Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Genetics of Learning Disorders > Clinical Aspects of Chromosome Disorders > Flashcards

Clinical Aspects of Chromosome Disorders Flashcards

You may prefer our related Brainscape-certified flashcards:
Biology 101 flashcards
1
Q

What features might you expect a patient to have if they were said to ‘look chromosomal’?

A
  • Developmental delay
  • Low birth weight
  • Failure to thrive
  • Microcephaly
  • Dysmorphic face
  • Ear malformations, puts
  • Transverse palmar crease
  • Overlapping toes
  • Cerebral, cardiac, G-U malformation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Describe the possible indications for chromosome analysis.

A

2 or more of the following criteria:

  • Developmental delay
  • IUGR/Failure to thrive
  • Microcephaly
  • Facial dysmorphism
  • Multiple congenital malformations
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

List the possible different types of chromosome abnormalities.

A
  • Polyploidy (usually triploidy)
  • Autosomal trisomies (21, 18, 13)
  • Sex chromosome abnormalities
  • Deletions/duplications/inversions/ring chromosomes
  • Translocations (Robertsonian/reciprocal)
  • Mosaicism
  • UPD
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

List some of the most common chromosomal abnormalities.

A
  • Down Syndrome (47XX or XY, +21)
  • Klinefelter Syndrome (47XXY)
  • Turner Syndrome (45X)
  • Edward Syndrome (47XX or XY, +18)
  • Patau Syndrome (47XX or XY, +13)
  • Autosomal Deletion or Duplication Syndrome
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are some of the characteristic features seen in Down syndrome?

A
  • Up-slanting palebral fissures
  • Epicanthic folds
  • Brachycephaly
  • Small simple ears
  • Large tongue
  • Sandle gap toes
  • Brush field spots in the iris
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the incidence of Down syndrome?

A

Down syndrome occurs in about 1 in 650 births and is associated with increased maternal age.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is down syndrome usually caused by?

A

Nondisjunction events at meiosis (95%). A smaller number are due to translocations (4%) and 1% are mosaic.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What percentage of individuals with Down syndrome survive to 10 years?

A

About 85% and survival is increasing.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is the risk of having a child affected at Down syndrome at all ages?

A

1 in 650

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is the risk of a woman having a child affected with Down syndrome at 20 years of age?

A

1 in 1500

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is the risk of a woman having a child affected with Down syndrome at 30 years of age?

A

1 in 800

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is the risk of a woman having a child affected with Down syndrome at 35 years of age?

A

1 in 270

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Which of the chromosomes are acrocentric?

A

13, 14, 15, 21, 22

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is the recurrence risk of Down syndrome if the mother is young and it is due to standard non-disjunction?

A

1% (for any chromosome abnormality)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the recurrence risk of Down syndrome if the mother is a 14/21 translocation carrier?

A

10%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is the recurrence risk of Down syndrome if the father is a 14/21 translocation carrier?

A

2%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is the recurrence risk of Down syndrome if either parent is a 21/21 translocation carrier?

A

100%

18
Q

What are the features of Edward syndrome?

A

Trisomy 18. The incidence is 1 in 5,000 and this is increased with increased maternal age. Features include intra-uterine growth retardation, failure to thrive, severe mental retardation, rocker bottom feet. 90% of babies with Edward syndrome die by one year.

19
Q

Describe some of the features of Patau syndrome.

A

Patau syndrom results from trisomy 13. The incidence is 1 in 12,000 and this is increased with increased maternal age. Individuals with Patau syndrome have severe mental retardation. About 80% of babies with Patau syndrome die by one year of age.

20
Q

What are the main sex chromosome abnormalities?

A
  • Turner syndrome - 45,X - may be mosaic with 45X/46XX, 45X/47,XXX, or 45X/46,XY
  • Triple X
  • Klinefelter Syndrome
  • XYY
21
Q

Describe Pallister-Killan Syndrome.

A

Pallister-Killan Syndrome is a mosaic tetrasomy of 12p. It is a sever condition characterised by:

  • Profound mental retardation
  • Sparse temporal hair
  • Coarse face
  • Thin upper lip, downturned mouth
  • Low set fleshy ears
  • Supernumerary nipples, caudal appendage
  • Diaphragmatic defects
  • May be present only in cultured fibroblasts
22
Q

What features might you expect an individual with mosaicism for trisomy 14 to display?

A
  • Pigmentation along Blashko’s lines

- Asymmetry

23
Q

What microdeletion is involved in Angelman/Prader-Willi syndrome?

A

Angelman/Prader-Willi = 15q11-13

24
Q

What microdeletion is involved in Williams Syndrome?

A

Williams syndrome (elastin gene) = 7q11.23

25
Q

What microdeletion is involved in Velo-cardio-facial/Shprintzen Syndrome?

A

Velo-cardio-facial/Shprintzen Syndrome = 22q11

26
Q

What microdeletion is involved in Rubinstein-Taybi Syndrome?

