Genetics of dermatology

Question 1

What is a genedermatoses?

Answer 1

An inherited genetic skin condition

Question 2

What is the earliest cutaneous sign of tuberose sclerosis?

Answer 2

Ash-leaf macule

Question 3

Tuberose sclerosis may present as infantile seizures. T/F

Answer 3

True

Question 4

Is tuberose sclerosis autosomal dominant or recessive? What is the caveat to this?

Answer 4

Autosomal dominant. New mutations are common

Question 5

How may tuberose sclerosis present on the nails?

Answer 5

Periungual fibromata and longitudinal ridging

Question 6

How can ash leaf macules be “diagnosed”?

Answer 6

Wood’s lamp (may be depigmented or hyperpigmented)

Question 7

Which tumours are present in tuberose sclerosis?

Answer 7

Periungual fibromata, facial angiofibromas, cortical tumours ± calcification of falx cerebri, hamartomas of the heart, lungs and kidneys and bone cysts

Question 8

Which feature of tuberose sclerosis may lead to seizures?

Answer 8

Cortical tumours and/or calcification of the falx cerebri

Question 9

Angiofibromas decrease in size with age. T/F

Answer 9

False - they increase in size with age

Question 10

What are the miscellaneous signs of tuberose sclerosis?

Answer 10

Shagreen patches (overgrowth of connective tissue ± erythema) and enamel pitting

Question 11

Does tuberose sclerosis cause mental impairment?

Answer 11

It varies depending on presence/severity of tumours

Question 12

Which two genes are responsible for tuberose sclerosis? What is the term for this? What do they code for?

Answer 12

TSC1 & TSC2. Genetic heterogeneity. Tuberin & hamartin

Question 13

What does penetrance mean?

Answer 13

The degree to which a gene mutation manifests itself in a patient

Question 14

What are the feature of an autosomal dominant disease?

Answer 14

Disease is seen in all generations of a family, 50/50 risk to child if parent is affected, variable severity/penetrance, males and females equally likely to be affected

Question 15

What is a missense mutation?

Answer 15

A single change in nucleotide changes the amino acid being coded

Question 16

Deletion mutations can either be frameshift or non-frameshift. T/F

Answer 16

True

Question 17

Mutations can cause premature stops within the nuclotide sequence being coded for. T/F

Answer 17

True

Question 18

What type of inhibitor drug is helpful in tuberose sclerosis?

Answer 18

mTOR inhibitors

Question 19

What is epidermolysis bullosa?

Answer 19

A group of genetic skin fragility conditions

Question 20

What causes epidermolysis bullosa?

Answer 20

Through dominant, recessive or new mutations or it can be acquired

Question 21

The severity of the blistering of a baby with epidermolysis bullosa normally determines prognosis. T/F

Answer 21

False

Question 22

What are the three main types of epidermolysis bullosa?

Answer 22

Simplex, junctional and dystrophic

Question 23

What differentiates the different types of epidermolysis bullosa?

Answer 23

Simplex - epidermal
Junctional - DEJ
Dystrophic - dermis

Question 24

Which genes are involved in the development of epidermolysis bullosa?

Answer 24

Over ten genes linked to skin structure and adhesion (keratin, integrins, collagen, etc genes)

Question 25

What is epidermolysis bullosa aquisita?

Answer 25

A rare autoimmune conditon presenting later in life. Linked to autoantibodies to collagen 17

Question 26

How are keratin filaments normally assembled?

Answer 26

Types 1 and 2 keratins bond to form a dimer which goes on to bond with other dimers to form tetramers and then filaments

Question 27

What is a dominant-negative disease mechanism?

Answer 27

Mutated proteins cause normal proteins to stop working

Question 28

What is haploinsufficiency?

Answer 28

Mutation which reduces protein production (so less protein is made as only one allele is working)

Question 29

Haploinsufficiency always causes disease. T/F

Answer 29

False

Question 30

Gain of function mutations are always pathological. T/F

Answer 30

False

Question 31

No protein is produced when a mutation is autosomal recessive. T/F

Answer 31

True (providing the patient possesses both copies of the gene)

Question 32

What are the features of an autosomal recessive disease?

Answer 32

Most often only one generation affected, 1/4 risk of child getting condition if parents possess gene (inc. risk in consanguineous families)

Question 33

Which nerve does neurofibromatosis type 2 affect?

Answer 33

Auditory

Question 34

What are the features of neurofibromatosis type 1?

Answer 34

Cafe au lait macules, neurofibromas, flexiform neuroma, optic glioma, >2 lisch nodules, bony lesions

Question 35

What is flexiform neuroma?

Answer 35

Diffuse axillary or inguinal freckling

Question 36

Which inhibitory drug class can be used in the treatment of neurofibromatosis type 1?

Answer 36

MEK inhibitors

Question 37

What does the neurofibromine protein do?

Answer 37

Increases cell growth

Question 38

How does atopic eczema present?

Answer 38

Highly itchy, scaly, erythematous patches. Disturbed sleep pattern due to scatching

Question 39

Which traits contribute to the development of atopic eczema? Which of these is genetically influenced?

Answer 39

Skin barrier function, environmental agents & immunology. Skin barrier function & immunology.

Question 40

Mutations in flaggrin produce cause what clinical condition? How does this present?

Answer 40

Ichthyosis vulgaris. Fine scaling, keratosis pylaris & hyperlinearity

Question 41

What does flaggrin stand for?

Answer 41

Filament aggregating protein

Question 42

Flaggrin mutations are associated with higher risk of which conditions?

Answer 42

Eczema, asthma, hayfever and peanut allergy