Inherited blistering diseases

Question 1

Darier’s disease is inherited in _____ fashion with _____ penetrance and ____ expressivity.

Answer 1

Autosomal Dominant (darier is dominant)

• complete penetrence
• variable expressivity

Question 2

Peak ago of onset in Darier’s disease?

Answer 2

puberty

Question 3

What is the prognosis of Darier’s disease?

Answer 3

• chronic course without remission

Question 4

What is the mutation in Darier’s disease?

Answer 4

• ATP2A2 (which encdoes SERCA2)

Question 5

Darier’s disease mutation is ATP2A2, what is the pathogenesis of the disease with relation to this mutation?

Answer 5

• ATP2A2 encodes SERCA2= calcium ATPase of endoplasmic reticulum–>defective calcium in ER–>impaired synthesis and folding of cell adhesion proteins—> keratinocyte acantholysis and apoptosis

Question 6

What are the primary lesions of Darier’s disease?

Answer 6

• Malodorous, warty, crusted, and red-brown papules/plaques in seborrheic distribution.
• almost always see keratotic palmar papules/pits; longitudinal red and white alternating nail streaks w distal V-shaped notching (50% have oral cobblestoning)

Question 7

What are some classic findings in Darier’s disease (apart from the primary warty crusted red-brown papules/plaques in seborrheic distribution)?

Answer 7

ALMOST ALWAYS: keratotic palmar papules/pits; longitudinal red and white alternating nail streaks w distal V-shaped notching (50% have oral cobblestoning)