Genetics Flashcards

1
Q

Malformation

A

Abnormal tissue formation (e.g. renal agenesis, micrognathia, cleft palate, CHD)

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2
Q

Deformation

A

Associated with altered mechanical forces (extrinsic or intrinsic) on normal tissue (e.g. arthrogryposis from in utero constraints)

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3
Q

Disruption

A

Breakdown of normal tissue; destructive (e.g. amniotic bands, porencephaly, limb reduction from vascular anomalies)

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4
Q

Dysplasia

A

Abnormal organization of cellular formation into tissue; deregulation (e.g. hemangioma, ectodermal dysplasia)

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5
Q

Syndrome

A

Pattern of many primary malformations due to one etiology d/t ch abn, single gene d/o, or teratogen

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6
Q

Sequence

A

Primary defect with secondary effects (e.g. pierre robin sequence 2• to primary mandibular maldevelopment with secondary findings of micrognathia, cleft palate, and glossoptosis)

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7
Q

Mitochondria do

A

Can present at any age
S/s: lethargy, hypotonia, FTT, seizures, cardiomyopathy, hearing or visual deficits, movement do

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8
Q

Recurrence risk cardiac defect
1 previous child
2 previous children

A

1 previous -> 3-4% risk to next child
2 previous -> 10% risk to next child

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9
Q

Recurrence risk of cleft lip
1 previous child with unaffected parents
1 previous child with 1 affected parent

A

1 child & unaffected -> 4-5%
1 child & 1 affected -> 10%

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10
Q

Recurrence risk of cleft palate
1 previous child

A

1 previous -> 2-6%

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11
Q

Recurrence risk of club foot
1 previous child
1 previous child and 1 affected parent

A

1 previous -> 2-5%
1 previous and 1 parent -> 25%

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12
Q

Recurrence risk of Hirschsprungs
1 previous

A

1 previous child -> 3-5%

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13
Q

Recurrence risk of NTD
1 previous child

A

1 previous -> 3-5%

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14
Q

Recurrence risk of pyloric stenosis
Father
Mother
1 previous child

A

Father -> 5.5% son 2.4% daughter
Mother -> 19% son 7% daughter
1 previous child -> 3%

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15
Q

Recurrence risk of T21
Mother balanced translocation
Father balanced translocation
1 previous child & no translocation

A

Mother balanced translocation -> 10-15%
Father balanced translocation -> 5%
1 previous child & no translocation -> 1% unless AMA

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16
Q

Allele frequency calculations

A

p + q = 1 for allele frequency and then x100 for percent
p^2 + 2pq + q^2 = 1 where p^2 is AA, 2pq is Aa and q^2 is aa
For calculating prevalence, recessive and dominance, etc

Page 92 & 93 for examples

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17
Q

T13
Features

A

Patau syndrome
Midline abnormalities
Cardiac (vsd > pda)
Cutis aplasia
Narrow hyperconvex fingernails
Cleft lip, palate, small eyes
Holoprosencephaly
Persistent fetal Hb
Increased PMN with nuclear projections

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18
Q

T18
Clinical features
Triple screen

A

Edwards syndrome
Cardiac (vsd, pda > bicuspid Av, PS, CoA, TOF)
Clenched hands with overlapping
Small mouth
Short sternum
Triple screen: low bHCG, low unconj estradiol, low afp

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19
Q

T21
Clinical features
triple screen

A

94% complete trisomy
3-5% robertsonian translocation
2% mosaicism
Cardiac (endocardial cushion defect > vsd > pda > anomalous subclavian artery, mvp, AR)
Hyperflexibility of joints
Upslanting palpebeal fissures, flat nasal bridge, brushfield spots (speckled iris), short neck
Hypotonia
Tmd (can present in utero with hydrops)
Leukemia (15-20x compared to general population)

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20
Q

T21 postnatal eval

A

Echo
Red reflex (r/f catarct)
Mbss if issues feeding
Hearing screen
Carseat test if hypotonia
Cbc for tmd
Tsh

First year: referal to sleep medicine if c/f OSA, peds ophtho, repeat tsh at 6 & 12 mo then annual, hb at 1year

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21
Q

Cri du chat syndrome

A

Deletion 5p
Deleted portion is of paternal origin in 80%
CV: VSD, PDA, TOF
Facial: hypetelorism, downward slant palpebral fissures
Neuro: cat like cry, IQ, microcephaly, hypotonia
FTT

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22
Q

Deletion 13q syndrome

A

Thumb hypoplasia, colobomas, ^risk of retinoblastoma, microcephaly, high nasal bridge

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23
Q

Wolf Hirschhorn syndrome

A

Deletion 4p
High forehead, broad or beaked nose, hyperteleorism, low set simple ear with preauricular dimple, microcephaly, cranial asymmetry

