Chromosomal Abnormalities: Autosome Errors

Question 1

Nondisjunction

Answer 1

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}

Question 2

Mosaicism

Answer 2

The presence of multiple genetically different cell lines derived from a single zygote.

Results from post-zygotic mitotic nondisjunction

Question 3

When to suspect a chromosomal abnormality

Answer 3

Growth restriction

Structural abnormalities, esp multiple

Developmental delay or mental incapacity

Question 4

Causes of trisomies

Answer 4

• Nondisjunction
  
  • Risk factor: older mom
• Translocation

Question 5

How does the risk of down syndrome increase as the mom ages from 35 to 40?

Answer 5

Question 6

Most of the nondisjunction that occurs with advanced maternal age occurs when?

Answer 6

in meiosis I

Question 7

Most common translocation is ____ and it can cause Down syndrome.

Answer 7

Robertsonian 14;21 translocation

Question 8

Does this child have trisomy 21 due to extra chromosome or is this a carrier of a 14,21 robertsonian translocation?

Answer 8

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.

Question 9

Someone who has translocation down syndrome usually has had several miscarriages. Why?

Answer 9

The other possibilities where one of the parents is a carrier are unviable (e.g. monosomy 21, trisomy/monosomy 14)

Question 10

Recurrence risk for down syndrome?

Answer 10

• 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%

Question 11

For all translcoations, the risk to the subsequent offspring is alwyas higher if

Answer 11

the mom was the carrier

if it’s the dad, then it often end up being a alternate/balanced translocation

Question 12

Trisomy of any autosomes will cause miscarriages except for which ones?

Monosomy of any autosomes will cause miscarriages except for which ones?

Answer 12

Trisomy 13, 18, 21 can be viable

NO MONOSOMIES of autosomes are viable

exception: mosaics

Question 13

95% of down syndrome is due to ___

4% due to __

1-2% due to __

Answer 13

95% due to free trisomy 21

4% due to robertsonian translocation

1-2% due to mosaic trisomy

Question 14

Down syndrome abnormalities/symptoms you see as a child

Answer 14

Big things:

• intellectual disability
• epicanthal folds
• duodenal atresia
• macroglossia (big tongue)
• flat face

Question 15

Down syndrome issues that you see as children grow up

Answer 15

Question 16

How long do down syndrome patients survive til and what is their major morbidity caused by?

What is treatment?

Answer 16

Question 17

Trisomy 18 (Edwards) abnormalities

Answer 17

• 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

Question 18

Survival of trisomy 18 (edwards)

Answer 18

only 10% make it to 1 year with severe mental incapacity and poor growth

Question 19

Trisomy 13 (Patau) abnormalities

Answer 19

• 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

Question 20

rank the rarity of trisomy 13, 18, and 21

Answer 20

13 rarest -> 18 -> 12

Question 21

Patau syndrome (13) survival

Answer 21

like 18, only about 15% survive beyond the first year

severe mental/physical abnormalities

Question 22

Triploidy

What is it and what is it an example of?

Answer 22

Extra set of chromosomes (23) –> 69 total chromosomes

• example of imprinting - different phenotype if the extra set is from the mother or the father

Question 23

Crit du Chat - what is it?

Answer 23

5p-

Deletion of the petite arm of Chromsome 5

Question 24

Crit du Chat abnormalities

Answer 24

Characteristic cry of a cat as a newborn!

• failure to thrive
• developmental delay
• hypotonia
• small face, large nose, large mouth