Chromosomal Abnormalities: Autosome Errors Flashcards
Nondisjunction
2 homologous chromosomes fail to separate in meosis I
OR
2 chromatids of a chromsome fail to separate in meiosis II or mitosis
when in doubt, it’s nondisjunction
Mosaicism
The presence of multiple genetically different cell lines derived from a single zygote.
Results from post-zygotic mitotic nondisjunction
When to suspect a chromosomal abnormality
Growth restriction
Structural abnormalities, esp multiple
Developmental delay or mental incapacity
Causes of trisomies
-
Nondisjunction
- Risk factor: older mom
- Translocation
How does the risk of down syndrome increase as the mom ages from 35 to 40?
Most of the nondisjunction that occurs with advanced maternal age occurs when?
in meiosis I
Most common translocation is ____ and it can cause Down syndrome.
Robertsonian 14;21 translocation
Does this child have trisomy 21 due to extra chromosome or is this a carrier of a 14,21 robertsonian translocation?
Even though they have 46 chromosomes, they have 3 copies of 21 material , one of them ebing on the chromosome 14 –> trisomy 21 due to 14,21 robertsonian translocation
You can see one of the 21 copies are on that right 14.
Someone who has translocation down syndrome usually has had several miscarriages. Why?
The other possibilities where one of the parents is a carrier are unviable (e.g. monosomy 21, trisomy/monosomy 14)
Recurrence risk for down syndrome?
- If it’s free trisomy 21 (due to nondisjunction), the recurrence risk is 1% until ~age 40, then it becomes an age-related risk
- If it’s a 14;21 Robertsonian translocation, then it depends-
- both normal parents (translocation was di novo), then the chance of recurrence is not significantly higher
- maternal carrier: 10-15%
- paternal carrier: 3-5%
For all translcoations, the risk to the subsequent offspring is alwyas higher if
the mom was the carrier
if it’s the dad, then it often end up being a alternate/balanced translocation
Trisomy of any autosomes will cause miscarriages except for which ones?
Monosomy of any autosomes will cause miscarriages except for which ones?
Trisomy 13, 18, 21 can be viable
NO MONOSOMIES of autosomes are viable
exception: mosaics
95% of down syndrome is due to ___
4% due to __
1-2% due to __
95% due to free trisomy 21
4% due to robertsonian translocation
1-2% due to mosaic trisomy
Down syndrome abnormalities/symptoms you see as a child
Big things:
- intellectual disability
- epicanthal folds
- duodenal atresia
- macroglossia (big tongue)
- flat face
Down syndrome issues that you see as children grow up
How long do down syndrome patients survive til and what is their major morbidity caused by?
What is treatment?
Trisomy 18 (Edwards) abnormalities
- Pre- and postnatal growth deficiency
- Microcephaly, prominent occiput, low set ears, rocky bottom feet
- Clenched hands (index finger overlies 3rd finger)
-
More severe congenital heart diseases (over 90%)
- Ex) tetralogy of Fallot, coarctation of the aorta, anomalous coronary arteries, transposition of the great vessels
Trisomy 13 (Patau) abnormalities
- Holoprosencephaly
- Severe intellectual deficiency
- Midline cleft lip/palate (70%)
- Abnormal ears
- Scalp defects (aplasia cutis)
- Polydactylyl (postaxial)
- Congenital heart abnormalities (80%): VSD, patent ductus arteriosus, ASD
- Single umbilical artery
- Omphalocele
- hypogonadism
Triploidy
What is it and what is it an example of?
Extra set of chromosomes (23) –> 69 total chromosomes
- example of imprinting - different phenotype if the extra set is from the mother or the father
Crit du Chat abnormalities
Characteristic cry of a cat as a newborn!
- failure to thrive
- developmental delay
- hypotonia
- small face, large nose, large mouth