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24
Q

Angelman syndrome

A

70% d/t 15q11-13 deletion - deleted maternal origin
20-30% d/t point mutation or other abn of maternal 15q11-13 region
Puppet like gait, elfine, seizures

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25
22q11.2 microdeletion
Majority de novo CATCH 22 - cardiac, abn facies, thymic hypoplasia, cleft palate, hypocalcemia AD Aortic arch abn, vsd, pda, tof Deficient cellular immunity
26
Prader willi Syndrome
75% deletion of paternal origin 15q11-13 Small hands and feet, undescended testes, hypotonia Test - methylation analysis Ch analysis to assess recurrence risk Can do FISH
27
Rubenstein Taybi syndrome
Majority sporadic 16p13.3 Cardiac, broad thumbs, broad first toe, downward palpebral fissures, hypoplastic maxilla, narrow palate, prominent or beaked nose, microcephaly
28
WAGR syndrome
11p13 microdeletion Wilms tumor, aniridia, gu abn, IQ
29
Williams syndrome
7q11.23 deletion leads to deletion of elastin gene Supravalvar subaortic stenosis > pps Hypoplastic nails, prominent lips, stellate iris, IQ
30
Apert syndrome
Acrocephalosyndactyly AD Majority sporadic Mut FGFR 2 Hypertelorism, midface hypoplasia, broad thumb and big toe, syndactyly, craniosynostosis
31
Crouzon syndrome
Craniofacial dystosis AD mut FGFR 2 Hypertelorism, maxillary hypoplasia, craniosynostosis, shallow orbits
32
Holt Oram syndrome
AD with variable expression Cardiac: ASD, VSD, CoA, conduction defect Upper limb defects, absent hypoplastic or abn shaped thumbs, narrow shoulders
33
Marfan syndrome
Abn fibrillin gene on 15q21.1
34
Noonan
Abn mapping of 12q22 region Sporadic but can be AD Dysplastic pulm valve, asd, cardiomyopathy Pectus excavatum Webbed neck Abn coagulation pathway
35
Ddx for noonan
45 X/XY mosaic Fetal hydantoin exposure Fetal alcohol syndrome
36
Stickler syndrome
AD variable expression Mut type II collagen on 12q13 Hereditary arthri-ophthalmopathy Flat facies Can be a/c pierre robin Cataracts, retinal detachment, myopia, spondyliepiphyseal dysplasia (flat vertebrae with anterior wedging, poorly developed distal tibial epiphyses, flat femoral epiphyses)
37
Treacher collins syndrome
AD, variable expression Manibulofacial dysostosis May result from mut in TCOF1 gene (ch 5) => 1st and 2nd branchial arch maldevo Lower eyelid coloboma, mandibular hypoplasia, dysmorphic ears, malar hypoplasia Conductive hearing loss
38
Ellis-van Creveld syndrome
AR Chondroectodermal dysplasia Single atrium or ASD short distal extremities, polydactyly Narrow thorax 50% mortality in infancy d/t cardioresp difficulties
39
Fanconi pancytopenia syndrome
AR ^# of ch breaks in lymphocytes ans AF cells Hyperpigmentation, radial and thumb hypoplasia, short stature Pancytopenia (typically presents in childhood) 35% mortality and have ^ risk of AML
40
Meckel Gruber syndrome
AR Cardiac defect, polydactyly, occipital encephalocele, cystic dysplastic kidneys Range of phenotypic variability
41
Smith Lemli Opitz syndrome
AR Defect in cholesterol synthesis 2nd and 3rd toe syndactyly, anteverted nostrils, cataracts, hypogenitalia, hypotonic in infancy to hypertonic Prenatal diagnosis is possible (dec AF cholesterol)
42
Thrombocytopenia radial aplasia syndrome
AR Low plt, eosinophilia, granulocytosis, anemia Absent blt radii and ulnar abn 40% mortality because of hemorrhage early in infancy
43
Fryns syndrome
AR CDH, ^risk of hirschsprung, duodenal atresia, imperforate anus Dandy walker malformation, IQ low Cloudy cornea, coarse facial features Digital and nail hypoplasia
44
Menkes syndrome
X linked recessive Kinky hair syndrome Abn of copper transport leading to copper deficiency Copper is a cofactor for many enzymes Progressive cerebral deterioration, hypertonia, seizures Majority death in early infancy
45
Charge syndrome and work up
Ch8q12 mut in CHD7 which alters chromatin AD but majority de novo Eval: echo, ophtho, otolaryngology, RBUS, hearing screen, CT temporal bones, karyotype Need 4 mj or 3 mj & 3 minor
46
