Genetics clinical cases

Question 1

What are the 3 main types of epidermolysis bullosa ?

Answer 1

• Epidermolysis bullosa simplex
• Junctional epidermolysis bullosa
• Dystrophic epidermolysis bullosa

Question 2

Describe the typical presentation of Epidermolysis bullosa simplex

Answer 2

It is a form of epidermolysis bullosa that causes blisters at the site of rubbing. It typically affects the hands and feet.

Question 3

Describe the typical presentation of Junctional epidermolysis bullosa

Answer 3

Characterised by blister formation within the lamina lucida of the basement membrane zone.

Also presents with blisters at the site of friction, especially on the hands and feet, and has variants that can occur in children and adults.

Question 4

Describe the presentation of Dystrophic epidermolysis bullosa

Answer 4

Variant affecting the skin and other organs. “Butterfly children” is the term given to those born with the disease, as their skin is seen to be as delicate and fragile as a butterfly’s wings.

Question 5

What are the general symptoms of epidermolysis bullosa ? (note depending on the type these can range in severity etc)

Answer 5

• Skin that blisters easily
• Blisters inside the mouth
• Blisters on the hands and soles of the feet
• Scarred skin, sometimes with small white spots called milia
• Thickened skin and nails

Question 6

Match the following type of epidermolysis bullosa to the type of mutation/inheritance of it:

• Epidermolysis bullosa simplex
• Junctional epidermolysis bullosa
• Dystrophic epidermolysis bullosa

Autosomal dominant mutation, affecting the keratin genes KRT5 and KRT14.

Autosomal recessive mutation affecting laminin and collagen.

Can be either autosomal dominant or autosomal recessive. Mutation within the human COL7A1 gene encoding the protein type VII collagen

Answer 6

• Epidermolysis bullosa simplex -

Autosomal dominant mutation, affecting the keratin genes KRT5 and KRT14.

• Junctional epidermolysis bullosa - Autosomal recessive mutation affecting laminin and collagen.
• Dystrophic epidermolysis bullosa - Can be either autosomal dominant or autosomal recessive. Mutation within the human COL7A1 gene encoding the protein type VII collagen

Question 7

What sort of mutations increase the risk for developing atopic eczema ?

Answer 7

Mutations in the gene for the production of filaggrin strongly increased the risk for developing atopic dermatitis.

Question 8

What is the function of filaggrin ?

Answer 8

Filaggrin is a protein that plays an important role in the retention of water in the stratum corneum. People who have these mutations often have dry skin. Filaggrin also plays an important role in keeping the skin surface slightly acidic, hence giving it anti-microbial effects. It breaks down into trans-urocanic acid, which keeps the pH low.

Filaggrin mutations cause ichthyosis vulgaris - an inherited skin condition that occurs when your skin doesn’t shed its dead skin cells. This causes dry, dead skin cells to accumulate in patches on the surface of your skin.

Question 9

Appreciate that eczema is a complex trait

Answer 9