restricted to brain cells (normal).
Typically isodisomic (postzygotic monosomy rescue, associated with null ovum and AMA) or more rarely paternal meiosis II errors
ID, absent speech, ataxia, hypertonia after infancy, microcephaly, seizures, happy/laughing disposition
290
"plus" inv dup(15) or psu idic(15)(q)
These small, often dicentric chromosomes are composed of 2 copies of chromosome 15 short arm, (usually) 2 centromeres and 2 copies of varying amounts of proximal 15q material. If the "marker" contains the probe loci that are usually deleted in PWS/AS, the patient will have MR and often autism. If these loci are not present in the marker, the phenotype can be normal. These are the most common identifiable markers or ESAC's seen in the human population.
291
t(15;17)(q22;q11-21)
Acute Promyelocytic leukemia (APL) (form of AML). Pathognomonic
292
del(16)(p13.3)
alpha-thalassemia/MR syndrome. Patients with small deletions in 16p have been observed with alpha thalassemia, MR, and a broad spectrum of associated anomalies.
293
del(16)(p13.3)
Rubinstein-Taybi syndrome can also be associated with deletions in this region. Phenotype includes broad thumbs and great toes, mental retardation, small mouth, beaked nose, micrognathia, low hair line, heart defects, skeletal abnormalities.
294
dup(16)(p11.2)
Microcephaly, DD, ID, ADHD
295
del(17)(p13.3)
Miller-Dieker syndrome; 90% of patients with MDS have either a visible or submicroscopic deletion in this region. Phenotype: microcephaly, with lissencephaly (smooth brain). Also unusual facial appearance, and malformations of the heart and kidneys, polydactyly.
296
del(17)(p11.2)
Visible deletions in this region are associated with Smith-Magenis syndrome. Phenotype includes brachycephaly, midface hypoplasia, prognathism, hoarse voice, MR, growth retardation, behavior problems (including self-destructive behavior and sleep disturbances). More distally placed deletions within the 17p11.2 band are associated with HNPP.
297
dup(17)(p11.2)
Several patients have now been reported with visible duplication of the same region deleted in Smith-Magenis syndrome. These patients had developmental delay without distinctive physical features.
298
del(17)(p11.2)
(Generally submicroscopic) Deletion of the same region duplicated in CMTIA is associated with Hereditary Neuropathy with liability to Pressure Palsies (HNPP). More proximally placed deletions involving the 17p11.2 band are associated with Smith Magenis syndrome
299
dup(17)(p11.2)
(Generally submicroscopic) duplications of this region are associated with Charcot-Marie Tooth disease (CMTIA), a peripheral neuropathy associated with muscle weakness. Deletions of this region are associated with HNPP
300
18p deletion
Deletion of all or a large portion of 18p is a classic chromosome deletion syndrome. The associated phenotype includes moderate growth deficiency, MR, hypotonia, microcephaly, holoprosencephaly, micrognathia, large ears.
301
18q deletion
classic chromosome deletion syndrome. These are relatively large deletions, some interstitial, some apparently terminal. The phenotype includes MR, short stature, hypotonia, hearing impairment and foot deformities.
302
del(20)(p12.3)
del(20)(p12.3) Deletions in this region are associated with Alagille syndrome, although fewer than 7% of individuals with Alagille have visible deletions. Alagille syndrome is caused by mutations of JAG1. Phenotype includes paucity of intrahepatic bile ducts, posterior embryotoxin (visible ring in the cornea) and other anomalies.
303
del(22)(q11.2)
This small deletion in proximal 22 is associated with DiGeorge/VCF (velocardiofacial AKA Shprintzen syndrome. DiGeorge syndrome is the infantile presentation including neonatal hypocalcemia, susceptibility to infection, and conotruncal heart anomalies. In older children, VCF syndrome includes bulbous nose with square nasal tip, hypernasal speech with (generally) milder cardiac anomalies. Short stature and mild-to-moderate learning disabilities are often seen, as well as psychiatric disorders in adults. The acronym CATCH 22 [cardiac abnormality, abnormal facies, T-cell deficit due to thymic hypoplasia, cleft palate, hypocalcemia, resulting from del(22)(q11)] has been proposed to describe the variable phenotype. Although the majority are de novo, approximately 10% are inherited deletions from an affected (often mildly affected) parent.