Cat eye syndrome
Extra part of ch 22 usually at 22q11 position Cardiac, anal atresia, coloboma of iris
47
Cornelia de lange syndrome
Mut in 1 of 3 cohesin-associated genes Vsd>tof Micromelia, synophyrs, thin down turning upper lip, initial hypertonicity
48
Golderhar syndrome
Oculo-auriculo-vertebral spectrum or facio-auriculo-vertebral spectrum Unknown etiology 1st and 2nd brachial arch abnormalities Vsd>pda>tof>coa Microtia, malar maxillary or mandibular hypoplasia, ear tags or pits, microphthalmia Deafness with normal intelligence Unilateral renal anomalies
49
Klippel Feil sequence
Unknown etiology Early developmental defect of cervical vertebrae Short neck, low hairline, limited rom of head, deafness Can be a/c sprengel deformity (failure of scapula to descend)
50
Klippel Trenaunay Weber syndrome
Unknown etiology Asymmetric limb hypertrophy Vascular lesions
51
Poland sequence
Unknown etiology Unilateral hypoplasia or absence of pectoralis muscle
52
Russel silver syndrome
Small triangular facies, micrognathia, short stature, congenital asymmetry of skeleton, 5th finger clinodactyly
53
VACTERL association
Increased risk in IDM Can have VACTERL with H for hydrocephalus Can have fanconi anemia Dx of exclusion 3 major required Those who meet criteria, 1/2 will have genetic abnormality and 1/2 will have isolates VACTERL
54
Evaluation for VACTERL
CXR, echo, RBUS, xray spine, spinal US, HUS, radiograph of extremities if visual abn, ophtho exam Cbc (for overlapping abn) Chromosomal analysis - microarray to exclude other causes Ch breakage assay to assess for fanconi anemia
55
Trisomy 21 evaluation
Newborn: echo, red reflex, consider MBSS, cbc (for tmd), brainstem auditory evoked response or otoacoustic emission, ATT if hypotonic, TSH if NBS only tests fT4 First year: CBC annually starting at age 1, TSH at 6 and 12 months, sleep study if osa, cervical spine neutral position for procedures, ophthalmology eval by 6 months
56
Cri du chat syndrome
5p deletion syndrome (usually deleted portion is parental) Hypertelorism, down slanting palpebral fissures, round face, epicanthal folds, strabismus, low ears Mental deficiency, cat like cry (abn laryngeal development), microcephaly, hypotonia 30% have VSD, PDA, TOF
57
Deletion 13 q syndrome
Colobomas, risk retinoblastoma, hypertelorism, ptosis, high basal bridge, low set and malformed ears, micrognathia, microcephaly Thumb hypoplasia, 5th finger clinodactyly, short big toe Hypospadius, cryptorchidism IUGR, mental deficiency
58
Deletion 4p syndrome (wolf hirschhorn syndrome)
Most de novo High forehead, broad or beaked nose, hypertelorism, low set simple eat with preauricular simple, prominent glabella Microcephaly, cranial asymmetry, hypotonia, seizures, cardiac abnormalities
59
Arachnodactyly a/c
Homocystinuria and Marian syndrome
60
Camptodactyly a/c
Trisomy 8 Isolated
61
Cleft lip &/or palate a/c
CHARGE association, DiGeorge, meckel gruber, Pierre Robin, smith Lemli opitz, trisomy 13, goldenhar, treacher collins
62
Clinidactyly a/c
Carpenter syndrome, Cornelia de Lange syndrome, deletion 13q, klinefelter, rubenstein taybi, t21, holt oram, prader willi
63
Coloboma a/c
Cat eye syndrome, charge, deletion 13q, treacher collins, t13
64
Cystic hygroma a/c
Noonan, Turner, t13,28,21
65
Ocular hypertelorism a/c
Apert, cat eye, cri du chat, crouzon, deletion 13q, DiGeorge, Noonan, t8, Turner
66
Hypotelorism a/c
Holoprosencephaly Meckel gruber, Williams, t13
67
Limb hypertrophy a/c
Beckwith wiedemann and klippel trenauney Weber syndrome
68
Lip thick or prominent a/c
T8, WAGR, Williams
69
Hypogenitalia a/c
Carpenter, klinefelter, prader willi, SLO
70
Macroglossia is a/c
BWS, congenital hypothyroidism, t21
71
Micrognathia a/c
Cat eye, charge, Cornelia de Lange, deletion 13q, DiGeorge, marfan, Meckel gruber, mobius, Pierre Robin, russel silver, SLO, t8, t18, WAGR
72
Radial hypoplasia a/c
Fanconi, TAR, vacterl, Cornelia de Lange, holt oram, Poland, t13, t18
73
Syndactyly a/c
Apert, carpenter, CdL, isolated, Poland, SLO, t21, vacterl