Chromosomal Defects Flashcards
About a 1/3 of congential defects are:
heart defects
hCG is coming from:
syncio something
what are non invasive tests that are performed routinely on pregnant women
maternal serum screen at 15-20 weeks of gestation
you have an inc risk of trisomy 21 if you have ___AFP, ____uE2 but ____hGC
low; low; high
you have an inc risk of trisomy 18 if you have ____ AFP, ____uE2, and ____ hCG
low; low low
if you have an inc risk of neural tube defect than you will have ____ AFP, ____ u#2 and ____ hCG
high; normal; normal
____ is a structural defect of any type
anomaly
_____ is intrinsic and related to a genetic disorder
malformation
____ is extrinsic and is related to a mechanical disorder
deformation; trauma or constraint (multiple fetuses, amniotic bands)
___ is extrnsic and related to teratogen exposure
disruption
____refers to multiple anomalies that occur independently, but are caused by a single defect
syndrome; marfan
_____is when a structural or mechanical factor leads to multiple secondary effects
sequence; low amniotic fluid
what are ex of multifactorial disorders
hypertension, cardiovascular disease, coronary artery disease, IDDM, some forms of cancer; combination of genetics + env factors that give you phenotypical expression
What is the eqn for heritability
G/G+B+E =G/V G=genetic B= familial env E= random env V= total variance
what are features of multifactorial disorders
- disorders that run in families
- no single gene/chromosomal abnormality is responsible
- a comb of genetics and env factors req for phenotypic expression
- dont follow mendelian patterns of inheritance
what doesn’t close properly in spina bifida
rostral/caudal neuropore; due to lack of folate
what are some dev defects that can contribute to multifactorial disorders
- congenital heart defects
- spina bifida
- anencephaly (rostral neuropore not closing properly)
- cleft palate (palatine shelves not fusing properly)
what things contribute to most birth defects that we see
- alcohol
- tobacco
- retinoic acid (Vit A excess)
- dilantin (anti seizure drug)
- decrease in folate
what are features of whole chromosomal disorders
- incompatible with life (spontaneous abortion
- rarely reproduce
- most directly linked to maternal age
- may occur in autosomes or sex chromosomes
- detectable via karyotype analysis
What is XO abnormality
Turner syndrome: True monosomy (just one sex chromosome) not very harsh but see it at a 10 fold lower incidence
what is the trend seen in autosomal abnormalities
incidence goes down with severity of disease
Triplet embryo is a live birth via polyspermy
which sex chromosomal abnormalities are in newborns are about 1/1000
- Klinefelter: XXY
- XYY: supermale; usually tall, some autism
- XXX : superfemale
Usually see a trisomy at which chromosomes
13, 18, 21 (gene dosage affect)
what is the most common trisomy in aborted fetuses
trisomy 16
What are 2 ways you can get nondisjunction
Meiosis 1: Tetrads dont disjoin properly so all 4 copies go to daughter cell and disjoin in next meiosis
Meiosis 2: sister chromatids dont disjoin in second meotic division and both go to 1 daughter cell.
-This event leads to uniparental disomy. In trisomy, during cleavae stages One chromosme will be lost in a div so daughter cell wont have an extra chromosme (normal dipoloid complement). every cell in this embryo that arises from this daughter cell is normal so you get mosaicism, where an embryo is derived from 2 genetically derived pop’s of cells (one with normal diploid complement, one with trisomy) which influences severity of disease.
What are some things that are obvious in uniparental disomy
- If this chromosome houses cystic fibrosis mutaiton and you have both copies from parent with mutation you can get disease without having two carrier parents.
