SM 259: Genetic Disease Flashcards Preview

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Flashcards in SM 259: Genetic Disease Deck (29)
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1
Q

What are Ichthyoses?

A

Greek for scaly fish; a group of disorders grouped due to characteristic skin thickening and scaling

2
Q

Why does skin thickening and scaling occur in Ichthyoses?

A

Believed to be a compensatory mechanism to poor epidermal barrier formation

3
Q

What is the most common form of Ichythoses?

A

Ichythyoses Vulgaris

4
Q

How does Ichythyoses Vulgaris present?

A

Scaling on the lower legs, and mild thickening/hyperlinearity of the palms and soles

5
Q

What causes Ichythyoses Vulgaris?

A

A mutation in the gene encodes Filaggrin, leading to a decrease in the Stratum Granulosum of the Epidermis which normally contains Filaggrin granules

6
Q

Why is Ichythyoses Vulgaris “semidominant”?

A

Loss of 1 Fillagrin allele leads to a milder phenotype than if both alleles are effect (which is lethal)

7
Q

What is Recessive X-linked Ichthyosis?

A

A recessive X-linked Ichthyosis that only occurs in males, which effects the enzyme Steroid Sulfatase

8
Q

What enzyme is effected by Recessive X-linked Ichthyosis, and what does this cause?

A

Steroid Sulfatase; leading to an accumulation of Cholesterol Sulfate in the Epidermis and blood

9
Q

What is “collodion baby”?

A

A rare group of Ichthyosis which results in a baby with a shiny cellophan elike membrane due to a Autosomal Recessive conditions

Includes Lamellar Ichthyosis (TGM) and CIE

Eventually resolves and becomes a different Ichthyosis

10
Q

What gene is mutated in the AR Congenital Ichthyosis Lamellar Ichthyosis that causes Collodion baby?

A

Transglutainase 1, an enzyme needed for normal maturation of and shedding of epidermal cells, is lost, leading to large platelike scales and Collodion baby

11
Q

What is Congenital Ichthyosiform Erythroderma?

A

An AR Congenital Ichthyosis due to 10 potential mutations that causes fine scaling

12
Q

What group of Ichthyosis has blisters?

A

Epidermolytic Icthyosis - an Autosomal Dominant condition

13
Q

How does Epidermolytic Ichthyosis present?

A

A superficial blistering disorder at birth that later changes to thickening to compensate for the barrier abnormality

14
Q

What genes are mutated in Epidermolytic Ichthyosis?

A

Keratins 1 and 10, found above the basal areas of the epidermis, may be mutated, leading to blistering

15
Q

Which Keratins are mutated in blistering disorders, and where are they found?

A

Keratins 1 and 10, found in above basal layer of the epidermis, and mutations cause disorders like Epidermolytic Ichthyosis

Keratins 5 and 14, found in the basal layer of the epidermis, cause Epidermolytic Bullosa Simplex

16
Q

Which Keratin is found in palms and soles?

A

Keratin 9

17
Q

How could mutations in Keratin 1 and 10 manifest differently in the palm?

A

Keratin 1 + 9 form pairs in the palm; a mutation in Keratin 10 has only slightly thickened palms, while a mutation in Keratin 1 has severely thickened palms

18
Q

What Keratins are found in the proliferative basal layer of the Epidermis?

A

Keratins 5 and 14 are found in the proliferative basal layer

Keratins 1 and 10 are found above the proliferative basal layer

19
Q

What is Epidermolysis Bulbosa simplex?

A

A Keratinopathy due to mutations in Keratins 5 or 14, which presents with blistering without significant thickening

20
Q

What are Junctional Epidermolysis Bulbosa?

A

An AR group of disorders which result from the absence of Hemidesmosomes, leading to a loss of skin adhesion

Lethal

21
Q

What is Dystrophic EB?

A

A group of EB that results from mutations in Type VII Collagen, leading to mild scarring and blistering if 1 allele is lost and severe glistering as well as growth retardation and SCC if both alleles are lost

22
Q

What are the three tumor syndromes and what causes them?

A

Mutations that activate signaling pathways cause tumor syndromes, including: Neurofibromatosis, Basal Cell Nevus Syndrome, and Tuberous Sclerosis

23
Q

What is Neurofibromatosis?

A

An AD disorder that causes cafe au lait macules and lisch nodules, later leading to dermal neurofibromas and optic gliomas

24
Q

What causes Neurofibromatosis?

A

Mutations in Neurofibromin, a tumor suppressor gene that negatively regulates Ras, leading to loss of tumor suppression - a loss of heterozygosity

25
Q

What is Basal Cell Nevus Syndrome?

A

An AD tumor syndrome due to mutations in patched, which encodes part of the hedgehog signaling pathway that regulates growth, leading to multiple basal cell cancers in early life

26
Q

What is Tuberous Sclerosis?

A

An AD tumor syndrome that results from mutations in Tuberin and Hamartin, negative regulators of mTOR, leading to white patches on skin and seizures in infancy as well as tumors like: brain tumors, renal angiomyolipomas, and cardiac rhabdomyomas

27
Q

What class of drugs can read through genes?

A

Aminoglycosides

28
Q

What techniques can diagnose genetic disorders early?

A

Amniocentesis and Chorionic Villus sampling

29
Q

How can gene editing treat genetic disorders?

A

RNAi to block a broken gene, CRISPR/Cas9 to replace an abnormal gene