A

Rubinstein-Taybi Syndrome = 16p13.3

27
Q

What microdeletion is involved in Miller-Dieker Syndrome?

A

Miller-Dieker Syndrome = 17p13.3

28
Q

What microdeletion is involved in Smith-Magensis Syndrome?

A

Smith-Magensis Syndrome = 17p11.2

29
Q

What microdeletion is involved in Langer-Giedion Syndrome?

A

Langer-Giedion Syndrome = 8q24.1

30
Q

What microdeletion is involved in WAGR Syndrome?

A

WAGR = 11p13

31
Q

List some known microdeletion syndromes.

A
  • Angelman/Prader-Willi = 15q11-13
  • Williams syndrome (elastin gene) = 7q11.23
  • Velo-cardio-facial/Shprintzen Syndrome = 22q11
  • Rubinstein-Taybi Syndrome = 16p13.3
  • Miller-Dieker Syndrome = 17p13.3
  • Smith-Magensis Syndrome = 17p11.2
  • Langer-Giedion Syndrome = 8q24.1
  • WAGR = 11p13
  • 1p36 deletion
32
Q

How might you test for a microdeletion syndrome?

A

Using FISH probes.

33
Q

Describe the features of Williams syndrome.

A

Williams syndrome involves an Elastin gene deletion at 7q11 in 90% of patients. Individuals may present with the following:

  • Feeding problems
  • Hypercalcaemia
  • Heart defects such as supravalvular aortic stenosis and multiple peripheral pulmonary artery stenosis
  • Full cheeks, stellate iris pattern
  • Dev delay, cocktail party manner
  • Growth retardation
  • Renal abnormalities
34
Q

Describe the features of Velo-Cardio-Facial Syndrome (Shprintzen Syndrome).

A
  • 22q11 deletion which can be detected using FISH.
  • Features include cleft palate, nasal voice, prominant nose with bulbous tip, almond shaped eyes, round ears with overfolded helices and long fingers and toes.
  • Outflow tract heart defects including Fallot’s and truncus/coarctation.
  • Mild mental retardation/psychosis
35
Q

Describe the features of Smith-Magenis syndrome.

A

Smith-Magenis syndrome involves the deletion of 17p11.2. The features include the following:

  • Dev delay, especially speech, hoarse voice.
  • Behavioural problems, self-destructive, self-hugging.
  • Sleep disorder, absent REM sleep.
  • Short stature, small hands and feet.
  • Brachycephaly, broad square face, heavy brows with lateral extension, USPF, fleshy central upper lip.
  • Scoliosis, deafness, strabismus, myopia, heart defects, GU malf, hypothyroidism, immune deformation.
36
Q

What percentage of mental retardation is thought to be due to cryptic telomeric translocations?

A

6% of unexplained mental retardation is due to a cryptic telomeric rearrangement. Multi probe system allows for testing of each telomere using FISH.

37
Q

Describe the features of 1p36.3 deletion syndrome.

A
  • Retarded growth and development
  • Deep-set eyes, neat horizontal eyebrows
  • Cleft lip and palate
  • Microcephaly
  • Delayed fontanelle closure
  • Severe mental retardation, epilepsy, cerebral atrophy
  • Congenital heart disease including Ebstein anomaly and cardiomyopathy
38
Q

What has superseded FISH testing for some micro deletion syndromes?

A

Microarray analysis has replaced many forms of chromosome testing. This testing essentially sweeps the entire genome for DNA chunks that are either missing or have been duplicated (copy number variation).

A benefit over FISH is that the use of arrays requires no prior knowledge of the case and/or chromosomal region of interest.

Currently this picks up abnormalities in around 20% of those with normal karyotype who fulfil testing criteria.

As technology improves this figure is likely to increase.

39
Q

What are the selection criteria used to select which patients should be selected for genetic testing for chromosomal abnormalities?

A

Patients are currently selected by Clinical Geneticists but testing is likely to become more mainstream.

Selection criteria include:

  • Unexplained developmental delay or learning difficulties of at least moderate severity and…
  • Facial dysmorphism and/or….
  • Growth problems or….
  • One or more major congenital abnormality or….
  • Behaviour problems such as autism.
40
Q

How does array CGH distinguish duplications from deletions?

A
  • Equal hybridisation gives 1:1 ratio of ret to green.
  • Deletion gives excess of control DNA sample colour.
  • Duplication gives excess of patient DNA sample colour.
  • If the green/red ratios are plotted, equal hybridisation will be 1.0, ratios indicating reduced patient DNA will fall between 0 and 1.0, whilst ratios showing excess patient DNA will be greater than 1.0 (and potentially could be 3 for trisomic/monosomic, or even higher). This means that the plot is asymmetrical.
41
Q

What is the risk of a woman having a child affected with Down syndrome at 40 years of age?

A

1 in 100.

42
Q

What is the risk of a woman having a child affected with Down syndrome at 45 years of age?

A

1 in 50 or greater.

Genetics of Learning Disorders (10 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions