Cytogenetic Disorders Flashcards
Triploidy
Microsomia, 3-4 syndactyly, large cystic placenta
Dispermy, polar body retention, meiotic nondisjunction could have occurred. Die early in newborn period.
Down’s syndrome etiology and risk
Mostly maternal non-disjunction leading to trisomy 21. Also could be mosaic or unbalanced translocation (3% each).
risk at 35 yo: 1/370 (4x at 20 yo, 1/2-2/3 of total risk)
risk at 20 yo: 1/1660
Most common Down signs
Short, mental retardation, upslanting palpebral fissures, increased skin on back of neck, hearing loss (all 80% or more)
How is Down typically fatal?
(infant) Heart, leukemia, respiratory
(adult) immune, aging, dementia
What evaluations are typical in Down?
EKG, Thyroid screen, Hearing/vision screen, C-spine radiograph
What are findings of both trisomy 13 and trisomy 18?
Rocker bottom feet, heart issue, mental retardation, poor survival
What are findings of trisomy 18?
Small, postmature, micrognathia, weird occiput/forehead/ears, digit overlap, omphacele
What are findings of trisomy 13?
cleft lip, polydactyly, scalp, holoprosencephaly
Turner syndrome…why are they abnormal?
short, delayed puberty, ovary problems, webbed neck, big ears, downslanting palpebral fissures, kidney and heart problems
Abnormal because some genes on silenced X escape inactivation and are necessary for normal development. Both X’s active in oogenesis, embryogenesis.
Klinefelter
normal till puberty. hypogonadism, infertility due to azospermia. tall, gynecomastia
Cri du Chat
shrill cry, 5p deletion, microcephaly, round face, hypotonia
Wolf Hirschhorn
4p deletion, small, microcephaly, frontal bossing, cleft lip, heart defect, hypospadia (urethral issue), IQ less than 20, seizures, greek warrior helmet
Prader Willi
mostly small 15q deletion, but also a uniparental disomy (no paternal 15). obese
Angelman
mental retardation, microcephaly, jerky ataxic gait, maternal 15q deletion or UPD
Williams
elfin, music, cocktail party, supravalvular aortic stenosis, 7q11.12 elastin gene
22q11.2
DiGeorge/Velocardiofacial. CATCH22: Cardiac, Abnormal facies, Thymic aplasia, Cleft palate, Hypocalcemia/hypoparathyroidism.
Velocardiofacial has inadequate velopharyngeal closure, so difficulty speaking (hypernasal)
Miller-Dieker
Lissencephaly = smooth brain…defective neuronal migration. 17p13.3.
3 most common chromosomal abnormalities in spontaneous abortion
trisomies (esp 16), mono x, triploidy
Neuroblastoma
MycN
APL
15-17 translocation, take drug atra vit A thingy
AMmL
16inv
AMbL
8:21
Ewing
11:21 Ewing FLI1
Burkitt
Cmyc, 8:14 iG promoter
CML
Bcr Abl 9:22 imatinib gleevac Philly
Gastric
H Pylori
ALL
T/C cell 2nd most common
FAP
APC cin
HNPCC
MMR min….women more likely to have gyn malignancy not colon cancer
HPV
Cancer anywhere a penis could go. urogenital, oropharyngeal, ovarian, cervical…affects p53, rb
HBV/HCV
Hepatocarcinoma nFkb
EBV
lymphoma in immunosuppressed, also causes mono
hTLV1
nFkb/p53 T cell leukemia/lymphoma RNA virus
Asbestos
Mesothelioma ROS
Menangioma
mono 22
Alveolar rhabdo
2:13
Synovial sarcoma
X:18
retinal blastoma
del 13q14
Li Fraumeni
mutation p53
Atacia Telenglacia
DSB repair Ser/Thr kinase
BRCA1/2
DSB repair scaffold
Fanconi Anemia
x-link repair
Werner
wrn helicase cin
Bloom
blm butterfly malar rash helicase cin
Nij-Megan BS
DSB
Xeroderma Pigmentosum
NER
total risk congenital abnormality
2-3%
4 common congenital anomalies that increase likelihood of diagnosing a chromosome abnormality
Congenital heart defect, diaphragmatic hernia, omphalocele, cystic hygroma (turner)
3 maternal conditions that can cause fetal abnormalities
DM, epilepsy, congenital adrenal hyperplasia
First trimester/Second trimester screening
- pappA, nuchal translucency, hcg
2. AFP, hcg, estriol, inhibin