304
"plus"idic(22)(q11.2)
Cat eye syndrome. An extra small marker chromosome is present representing tetrasomy (or occasionally trisomy) of 22q11.2. Phenotype includes mild mental retardation, coloboma of the iris, downslanting palpebral fissures, preauricular tags or pits, and anal atresia.
305
del (22)(q13)
Phelan-McDermid syndrome. Infantile hypotonia, normal growth, profound developmental delay, absent or delayed speech, and dysmorphic features. Decreased pain sensitivity. Decreased sweating. Cyclic vomiting.
306
del(X)(p22.3p22.3)
Males have X-linked ichthyosis.
307
del(X)(p22.3p22.3)
Males with Kallmann syndrome typically carry a submicroscopic deletion involving the Kallmann syndrome 1 (KAL1) gene and demonstrate hypogonadotropic hypogonadism and anosmia (inability to smell). Carrier females typically have milder manifestations.
308
dup(X)(p22p22)
PLP PROTEOLIPID PROTEIN 1; Pelizaeus-Merzbacher disease is a dismyelinating disorder of the CNS; clinical signs include nystagmus, spastic quadriplegia, ataxia and developmental delay.
309
dup(X)(p21p21)
Sex-reversed XY males result from duplication of the DAX1 gene. In the presence of a DAX1 duplication, the male determining function of SRY is suppressed and ovarian development results.
310
inv(Y)(p11;q11)
This pericentric inversion typically represents a benign variant, however some inversions have been reported in males with infertility due to a small accompanying deletion.
311
UPD 6 pat
```
Transient neonatal diabetes mellitus
~33% of cases
"~33% maternal hypomethylation
~33% paternal duplication
Overexpression of the imprinted loci PLAGL1 and HYMAI in 6q. Macroglossia, other congenital anomalies
```
312
UPD 7 mat
Russell-Silver syndrome
~7-10% of cases
Loss of paternal methylation at IC1: 35-50%
Unknown: 40%
Maternal duplication of IC1 and IC2: 1-2%
Hypermethylation of the imprinting center of the MEST gene in 7q
Prenatal and postnatal poor growth, relative macrocephaly, hemihypoplasia
313
UPD 11 mat
```
Russell-Silver syndrome
Rare, <10 known cases
Hypomethylation of IC1 in 11p
Biallelic expression of H19
Silencing of IGF2
Postzygotic origin
```
314
UPD 11 pat
Beckwith–Wiedemann syndrome
~20% of cases
Loss of maternal methylation at IC2: 50%
Unknown: 20%
Gain of maternal methylation at IC1: 5%
Maternal CDKN1C mutations: 5%
Other chrm. abnormalities: 1%
Abnormalities within two differentially methylated regions 11p: imprinting center 1 (IC1), which regulates the expression of H19 and IGF2, and imprinting center 2 (IC2), which regulates the expression of CDKN1C, KCNQ1, and KCNQ10T1.
Arises from postzygotic somatic recombination (hypothesis that whole UPD11 is lethal)
IGF2 is a fetal growth factor (biallelic expression responsible for overgrowth)
Congenital overgrowth, predisposition to tumorigenesis, hemihyperplasia
315
UPD 14 mat
Temple syndrome
Loss of expression of all paternally expressed genes (DLK1, RTL1, and DIO3) and overexpression of maternally expressed genes (noncoding
RNAs, miRNAs, and snoRNAs) at 14q
Most common cause of TS
Prenatal and postnatal poor growth, mild DD, hypotonia, hypermobility, small hands and feet, truncal obesity, precocious puberty, short stature
316
UPD 14 pat
Kagami–Ogata syndrome
Severe phenotype with polyhydramnios, large omphalocele, thoracic dysplasia (coat-hanger sign on X-rays = pathognomonic), with respiratory failure, abdominal wall defects, poor growth, developmental delay, and facial abnormalities
317
McCune-Albright syndrome
Not inherited. Sporadic and mosaic throughout body (GNAS mutation)
polyostotic fibrous dysplasia, precocious female puberty, coast of Maine skin findings, various endocrine problems
318
Achondrogenesis inher
"Type 1: AR
| Type 2: AD; ~100% de novo"
319
Achondrogenesis desc
"Severe. Small body, short limbs, other skeletal anomalies.
| Often stillborn or die in infancy"
320
Chromosome instability syndromes
Fanconi, AT, Bloom
321
Microarray is first tier test for
ID, DD, autism, and multiple congenital anomalies
322
~X% of pt with normal CMA and abnormal phenotype have a balanced rearrangement on karyotype
1%
323
When is karyotype warranted after microarray?
