Genetic Disorders

Question 1

2 autosomal dominant skin disorders

Answer 1

tuberous sclerosis and epidermolysis bullosa

Question 2

pathophysiology of tuberous sclerosis

Answer 2

due to mutation in chromosome 9-TSC1 gene or chromosome 16- TSC2 gene

Question 3

what are other names for TSC 1 and TSC 2 genes

Answer 3

tuberin and hamartin

Question 4

what are the 3 characteristic signs of tuberous sclerosis

Answer 4

mental retardation, epilepsy, cutaneous abnormalities

Question 5

what are some skin signs of tuberous sclerosis

Answer 5

adenoma sebaceum (red papules around nose)
periungual fibroma
shagreen patches (firm flesh coloured plaques on trunk)
ash leaf hyper pigmentation
forehead plaques
cafe-au-lait
pitting of dental enamel

Question 6

tx for tuberous sclerosis

Answer 6

mTOR inhibitors (rapamycin)

Question 7

tuberous sclerosis may be linked to what other disease is there is a TSC 2 and a PKD 1 mutation

Answer 7

polycystic kidney disease

Question 8

what is epidermolysis bullosa

Answer 8

skin fragility autosomal dominant disorder

Question 9

types of EB

Answer 9

simplex, dystrophic, junctional

Question 10

pathophysiology of EB

Answer 10

defective or absent skin proteins causing trauma-induced blistering shortly following birth

Question 11

normally T1 and T2 keratin joins to form a dimer then a tetramer then filaments, in EB this may not occur due to 4 things- name these

Answer 11

haploinsufficiency
dominant -ve disease (mutant protein stops normal protein from working)
gain of function mutation
complete loss of protein

Question 12

s/s of simplex EB?

Answer 12

localised blistering of hands and feet in hot weather

Question 13

deeper blistering and scarring of basement membrane is…

Answer 13

dystrophic EB

Question 14

which is the most severe and what is it

Answer 14

junctional- characterised by split in lamina Lucida of basement membrane- widespread blistering at birth and absence of skin

Question 15

mx of EB?

Answer 15

no clear tx- gene therapy/ bone marrow transplant

Question 16

what are 2 autosomal recessive diseases

Answer 16

cafe-au-lait and leg ulcers

Question 17

what is the diagnostic feature for genetic cafe-au-lait?

Answer 17

> 5 macules

Question 18

aetiology of cafe-au-lait

Answer 18

T1 & T2 neurofibromatosis, tuberous sclerosis, ataxia telangiectasia, Fanconi’s anaemia

Question 19

s/s associated with cafe-au-lait in NF T1

Answer 19

plexiform neuroma, axillary and inguinal freckling, litchi nodes, bony lesions

Question 20

tx for cafe-au lait

Answer 20

MEK inhibitors e.g. refametinib

Question 21

what are leg ulcers

Answer 21

open lesions between knee and ankle that are open for more than 4 weeks

Question 22

epi of leg ulcers

Answer 22

1% of population >70

Question 23

types of leg ulcers

Answer 23

venous- oedema, varicose veins, hemosiderin deposits, lipodermatosclerosis

arterial- punched out painful ulcers higher in leg, hx of claudication, HT, smoking

rheumatic ulcer

necrobiosis lipoidica- diabetes mellitus, spreading erythema over shin that becomes yellow in centre

pyoderma gangrenous- erythematous nodules that become ulcers (with purple margin). associated with IBD, RA, liver disease (PBC)

Question 24

ix for leg ulcers

Answer 24

hx and exam, ABPI, wound swab

Question 25

what are ABPI readings

Answer 25

1=norm
<0.8= vascular disease
>1.5= calcification

Question 26

tx for leg ulcers

Answer 26

compression bandaging and leg elevation (not for arterial ulcers)