Genetic Skin Disorders

Question 1

What is the cause of ichthyosis vulgaris?

Answer 1

A null mutation that reduces fillagrin expression, which alters the epidermal barrier

Question 2

What disease is caused by a null mutation that reduces filaggrin?

Answer 2

Ichthyosis vulgaris

Question 3

What is this?

Answer 3

Ichthyosis vulgaris

Question 4

What are the features of ichthyosis vulgaris?

Answer 4

Scaling (especially on legs), worse in winter, weather dependent, hyperlinear palms, associated with atopic dermatitis and keratosis pilaris

Question 5

What is the mutation associated with X-linked recessive ichthyosis?

Answer 5

ARSC1 deletion that causes cholesterol sulfate accumulation, which inhibits normal degradation of stratum corneum desmosomes (scale is retained)

Question 6

What are the features of x-linked recessive ichthyosis?

Answer 6

Small to large brown scales, generalized scaling with accentuation on neck, abdomen, back, and legs with sparing of palms/soles/central face/flexors

Question 7

What is this?

Answer 7

X-linked recessive ichthyosis

Question 8

What are collodion babies?

Answer 8

Babies born with an autosomal recessive congenital ichthyosis condition, leading to a saran-like membrane that usually sheds in the first month

Question 9

What is the cause of lamellar ichthyosis?

Answer 9

A deficiency in transglutaminase 1, which is required for maturation and shedding of epidermis

Question 10

What is this?

Answer 10

Lamellar ichthyosis

Question 11

What is congenital ichthyosiform erythroderma?

Answer 11

A genetic disease affecting barrier and infalmmatory pathways that leads to predominant erythroderma with finer scaling

Question 12

What is epidermolytic ichthyosis?

Answer 12

An autosomal dominant disorder characterized by superficial blisters at birth followed by progressive warty skin thickening to compensate and protect from blistering

Question 13

What is this?

Answer 13

Epidermolytic Ichthyosis

Question 14

What is mosaic epidermolytic ichthyosis?

Answer 14

A mutation in keratin 1 or 10 in some cells but not all cells that leads to alterations in the scaling process of all offspring cells

Question 15

What is this?

Answer 15

Mosaic epidermolytic ichthyosis

Question 16

What mutations are responsible for epidermolysis bullosa simplex?

Answer 16

Mutations in KRT5 or KRT14 leading to an autosomal dominant blistering disorder with cleavage through basal cells of epidermis

Question 17

What layer of the epidermis is involved in epidermis bullosa simplex?

Answer 17

Basal layer

Question 18

What is this?

Answer 18

Epidermolysis bullosa simplex

Question 19

What is junctional epidermolysis bullosa?

Answer 19

An autosomal recessive condition that causes deeper lesions, generalized blistering, and early demise

Question 20

What is this?

Answer 20

Junctional epidermolysis bullosa

Question 21

What proteins are altered in junctional epidermolysis bullosa?

Answer 21

Hemidesmosomes that bind epidermis to the dermis

Question 22

What is the cause of dystrophic epidermolysis bullosus?

Answer 22

Mutations on collagen 7 that lead to blistering, scarring, and sites of trauma

Question 23

What are the symptoms of dystrophic epidermolysis bullosus?

Answer 23

Blistering and scaring at sites of trauma. Recessive form leads to growth retardation, hypoalbuminemia, anemia, metastatic skin cancer.

Question 24

What mutation causes neurofibromatosis?

Answer 24

A deletion in neurofibromin (a tumor supressor gene) leading to ras activation

Question 25

What are the symptoms of tumors in neurofibromatosis-1?

Answer 25

Multiple cafe-au-lait spots, lisch nodules, optic gliomas, dermal neurofibromas, learning, speech issues

Question 26

What is this?

Answer 26

Optic gliomas from tumors in neurofibromatosis-1

Question 27

What is basal cell nevus syndrome?

Answer 27

An autosomal dominant mutation in patched gene that leads to developmental abnormalities, cysts of jaw/skin, medulloblastomas in young children, basal cell cancers, ovarian tumors

Question 28

What is tuberous sclerosis?

Answer 28

An autosomal dominant mutation in hamartin or tuberin that interact to inhibit mTOR signaling

Question 29

What are the features of tuberous sclerosis?

Answer 29

Early seizures, retardation, cardic rhabdomyomas, brain tumors, renal angiomyolipomas, pulmonary lympangioleiomyomatosis

Question 30

What are potential future treatment options for genetic skin diseases?

Answer 30

Recombinant protein of missing proteins, exon skipping drugs, gene therapy