- IIf imprinted region and your meant to have a copy form mom and dad to compensate from each other you can get Prader Willi or Angelmans without having a deletion.
what are characteristics of Klinefelter syndrome
- tall
- low IQ
- infertile
- hypogonadism
- gynecomastia
what are characteristics of tuner syndrome
- short
- infertile
- issues with aorta
- round moles
- webbing around neck
- underdev breast and nipples are really apart
- no IQ issues
- 25% mosaics
what is fragile X syndrome:
Major cause of mental retardation
1. Has extra GCC repeat in 5; UTR of FMRI gene
> 230 repeats = FMR1 silenced via methylation
2. macro orchidism
3. dental crowding
what are the three autosomal aneuploidies:
Trisomies:
13: Patau
18: edward
21: down
* true autosomal monosomies are not found, they’re lethal.
If mosaics, disease is not going to be as severe because they have a subpop of their bodies that are made up of _____ cells. 4% are translocations
normal
What are clinical features of trisomy 21
- hypotonia (not good body control)
- mental retardation
- epicanthic folds
- simian creases
- short stature
- forrowed tongue
- heart defects
- predisposition for leukemia
- brushfield spots on iris
- gap between toe
- neurofibrillary tangles
- duodenal obstruction
what are clinical features of trisomy 18 (edward)
- mental retardation
- rocker bottom feet
- malformed ears
- hypoplastic nails
- rarely survive past infancy
what are clinical features of trisomy 13:
- lethal by 6 mo
- severe CNS malformations
- cleft lip/palate
- holoprosencephaly
what are structural abnormalities
- deletions;
- Duplications
- Inversions; deliterious if breakpoint is within a gene
- Translocations
What are ex of deletions (partial monosomies) and what are they caused by
chromosomal breaks;
- Cri du chat
- Prader Willi/Angelman
what are clinical features of cri du chat syndrome
- 5 p deletion
- microcephaly
- micrognathia
- hypertelorism
- malformed ears
- severe retardation
translocation bet chromosomes 9 and 22 produce a fusion gene comprised of the ____ oncogene and 5’ portion of the Bcr gene and results in a fusion protein that contributes to dev of chronic myeloid leukemia
Abl
A robertsonian translocation is between two ___ chromosomes and is associated with a familial form of Down sydrome
acrocentric; the centromere is very near the end of a chromosme
what are teratogens
drugs/chemicals/infectious agents that may adversely affect fetal dev.
what factors affect the outcome of teratogen exposure
- time of exposure (the earlier exposed, the worst)
- dosage
- fetal/maternal genotype.
what are ex of some teratogens
- thalidomide
- retinoic acid (accutane)
- alcohol
- hydantoin (dilantin)
What are ex of other teratogens
- ACE inhibitors (for BP): kidney defects in 2, 3 trimester
- antineoplastic agents; severe
- mercury: neurotoxin, cerebral palsy like syndrome
- Warfarin (clotting agent), lithium, tobacco
- lack of morphogen: folate; critical for neural tube dev
week___ is most crucial for dev
3-8
what kind of cartilage do you get from 1st and 2nd pharyngeal arch?
- meckels and richords (make bones of ear)
What does maternal vit A deficiency lead to
- small eyes (micropthalmia)
- cleft palate/lip
- cardiovascular
- urogenital anomolies
- malformed limbs
what does fetal alcohol syndrome lead to
- mental retardation
- skeletal defects
- growth retardation
- heart defects
.5 smooth philtrum
1 in 6 have cleft palates
what are features of fetal hydantoin sydrome
- craniofacial anomalies
- growth retardation
- mental retardation
- limb defects
* degree of severity is linked to low activity form of epoxide hydrolase ( enzyme in liver that metabolizes this drug) in mother
what does TORCH stand for
- toxoplasmosis: parasite found in cats, can get hydrocephalus
- other: HIV, Syphillis (bacteria), VZV (chicken pox)
- rubella: german measles (blindness, cataracts)
- CMV: benign infection in adult that can have horrible issues in dev fetus
- HSV: herpes virus that doesnt cross fetal membrane but if infection, baby can acquire it
what are maternal preexisting conditions that can cause defects in infants
- diabetes mellitus: CV defects, CNS defects
2. Phenylketonuria: microcephaly, congenital heart defects, retardation
