Mrs Jones First consultation

Question 1

List the types of congenital abnormalities and categorise them according to their group

Answer 1

Single:
Malformation
Disruption
Deformation
Dysplasia

Multiple:
Sequence
Syndrome
Association

Question 2

What is the difference between Disruption and Malformation

Answer 2

Malformation is primary structural defect which usually involves a single organ e.g. cleft lip but disruption is extrinsic factor affecting normal development, e.g. digital amputation
Disruption is NOT genetic but malformation is both genetic and environmental

Question 3

What is deformation

Answer 3

Distortion of a structure by mechanical force, e.g. club foot

Question 4

Define dysplasia

Answer 4

Abnormal organisation of cells into tissue e.g. thanatophoric dysplasia
It is caused by a single gene defect

Question 5

What is the most common cause of Sequence?

Answer 5

Oligohydramnios – reduced supply of amniotic fluid e.g. potter’s sequence

Question 6

What is the difference between Sequence and Syndrome?

Answer 6

Syndrome- Consistent pattern of abnormalities with a specific underlying cause.
Sequence-multiple abnormalities initiated by primary factor, e.g. Potter’s sequence

Question 7

What is association and give an example

what is dysmorphism?

Answer 7

Dysmorphism – an unusual or abnormal physical feature (sometimes as part of a genetic syndrome), e.g. hypertelorism

Non-random occurrence of abnormalities NOT explained by syndrome or sequence. It is typically unknown e.g VATER association

Vertebral anomalies
Anal atresia
Cardiac defects
Tracheo-Oesophagal fitsula
 Renal/Radial anomalies
 Limb defects

Question 8

What are the 3 types of chromosome and what are there features?

Answer 8

Metacentric- centromere in the middle
Submetacentric- Centre more towards one side
Acrocentric-don’t have short arms (have satellites) A chromosome in which the centromere is located quite near one end of the chromosome. 5 chromosomes are acrocentric.

All human chromosomes have 2 arms, the p (short) arm and the q (long) arm

Question 9

Describe how chromosome banding works.

Answer 9

Starts at 11 at the centromere – different stains will give different numbers of bands.

Question 10

What are the three different types of chromosomal abnormality and their meaning

Answer 10

Aneuploidy- loss or gain,

Structural- translocation, deletions, insertions, inversions, rings( ends join together)

Mosaicism- different cell lineages.

Question 11

What is mosaicism?

Answer 11

Where different cells in the same individual have different numbers or arrangements of chromosomes

Question 12

What is the difference between a balanced and unbalanced translocation?

Answer 12

Unbalanced – there is a loss of genetic material, it can lead to a non-viable embryo.

Question 13

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

Answer 13

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 14

When is translocation a problem?

Answer 14

Disruption of a gene
or
Fusion product (Robertsonian translocation)

Question 15

List some clinical features of Down Syndrome

Answer 15

Excess nuchal skin, sleepy, severe hypotonia, Single palmar crease, sandal gap Upwards slanting eye folds, macroglossia: large tongue, Short stature, Cardiac abnormalities – ASD and VSD:Atrial septal defect (ASD) and ventricular septal defect
LOW IQ

Question 16

List three possible causes of Down syndrome.

Answer 16

Trisomy 21: Non-disjunction during meiosis I or meiosis II
Robertsonian translocation –2 acrocentric chromosomes break at the centromere and fusion of long arms to form a new chromosome
Mosaicism: causes by mitotic non-disjunction.

Question 17

Name two other trisomy disorders and the symptoms

Answer 17

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

Question 18

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

Answer 18

Turner Syndrome – webbed neck, infertile, normal intelligence, low posterior hairline, generalised oedema, , short 4th metacarpals, aorta defect in 15% of cases.short stature

80% due to loss of X or Y paternal meiosis

Question 19

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

Answer 19

Kleinfelter’s syndrome –
tall, gynaecomastia (30%)(enlargement of man’s breast), ALL infertile, learning disability
Increased risk of leg ulcers, osteoporosis and breast carcinoma in adult life.
X from mum or dad

Question 20

How can someone who has sex chromosomes XX be male?

Answer 20

Due to a translocation in which the sex determining region on the Y (SRY) has been translocated onto the X chromosome.

Question 21

What are genomic disorders?

Answer 21

Disorders in which there is a gain or loss of DNA

Question 22

Give example of a disorder caused by duplication and its diagnostic features

Answer 22

Charcot-Marie-Tooth disease type 1A
Muscle weakness, hypotonia, missing reflexes, foot deformitties- high arches or flat feet and lack of sensation in hands and arms.

Duplication of a gene which codes for an integral membrane protein that is a major component of myelin in the PNS.

Question 23

Why might genomic disorders not be visible in the karyotype?

Answer 23

these are micro-deletion syndromes e.g. Di George syndrome and Charcot-Marie-Tooth disease type 1A

Question 24

Give an example of a disorder caused by deletion and its diagnostic features?

Answer 24

Di George Syndrome
- Cardiac abnormalities
- Abnormal facies (widely spaced eyes, low set ears)
-Thymic hypoplasia
-Cleft palate
-Hypocalcaemia
-22
-difficulty feeding and learning difficulty
Micro-deletion of chromosome 22. In a gene that codes for a transcription factor involved in the regulation of many developmental processes

Question 25

what is dosage compensation

Answer 25

process by which organisms equalize expression of genes between members of different biological sexes