Mrs Jones' First Consultation

Question 1

List the 7 types of congenital abnormalities and birth defects.

Answer 1

Malformation Disruption Dysplasia Sequence Association Deformation Syndrome

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Question 2

what is malformation?

Answer 2

• primary structural defect - involves a single organ showing multifactorial inheritance - due to both genetic and environmental factors

Question 3

what is disruption?

Answer 3

• this is secondary abnormal structure of an organ - caused by ischemia, infection and trauma - it is not geentic but genetic factors can pre dispose to it

Question 4

what is deformation?

Answer 4

• this is when a mechanical force distorts a structure - occurs is late pregnancy and the prognosis is usually good

Question 5

what is syndrome?

Answer 5

• this is a consistant pattern of abnormalities with a specific underlying cause - this includes chromosomal abnormalities

Question 6

what is sequence?

Answer 6

• multiple abnormalities initiated by a primary factor - this could have a genetic component as the initial factor and example is reduced amniotic fluid can lead to the potter sequence this is caused by oligohydraminios which is the reduced volume of amniotic fluid due to failure to produce urine.

Question 7

an example of sequence?

Answer 7

and example is reduced amniotic fluid can lead to the potter sequence this is caused by oligohydraminios which is the reduced volume of amniotic fluid due to failure to produce urine.

Question 8

Define dysplasia

Answer 8

Abnormal organisation of cells into tissue - caused by a single gene defect - there is high recurrence in siblings

Question 9

what is association?

Answer 9

• this is non random occurrence of abnormalities not explained by syndrome

Question 10

an example of association?

Answer 10

VACTERL association - Vertebral, Anal, Cardiac, Tracheo-Oesophagal, Renal, Limb

Question 11

What is the most common cause of Sequence e.g. Potter Sequence?

Answer 11

Oligohydramnios – reduced supply of amniotic fluid

Question 12

What are the 3 types of chromosome?

Answer 12

Metacentric Submetacentric Acrocentric

Question 13

Describe how chromosome banding works.

Answer 13

Starts at 11 at the centromere – different banding for different stains - the short arm is p and the long arm is q

Question 14

What are the three different types of chromosomal abnormality?

Answer 14

Aneuploidy Structural Mosaicism

Question 15

What is mosaicism?

Answer 15

The cells of an individual do not all contain identical chromosomes. There may be two or more genetically different populations of cells. E.g. one cell lineage will be Down Syndrome often the genetic disorder is not fully expressed

Question 16

what is the definition of autosomal aneuploidy?

Answer 16

• these are numerical abnormalities involving the loss or gain of one or more chromosomes

Question 17

what is partial aneuploidy?

Answer 17

• these are translocations of certain parts of chromosomes a derivative is a chromosome which looks like it has had a translocation

Question 18

What is the difference between a balanced and unbalanced translocation?

Answer 18

Unbalanced – there is a loss of genetic material (could result in non viable embryo) balanced - when there is a straight switch of the DNA no genetic material is lost

Question 19

What could be the potential future issues for someone who has a balanced translocation?

Answer 19

Balanced translocations lead to the formation of quadravalents (rather than bivalents) during meiosis which can lead to strange exchanges in genetic material which can cause disease

Question 20

List some clinical features of Down Syndrome

Answer 20

• Excess nuchal skin, (neck skin) - sleepy, - severe hypotonia,(less muscle tone) - Single palmar crease, - sandal gap (wide gap between first and second toes) - Upwards slanting eye folds, - macroglossia, (large tongue) - Short stature, - Cardiac abnormalities – ASD and VSD

Question 21

List three possible causes of Down syndrome.

Answer 21

• Non-disjunction ( failiure to separate) during meiosis I or meiosis II - (4%) Robertsonian translocation –2 acrocentric chromosomes break at the centromere and fuses to form a new chromosome (therefore has additional genetic material) - Mosaicism (1%)

Question 22

Name two other trisomy disorders

Answer 22

13 – patau syndrome, heart defects cleft lip mental retardation 18 – Edwards heart defects kidney malformation mental retardation

Question 23

What is monosomy X in females and what are the clinical features?

Answer 23

Turner Syndrome –1/3000 webbed neck, infertile, normal intelligence, Generalised oedema low posterior hairline 80% due to loss of X or Y chromosome in paternal meiosis.

Question 24

What is polysomy X in males and what are the clinical features?

Answer 24

Kleinfelter’s syndrome – tall, gynaecomastia, (enlargement of breasts) infertile, learning disability - clumsy comes from the X chromosome in either mother or father

Question 25

How can someone who has sex chromosomes XX be male? chromosome one gender and phenotypically another gender

Answer 25

Due to a translocation - the Y chromosome has the sex determining region on the Y - If there is a translocation of the SRY from the Y to the X you can get an X chromosome with a male determining factor and a Y that has LOST the male determining factor so phenotypically the XX will be male and the XY will be female.

Question 26

What are genomic disorders?

Answer 26

Disorders in which there is a gain or loss of DNA

Question 27

Give an examples of two genomic disorders

Answer 27

Deletion – Di George syndrome Duplication – Charcot-Marie-Tooth Disease Type 1A these are micro delation syndrome

Question 28

what is the human karyotype stained with?

Answer 28

giesma

Question 29

what is monosomy what is trisomy what is tetrasomy

Answer 29

loss of a single chromosome (always lethal) gain of a one chromosome ( can be tolerated) gain of two chromosomes ( can be tolerated)

Question 30

what happens when meiosis happens to someone with balanced translocation?

Answer 30

• when someone with balanced translocation undergoes meiosis their chromosomes will form a quadrivalent but it is normally a bivalent

Question 31

treatment of webbers syndrome?

Answer 31

oestrogen replacement for secondary sexual characteristics and prevention of osteoporosis.

Question 32

why is gain of chromosomes better tolerated than loss of chromosomes?

Answer 32

• if we lose a chromosome we have lost 50% of the gene pool - if we needed 100% of that chromosome this is very important - loss of an autosomal chromosome is almost always fatal

Question 33

what are diagnostic features of di- george syndrome?

Answer 33

• cardiac problems - hypoplastic thymus - Hypocalcaemia - lack of calcium in blood stream

Question 34

what happens in di george syndrome

Answer 34

Micro-deletion of 22q11.2 region containing the gene TBX1 this is delation of transcription factor

Question 35

what are diagnostic features in charcot marie tooth disease type 1A?

Answer 35

• Muscle weakness - hypotonia - missing reflexes - foot deformities

Question 36

what happens in charcot marie tooth disease?

Answer 36

• Micro-duplication of PMP22 gene on Chr 17 the deleted gene codes for membrane protein that is a major component of myelin