Genetic Skin Conditions

Question 1

What may be seen on the nails of an individual with tuberous sclerosis?

Answer 1

Periungual fibromata and ridging

Question 2

A history of what disease in childhood may be present in tuberous sclerosis?

Answer 2

Epilepsy

Question 3

What may cause seizures in TS?

Answer 3

Cortical tubers and or calcification of the faux cerebri

Question 4

What is the earliest clinical sign of TS? What are these?

Answer 4

Ash-leaf macules (depigmented macule seen in 90% of cases)

Question 5

What may be used to see an ash-leaf macule more clearly?

Answer 5

Wood’s lamp

Question 6

What are 2 features of TS which are associated with increased connective tissue in the skin?

Answer 6

Shagreen patches (redness and lumps) and enamel pitting

Question 7

What are some tumours which TS can cause?

Answer 7

Periungual fibromas, facial angiofibromas, hamartomas, bone cysts, cortical tubers

Question 8

What are facial angiofibromas?

Answer 8

Red lumps on the face which become more prominent in teenage years

Question 9

What makes facial angiofibroma different from acne?

Answer 9

No pustules

Question 10

What are hamartomas?

Answer 10

An overgrowth of normal tissue which is not malignant, usually angiomyolipomas of the heart, lung or kidneys

Question 11

What are cortical tubers? What do they cause?

Answer 11

A type of brain tumour found in 90% of cases which causes epilepsy and varying degrees of mental impairment

Question 12

Within which lobe of the brain are cortical tubers most likely to be found?

Answer 12

Frontal lobe

Question 13

How is TS inherited?

Answer 13

Autosomal dominant, though new mutations are also common

Question 14

What are the two chromosomes that can be associated with TS?

Answer 14

TSC1 and TSC2

Question 15

What do TSC1 and TSC2 code for?

Answer 15

Tuberin (chromosome 9) and hamartin (chromosome 16)

Question 16

What is the function of the genes on chromosomes 9 and 16 involved in TS?

Answer 16

Tumour regulating genes

Question 17

When taking a family history for TS, what sort of things should you look for?

Answer 17

History of seizures, learning difficulties and spots on the skin

Question 18

What increases the risk of new mutations forming?

Answer 18

Increasing age of the father

Question 19

In what generations is an autosomal dominant disease seen?

Answer 19

All generations

Question 20

What is the sex distribution of an autosomal dominant disease?

Answer 20

Equal

Question 21

TS shows genetic heterogeneity, what does this mean?

Answer 21

The mutation can be in one of two genes

Question 22

What is the penetrance of TS? Is it common?

Answer 22

Variable but usually high penetrance, rare disorder

Question 23

How can epidermolysis bullosa be inherited?

Answer 23

Autosomal dominant, recessive or there can be new mutations

Question 24

Does blistering at birth determine the prognosis of EB?

Answer 24

No

Question 25

What is epidermolysis bullosa known as when the split is at the a) epidermis? b) DE junction? c) dermis?

Answer 25

a) simplex, b) junctional, c) dystrophic

Question 26

Where is the split in normal blisters?

Answer 26

DE junction

Question 27

Damage to which part of the skin will always cause scarring?

Answer 27

Dermis

Question 28

What genes are involved in epidermolysis bullosa?

Answer 28

There are over 10 genes involved, all related to skin structure and adhesion

Question 29

What is epidermolysis bullosa aquisita?

Answer 29

A rare autoimmune condition

Question 30

Is any protein produced in an autosomal recessive disease? What is this known as?

Answer 30

No (because both genes are mutant), this is known as complete loss of function

Question 31

What is haploinsufficiency?

Answer 31

Only one copy of the gene is working so there is reduced protein production

Question 32

What is dominant negative?

Answer 32

Expression of the abnormal protein interferes with the normal protein

Question 33

Where can mutations come from?

Answer 33

A parent having the mutation, de-novo, mosaic parent

Question 34

What genetic test can be used to work out if an individual is a genetic mosaic?

Answer 34

Next generation sequencing

Question 35

How many generations are generally affected by autosomal recessive diseases?

Answer 35

Usually only 1

Question 36

There is increased likelihood of autosomal recessive disorders when?

Answer 36

Parents are related

Question 37

What skin symptoms can be seen in neurofibromatosis type 1?

Answer 37

Cafe au lait macules, neurofibromas, axillary/inguinal freckling

Question 38

How many cafe au last macules suggest genetic disease?

Answer 38

> 5

Question 39

What are neurofibromas?

Answer 39

Soft neural tumours

Question 40

Apart from the skin symptoms, what else can be seen in NF1?

Answer 40

Optic glioma, bony lesions