1. Mrs Jones' first consultation

Question 1

Congenital abnormalities

Answer 1

Structural/ functional anomalies that occur during intrauterine life and can be identified prenatally, at birth or later in life

Question 2

List 5 causes of congenital abnormalities

Answer 2

Single gene defects
Chromosomal disorders
Multifactorial inheritance 
Environmental teratogens 
Micronutrient deficiencies

Question 3

Single congenital abnormalities- Malformation

Answer 3

Morphologic defect resulting from an intrinsically abnormal developmental process
e.g. cleft lip

Question 4

Single congenital abnormalities- Disruption

Answer 4

Morphologic defect resulting from extrinsic breakdown of/ interference with, an originally normal developmental process.
e.g. amniotic band causing digital amputation

Question 5

Single congenital abnormalities- Deformation

Answer 5

Abnormal form, shape or position of a part of the body caused by mechanical forces
e.g. Club foot

Question 6

Single congenital abnormalities- Dysplasia

Answer 6

An abnormal organisation of cells into tissue(s) and its morphologic results(s)
e.g. Thanatophoric dysplasia

Question 7

Multiple congenital abnormalities- Sequence

Answer 7

A pattern of multiple anomalies derived from a single known or presumed prior anomaly or mechanical factor
e.g. Potter sequence

Question 8

Multiple congenital abnormalities- Syndrome

Answer 8

Multiple anomalies thought to be pathogenetically related and not representing a sequence. Includes chromosomal abnormalities
e.g. Down syndrome

Question 9

Multiple congenital abnormalities- Association

Answer 9

A nonrandom occurrence in >,2 individuals of multiple congenital abnormalities not known to be a polytopic defect, sequence, or syndrome
e.g. VACTERL association Vertebral, Anal, Cardiac, Tracheo-Oesophagal, Renal, Limb

Question 10

Chromosome banding is written…

Answer 10

1. Chromosome number
2. P or Q arm
3. Band number

Question 11

Chromosome Abnormalities: Structural

Answer 11

Translocations
Deletions
Insertions

Question 12

Chromosome Abnormalities: Numerical

Answer 12

Monosomy = loss of a single chromosome, almost always lethal
Disomy = normal
Trisomy = gain of 1 chromosome, can be tolerated for specific chromosomes
Tetrasomy = gain of 2 chromosomes, can be tolerated for specific chromosomes

Question 13

Aneuploidy

Answer 13

loss or gain

Question 14

Chromosome Abnormalities: Mosaicism

Answer 14

different cell lineages, DON’T contain identical chromosomes

Question 15

Trisomy 21

Answer 15

Down syndrome

Question 16

Down syndrome age association

Answer 16

Higher maternal age = higher incidence

Question 17

List 4 Clinical Features of Down Syndrome- Cranial/ facial

Answer 17

Large tongue
Small ears
Epicanthic folds
Upward sloping palpebral fissues

Question 18

List 2 Clinical Features of Down Syndrome- Limbs

Answer 18

Single palmar crease

Wide gap between 1st and 2nd toes

Question 19

Clinical Features of Down Syndrome- Other

Answer 19

Short stature

Question 20

Non- disjunction

Answer 20

Failure to separate

Question 21

Majority of DS caused by

Answer 21

Non-disjunction during meiosis I and II

Question 22

4% of DS caused by

Answer 22

Translocations

Question 23

1% of DS caused by

Answer 23

Mosaicism

Question 24

Trisomy 13

Answer 24

Patau Syndrome

Question 25

List 3 characteristics of Patau Syndrome

Answer 25

Heart Defects
Holoprosencephaly (cleft lip/palate, hypotelorism)
Mental Retardation

Question 26

Trisomy 18

Answer 26

Edwards Syndrome

Question 27

List 4 characteristics of Edwards Syndrome

Answer 27

Heart defects
Kidney malformation
Digestive tract defects
Mental retardation

Question 28

Monosomy X- Females

Answer 28

Turner Syndrome

Question 29

Cause of majority of Turner syndrome cases

Answer 29

Loss of X or Y chromosome in paternal meiosis

Question 30

List 4 Characteristics of Turner Syndrome

Answer 30

Low posterior hairline
Webbed neck
Short stature
Ovarian failure

Question 31

Polysomy X - Males XXY

Answer 31

Kleinfelter’s Syndrome

Question 32

List 4 Characteristics of Kleinfelter’s Syndrome

Answer 32

Learning disability
Taller than average, long lower limbs
Enlargement of man’s breasts
All infertile

Question 33

Dosage compensation

Answer 33

Ensures equivalent gene expression in both sexes

Question 34

Dosage compensation mechanisms

Answer 34

1. Random inactivation of a single X chromosome in females
2. Increased (2x) expression of X chromosome genes in males
3. Decreased (0.5x) expression of both X chromosome genes in hermaphrodites

Question 35

XX

Answer 35

Female

Question 36

XY

Answer 36

Male

Question 37

Deletion syndrome example

Answer 37

Di George Syndrome

Question 38

Duplication syndrome example

Answer 38

Charcot-Marie-Tooth disease type 1A

Question 39

Di George Syndrome:

List 5 Diagnostic Features

Answer 39

Cardiac abnormalities 
Abnormal facies
Thymic Hypoplasia
Cleft palate
Hypocalcaemia

Question 40

Di George:

Micro-deletion

Answer 40

22q11.2 region containing the gene TBX1

Question 41

Charcot-Marie-Tooth disease type 1A:

List 5 Diagnostic Features

Answer 41

Muscle weakness
Hypotonia
Missing reflexes
Foot deformities - high arches or flat feet 
Lack of sensation in hands and arms

Question 42

Charcot-Marie-Tooth disease type 1A:

Micro duplication

Answer 42

PMP22 gene on Chr 17