1 - Mrs Jones' first consultation

Question 1

Define terategen

Answer 1

an agent that interferes with the normal embryonic or foetal development

Question 2

What is a malformation?

Give an example

Answer 2

a primary structural defect
usually involves a single organ showing multifactorial inheritance
e.g. atrial septic defects, cleft lip

Question 3

Define disruption

give an example

Answer 3

a secondary structural defect of an organ/tissue
usually cause by ischaemia, infection or trauma
NOT GENETIC
e.g. amniotic band causing digital amputation

Question 4

Define deformation

give an example

Answer 4

abnormal mechanical force distorting a structure
usually occurs later in pregnancy, but has a good prognosis because the underlying structure is normal
e.g. clubbed foot, hip dislocation

Question 5

Define dysplasia

give an example

Answer 5

abnormal organisation of cells into tissues
e.g. thanatophoric dysplasia - short flat bones, small thorax, large head
caused by a single gene defect

Question 6

What are the 4 single congenital abnormalities?

Answer 6

malformation
disfunction
deformation
dysplasia

Question 7

What are the 3 multiple congenital abnormalities?

Answer 7

syndrome
sequence
association

Question 8

Define syndrome

give an example

Answer 8

consistent pattern of abnormalities with a specific underlying cause
e.g. Down’s syndrome
(this includes chromosome abnormalities)

Question 9

Define sequence

give an example

Answer 9

multiple abnormalities initiated by a primary factors

e.g. reduced amniotic fluid leads to Potters Sequence (this is due to oligohydramnios)

Question 10

Define association

give an example

Answer 10

non-randomised occurrence of abnormalities NOT explained by a syndrome
unknown cause
e.g. VATERL association

Question 11

What re the types of chromosome abnormalities?

Answer 11

aneuploidy
structural
mosaicism

Question 12

What is aneuploidy?

Answer 12

loss of gain of chromosomes

numerical abnormality

Question 13

give some examples of structural abnormalities

Answer 13

translocation
deletion
insertion
inversions
rings

Question 14

What is mosaicism?

What is the cause?

Answer 14

cells in the same person have different genes/cell lineages

caused by mitotic disjunction

Question 15

What are the subtypes of autosomal aneuploidy?

Why can be tolerated and which are lethal?

Answer 15

• monosomy - loss of a single chromosome (always lethal)
• trisomy - gain of one chromosome (can be tolerated)
• tetrasomy - gain of two chromosomes (can be tolerate)

Question 16

What is meant by disomy?

Answer 16

normal number of chromosomes

Question 17

What happens in a balanced translocation?

Answer 17

there is a straight switch of sections of DNA, so no genetic material is lost

Question 18

What happens in an unbalanced translocation?

Answer 18

genetic material is lost (this could result in a non-viable embryo)

Question 19

What is a derivative?

Answer 19

a chromes that looks like it has had a translocation

Question 20

What is the main cause of Down’s syndrome?

Answer 20

trisomy 21
75% = non-disjunction during meiosis I
25% = during meiosis II

Question 21

Give some clinical features of Down’s:

1) newborn period
2) craniofacial
3) limbs
4) cardiac
5) other

Answer 21

1) severe hypotonia, excess nuchal skin
2) macroglossia, small ears, epicanthic folds, Brushfield spots
3) single palmar crease, sandal gap
4) atrial and ventricular septal defects
5) short stature, duodenal atresia

Question 22

Why are children who have Down’s through mosaicism less affected than those who have Down’s through the other 2 causes?

Answer 22

the non-disjunction has been carried out during mitosis in mosaicism

Question 23

What is the main cause of Turner’s syndrome?

Answer 23

monosomy X

Question 24

What are the other causes of Turner’s syndrome?

Answer 24

ring chromosome
single arm deletion
mosaicism

Question 25

What is the main cause of Klinefelter’s syndrome?

Answer 25

47, XXY

Question 26

What is the usual phenotype gender for someone with Klinefelter’s?

Answer 26

male

Question 27

What is dosage compensation?

How is this achieved?

Answer 27

a mechanism by which the expression of X-linked traits is equalized in males, which have one X chromosome, and females, which have two. This ensures there is equivalent expression in both males and females.
In mammals it is accomplished by the random inactivation of one of the X chromosomes in the somatic cells of females.

Question 28

What are the 3 mechanisms of dosage compensation?

Answer 28

1 - Random inactivation of a single X chromosome in females (most mammals) – lyonization, formation of Barr bodies
2 - Increased (2x) expression of X chromosome genes in males
3 - Decreased (0.5x) expression of both X chromosome genes in hermaphrodites

Question 29

How is it possible to be genotypically/chromosomally one gene and phenotypically the opposite?

Answer 29

due to translocation
the sex determining region of the Y (SRY) can undergo recombination/translocation
it can move from the Y chromosome to the X: so the X chromosome has a male determining factor
(phenotypically, the XX will be a male and XY will be a female)

Question 30

What causes genomic disorders?

Answer 30

loss or gain of DNA

Question 31

What type of genomic disorder may not be visible in the karyotype?

Answer 31

micro-deletions

Question 32

LO: identify 2 common autosomal and 2 common sex chromosome aneuploidies?

Answer 32

AUTOSOMAL:
- trisomy 13 - Patau's syndrome
- trisomy 18 - Edward's syndrome
(both cause heart defects)
SEX CHROMOSOMES:
- Turner's
- Klinefelter's

Question 33

LO: list 2 examples of genetic disorders and describe their clinical features

Answer 33

DI GEORGE SYNDROME
(caused by micro-deletion)
- cardiac abnormalities
- abnormal facies (low set ears, widely-spaced eyes)
- thymic hypoplasia
- cleft palate
- hypocalcaemia
CHARCOT-MARIE-TOOTH DISEASE
- muscle weakness
- foot deformities
- foot drop
- hypotonia
- missing reflexes
- lack of sensation in arms and hands