Karyotype for complex rearrangements indicated when multiple CNVs identified on array
324
Ethics of recontacting
Attempt to recontact if new info that could impact care is available (based on beneficence)
Discuss recontact plan at initial results
Shared responsibility of lab, provider, and pt
325
Imprinting chromosomes
6, 7, 11, 14, 15, 20, (x)
326
Nondisjunction in meiosis I can result in (upd)
heterodisomy
327
Nondisjunction in meiosis II can result in (upd)
isodisomy
328
How do you distinguish between UPD vs abnormal methylation?
Satellite marker analysis
329
1/x live births has a chromosomal abnormality
150
330
With low fetal fraction (drawn at appropriate date) offer
diagnostic testing, not repeat NIPS
331
Criteria for conditions that should be included in gen pop carrier screening
Most at risk couples would consider prenatal dx for this condition
332
All planning or pregnant women should be offered screening for
SMA, CF, and a CBC for anemia and hemoglobinopathies
333
genome editing statement
Embryos should not have gene editing at this time
334
Pathogenic variants in X genes should be reported as X findings if encountered on WES/WGS
59, secondary
335
Active engagement in WES/WGS consent starting around age X, depending on maturity of child
8
336
CHD 22q
ToF>IAA and VSD
337
CHD CHARGE
Conotruncal defects
| AV canal defects, aortic arch anomalies
338
CHD Alagille
Pulmonary artery stenosis, VSD, ToF
339
CHD Noonan
Pulmonic stenosis, HCM
340
CHD Williams
Supravalvar aortic stenosis
| pulmonic stenosis, coarctation of aorta
341
CHD Turner
Coarctation of the aorta
| bicuspid aortic valve, ASD, VSD, hypoplastic left heart, regurgitation, aortic aneurysm and dissection
342
CHD with Increased Pulmonary Flow
VSD, ASD, AVSD, PDA
343
CHD with Cyanosis / Left to Right Shunt
Transposition of Great Arteries, Persistent Truncus Arteriosus, Tetralogy of Fallot, Tricuspid Atresia, Pulmonary Atresia, Ebstein Anomaly
344
Pulmonary stenosis
Pulmonary valve is too small, narrow, or stiff
345
Persistent Truncus Arteriosus
Single blood vessel (truncus arteriosus) comes out of the right and left ventricles, instead of the normal 2 vessels (pulmonary artery and aorta)
346
Tetralogy of Fallot
VSD, overriding aorta (aorta shifted to above VSD, so gets blood from both ventricles), pulmonary stenosis, right ventricular hypertrophy
347
Ebstein Anomaly
Tricuspid valve (between right ventricle and atrium) malformed
348
Most common cause of BWS
Loss of maternal methylation at IC2 (50%)
349
Thrombophilias
Factor V Leiden, prothrombin thrombophilia, protein s deficiency, protein c deficiency
350
estrogen containing birth control contraindicated for
Factor V Leiden homozygotes (or hets with VTE Hx)
351
HbF
2 alpha, 2 gamma
352
HbA2
2 alpha, 2 delta
353
HbH
beta tetramer
354
HbBarts
gamma tetramer
355
MCV with hemoglobin Bart hydrops
high!
356
Hb Constant Spring
Nucleotide change in stop codon of HBA2, resulting in 31 extra aa
357
SMN2
Pseudogene of SMN1. Has single nucleotide difference that causes 85% of transcripts to skip exon 7, making that 85% nonfunctional
358
Type 4 CMT inher
AR (1 and 2 are AD)
359
LGMD Type 1
AD
360
LGMD Type 2
AR
361
Autism spectrum frequency
1/60 children
362
cma yield for asd
5-15% yield
363
Recurrence risk for idiopathic ASD in a sibling
up to 20% (ACMG has 4-7%)
364
No invasive procedures (eg c'spy) for this condition
Vascular EDS
365
Cleft Lip +/- cleft palate: between X-X% will have additional “problems” (additional defects, chromosome abnormalities)
7-35%
366
Cleft palate only: X% isolated
50%
367
NTD/AWD serum screening
AFP > 2.5 Mom
