Genetics

Question 1

What is precision medicine

Answer 1

The idea that you can personalise treatment in order to get the best outcome
Using genetics etc you could identify the patients that would benefit from treatment and those that wouldn’t
Currently only available in some situations

Question 2

What is the earliest cutaneous sign of tuberous sclerosis

Answer 2

Ash-leaf macule

Hypopigmented macule in rough leaf shape

Question 3

What is a common first presentation of tuberous sclerosis

Answer 3

Infantile seizures

Question 4

What is a genodermatoses

Answer 4

Skin condition caused by a well defined genetic cause

Includes neurofibromatosis and tuberous sclerosis

Question 5

what are angiofibromas

Answer 5

Fibrous growth
Associated with tuberous sclerosis
Commonly seen in nasolabial folds

Question 6

What are some skin signs of tuberous sclerosis

Answer 6

Ash- leaf macule 
Cafe au lait macules
Angiofibroma - often facial 
Shagreen patches - areas of raised nodules and redness  
Periungal fibromas - around nails

Question 7

What are some non-skin related signs of tuberous sclerosis

Answer 7

Cortical tubers in brain - may cause seizures
Bone cysts
Enamel pitting in teeth
Hamartomas / angiomyolipomas in the heart, lung, kidneys

Question 8

What are the penetrance and expression patterns for tuberous sclerosis

Answer 8

Autosomal dominant
Penetrance is high
Still variable - some may not show features
Expression is variable so people are affected differently

Question 9

How does epidermolysis bullosa first present

Answer 9

Usually some skin trauma at birth
Progresses to blistering and skin loss - especially after movement or handling
However, blistering at birth doesn’t determine prognosis

Question 10

What is the mitten deformity

Answer 10

Common in epidermolysis bullosa
Repeated skin loss/trauma causes a lot of scarring (repeated healing)
This can cause tightening of the skin on the hands and lead to the fingers losing mobilty or becoming fused

Question 11

which genes are involved in epidermolysis bullosa

Answer 11

There are 10 genes
They are all involved in skin structure and adhesion
E.g. keratin 5, 14, integrins, collagen 17

Question 12

What is the dominant-negative disease mechanism

Answer 12

where the mutation still allows protein to be made but it doesn’t function properly
This abnormal polypeptide interferes
with the normal protein

Question 13

If parents are both carriers of a recessive gene, what is the risk of the child being affected

Answer 13

1 in 4

More likely in cases of incest

Question 14

What are café au lait macules

Answer 14

Pigmented brown macules
occur from birth onwards
Can be normal if only 1 or 2
If more than 5 it suggests a genetic disease

Question 15

What is a possible treatment for neurofibromas

Answer 15

MEK inhibitors

blocks the exaggerated pathway

Question 16

What is the role of the filaggrin gene

Answer 16

Important in maintaining the skin barrier

filament aggragating protein

Question 17

What condition occurs when there are mutations in the filaggrin gene

Answer 17

Ichthyosis vulgaris
Dry skin
Keratosis pilaris - bumps on back of arms
Wrinkled palms

Question 18

Which conditions does a filaggrin mutation increase your risk of getting

Answer 18

Eczema x4
Asthma and hay fever x3
Peanut allergy x5

Question 19

What type of inheritance is seen in NF type 1

Answer 19

Autosomal Dominant

Has variable penetrance. Chromosome 17 mutation

Question 20

List cutaneous features of NF type 1

Answer 20

Cafe au lait macules - 90% of cases
Neurofibromas
Axillary or inguinal freckling

Question 21

Neurofibromas tend to increase with age - true or false

Answer 21

True

Question 22

List non-cutaneous features of NF type 1

Answer 22

Optic glioma
2 or more Lisch nodules - dots in iris
Distinct bony lesions