Genetic Skin Disorders Flashcards
What is the cause of ichthyosis vulgaris?
A null mutation that reduces fillagrin expression, which alters the epidermal barrier
What disease is caused by a null mutation that reduces filaggrin?
Ichthyosis vulgaris
What is this?
Ichthyosis vulgaris
What are the features of ichthyosis vulgaris?
Scaling (especially on legs), worse in winter, weather dependent, hyperlinear palms, associated with atopic dermatitis and keratosis pilaris
What is the mutation associated with X-linked recessive ichthyosis?
ARSC1 deletion that causes cholesterol sulfate accumulation, which inhibits normal degradation of stratum corneum desmosomes (scale is retained)
What are the features of x-linked recessive ichthyosis?
Small to large brown scales, generalized scaling with accentuation on neck, abdomen, back, and legs with sparing of palms/soles/central face/flexors
What is this?
X-linked recessive ichthyosis
What are collodion babies?
Babies born with an autosomal recessive congenital ichthyosis condition, leading to a saran-like membrane that usually sheds in the first month
What is the cause of lamellar ichthyosis?
A deficiency in transglutaminase 1, which is required for maturation and shedding of epidermis
What is this?
Lamellar ichthyosis
What is congenital ichthyosiform erythroderma?
A genetic disease affecting barrier and infalmmatory pathways that leads to predominant erythroderma with finer scaling
What is epidermolytic ichthyosis?
An autosomal dominant disorder characterized by superficial blisters at birth followed by progressive warty skin thickening to compensate and protect from blistering
What is this?
Epidermolytic Ichthyosis
What is mosaic epidermolytic ichthyosis?
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
What is this?
Mosaic epidermolytic ichthyosis
What mutations are responsible for epidermolysis bullosa simplex?
Mutations in KRT5 or KRT14 leading to an autosomal dominant blistering disorder with cleavage through basal cells of epidermis
What layer of the epidermis is involved in epidermis bullosa simplex?
Basal layer
What is this?
Epidermolysis bullosa simplex
What is junctional epidermolysis bullosa?
An autosomal recessive condition that causes deeper lesions, generalized blistering, and early demise
What is this?
Junctional epidermolysis bullosa
What proteins are altered in junctional epidermolysis bullosa?
Hemidesmosomes that bind epidermis to the dermis
What is the cause of dystrophic epidermolysis bullosus?
Mutations on collagen 7 that lead to blistering, scarring, and sites of trauma
What are the symptoms of dystrophic epidermolysis bullosus?
Blistering and scaring at sites of trauma. Recessive form leads to growth retardation, hypoalbuminemia, anemia, metastatic skin cancer.
What mutation causes neurofibromatosis?
A deletion in neurofibromin (a tumor supressor gene) leading to ras activation
What are the symptoms of tumors in neurofibromatosis-1?
Multiple cafe-au-lait spots, lisch nodules, optic gliomas, dermal neurofibromas, learning, speech issues
What is this?
Optic gliomas from tumors in neurofibromatosis-1
What is basal cell nevus syndrome?
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
What is tuberous sclerosis?
An autosomal dominant mutation in hamartin or tuberin that interact to inhibit mTOR signaling
What are the features of tuberous sclerosis?
Early seizures, retardation, cardic rhabdomyomas, brain tumors, renal angiomyolipomas, pulmonary lympangioleiomyomatosis
What are potential future treatment options for genetic skin diseases?
Recombinant protein of missing proteins, exon skipping drugs, gene therapy
