Genetics

Question 1

what is tuberose sclerosis?

Answer 1

a rare multi-system genetic disease that causes benign tumors to grow in the brain and on other vital organs such as the kidneys, heart, eyes, lungs, and skin. one of the most common genodermatoses.

Question 2

what might tuberose sclerosis present as in infants?

Answer 2

infantile seizures

Question 3

what is the earliest cutaneous sign?

Answer 3

ash-leaf macules

Question 4

what type of mutation is tuberose sclerosis?

Answer 4

autosomal dominant but new mutations are common

Question 5

what do ash-leaf macules look like?

Answer 5

depigmented macules

Question 6

what can be used to make ash-leaf macules more visible?

Answer 6

a wood’s lamp

Question 7

what tumours are found in tuberose sclerosis?

Answer 7

periungual fibromas
facial angiofibromas cortical tubers &/or calcification of falx cerebri
hamartomas (angiomyolipomas)
bone cysts

Question 8

when do angiofibromas start to develop in tuberose sclerosis?

Answer 8

in the first few years of life

Question 9

what other skin signs are present in tuberose sclerosis?

Answer 9

shagreen patches

enamel pitting

Question 10

what can cortical tubers cause in tuberose sclerosis?

Answer 10

epilepsy & varying degrees of mental impairment

Question 11

what do the affected genes code for in tuberose sclerosis?

Answer 11

tuberin & hamartin

Question 12

what is epidermolysis bullosa (EB)?

Answer 12

a group of genetic skin fragility conditions of varying severity

Question 13

what type of mutations are present in EB?

Answer 13

can be dominant, recessive, new mutations or acquired

Question 14

what does simplex EB affect?

Answer 14

affects keratinocytes binding together, blisters at sites of trauma

Question 15

what does junctional EB affect?

Answer 15

affects proteins in DEJ

Question 16

what does dystrophic EB affect?

Answer 16

affects the dermis and the organisation of the proteins within it, skin is progressively shed and replaced by more and more scarring

Question 17

how many genes are involved in EB & what do they affect?

Answer 17

10

skin structure & adhesion

Question 18

what is EB aquisita?

Answer 18

a rare autoimmune condition, acquired usually in their 6th/7th decade of life

Question 19

what happens in haploinsufficiency?

Answer 19

only one copy of the gene is working - reduced protein production

Question 20

what happens in dominant negative mutations?

Answer 20

expression of an abnormal protein interferes with normal protein

Question 21

what happens in gain of function mutations?

Answer 21

mutant protein gains a new function, affecting cell processes

Question 22

what happens in complete loss of protein?

Answer 22

autosomal recessive - need 2 faulty copies of the gene to stop production of a protein

Question 23

when do cafe au lait macules occur?

Answer 23

from birth onwards

Question 24

how many cafe au lait macules suggest a genetic disease?

Answer 24

more than 5

Question 25

what are the two main clinical signs in neurofibromatosis type 1?

Answer 25

cafe au lait macules

neurofibromas

Question 26

what are neurofibromas?

Answer 26

soft neural tumours

Question 27

what other features are found in NF type 1?

Answer 27

plexiform neuroma - diffuse
axillary/inguinal freckling 
optic gliomas 
2 or morelisch nodules in the eye 
a distinctive bony lesion

Question 28

when would lish nodules appear in the eye in NF 1?

Answer 28

aged 10+

Question 29

what is the primary abnormality in atopic eczema & what is it determined by?

Answer 29

issue with skin’s barrier function

determined by genetic factors

Question 30

which gene is important in skin barrier function?

Answer 30

filaggrin gene

Question 31

what do filaggrin mutations cause?

Answer 31

ichthyosis vulgaris

Question 32

what triad of symptoms describes eczema?

Answer 32

fine scaling (dryness of the skin)
keratosis pylorus
hyper-linearity

Question 33

which layer of the skin is not present in ichthyosis vulgaris?

Answer 33

no granular layer