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47 Cards in this Set
- Front
- Back
Name the Major EB Simplex subtypes (4) and the Minor EB Simplex subtypes (3)
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Major:
EBS, Weber-Cockayne EBS, Koebner EBS, Dowling-Meara EBS with muscular dystrophy Minor: EBS with mottled pigmentation AR EBS EBS superficialis |
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Name the Major JEB subtypes (4) and the Minor JEB subtypes (2)
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Major:
JEB, Herlitz JEB, non-Herlitz JEB w/ pyloric atresia EBS with muscular dystrophy* Minor: JEB inversa JEB, localized (mitis) |
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Name the Major DEB subtypes (3) and the Minor DEB subtypes (6)
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AD DEB
AR DEB, Hallopeau-Siemens AR DEB, Non-Hallopeau-Siemens Minor: DDEB, pretibial DDEB, pruriginosa RDEB, inversa RDEB, centripetalis DEB, transient bullous dermolysis of the newborn DEB, autosomal dominant/autosomal recessive heterozygote |
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What is the most common form of EBS? How does it manifest?
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Weber-Cockayne
aka "localized EBS" MN: "Webs & Socks" limited to palms and soles Manifests later in life. May see hyperhidrosis & Hyperkeratosis of palms and soles. |
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Describe the Generalized (Koebner) Variant
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Generalized bulla formation, with heat/friction
Presents AT BIRTH or infancy Improves with age (normal lifespan, just like Weber-Cockayne) Mild Mucosal involvement Nails u/s normal Hyperhidrosis + hyperkeratosis of palms & soles |
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What is the most severe form of EBS?
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Dowling-Meara
aka Herpetiformis |
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How does EBS-Dowling Meara present? Other key clinical findings? EM findings?
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Generalized blisters
Large in the newborn (seen AT BIRTH) increased morbidity & mortality (usu die w/in 1st year) Difficult to tell from dystrophic/junctional EB Herpetiform-like in later infancy or childhood Non-scarring PPK with ↑ age Oro-esophageal erosions Nail involvement (but re-grow) +/- dystrophy Natal teeth Clumped tonofilaments on EM |
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Which form of EBS has EM finding of clumped tonofilaments?
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EBS-Dowling Meara (Herpetiformis)
MN "Drowning in clumps" |
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Where is the keratin defect for EBS Dowling Meara?
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K5 K14 -- The End Terminal rod domains (very critical for keratin function) therefore more severe defect than other EBS (Weber Cockayne)
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Describe EB Simplex superficialis (EBSS)
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Superficial peeling of skin, no overt blistering, unknown defect
Histo: intraepidermal blister just beneath granular layer |
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Name mutation in Naegeli-Franceschetti-Jadassohn syndrome
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KRT14
Absense of dermatoglyphics; reticulate hyperpigmentation of skin; thickening of palms and soles; abnormal sweating |
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Name the mutation in Dowling-Degos disease
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KRT5
Has progressive, disfiguring hyperpigmentation in a reticular pattern on the flexural areas |
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Where is the split in JEBs? Is it present at birth? what about nail and lip involvement?
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Split: Lamina lucida, components of the hemidesmisomes
Erosions present at birth See sloughing of nails & peri-oral involvement with sparing of lips |
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How is JEB inherited?
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AR
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Describe EM and teeth findings in Herlitz type JEB (aka Lethal JEB)
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EM: markedly reduced or absent hemidesmosomes
Enamel hypoplasia characteristic of ALL JEB types Teeth Pitting (“cobblestoning”) Can lead to early caries (also seen in AR DEB) |
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What % of patients with Herlitz type JEB die by 2 yrs old? What about non-Herlitz?
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Herlitz: 50% by age 2y/o die
Non-Herlitz: normal lifespan |
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Generalized blistering, large erosions—buttocks, perioral, trunk, scalp
Peri-oral granulation tissue with sparing of lips Blisters heal with atrophy, but no milia Periungual and fingerpad blistering, erosions nail sloughing/anonychia Oral & laryngeal involvement with hoarseness Dental enamel dysplasia w/ “cobblestoning |
Herlitz type aka Lethal JEB
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What is the mutation in Herlitz type JEB aka Lethal JEB?
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AR
Pathophysiology: Premature termination codon or non-sense mutation within any of the 3 protein subunits of laminin-5 (on chromo 1q32) LAMA3 (laminin α3-chain), LAMB3 (laminin β3-chain), LAMC2 (laminin γ2-chain) |
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Defect in:
LAMA3 (laminin α3-chain), LAMB3 (laminin β3-chain), LAMC2 (laminin γ2-chain) |
Herlitz type JEB (aka Lethal JEB)
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What is the mutation in Non-Herlitz / GABEB?
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AR with defects in laminin 5 or BP Ag2 (aka “BP 180” or “collagen type XVII ”)
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What chromosome is Laminin 5 on? BPAg2?
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Laminin-5 genes on chromo 1q32 S2 Herlitz
BPAg2 --> COL17A1 gene on chromo 10q24 |
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Bullae that heal with atrophic scars
Nail dystrophy & scarring alopecia Generally with a normal lifespan ↓ blisters with time |
Non-Herlitz / GABEB
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Defect in JEB w/ Pyloric Atresia
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Defect: a6B4 integrin gene
a6 integrin --> ITG-A6 gene on chromosome 2 B4 integrin --> ITG-B4 gene on chromosome 17q11 |
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More common in males (♂ > ♀)
Skin findings are S2 Herlitz variant Defining characteristics: Pyloric atresia GU abnormalities: strictures of urethra or ureters, hydronephrosis, renal failure |
JEB with Pyloric Atresia
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EBS with Muscular Dystrophy
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EBS with Muscular Dystrophy Inheritance? Defect?
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AR
Plectin gene (500 kd) MN – PHAT, PLAKIN, PHYSICALLY DISABLED Plectin is found in both hemidesmosomes & skeletal muscles |
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Mild blistering
Mild nail dystrophy No dental anomalies |
EBS with Muscular Dystrophy
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JEB:
Mild blistering No mucosal involvement Almost always dental enamel hypoplasia |
JEB - Mitis variant
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JEB with
Blisters/erosions on skin folds |
JEB - Inverse form
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Defect in Dystrophic EB?
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Collagen VII defect due to COL7A1 gene on chromo 3p21
Same gene for both AD & AR DEB |
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This type of EB can also have:
Eye --> blindness Esophagus --> strictures Small intestine --> malabsorption, anemia, vitamin & nutritional deficiencies Large intestine --> constipation, strictures GU tract --> strictures, obstruction |
Dystrophic EB (more likely than EBS and JEB to have extracutaneous)
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Onset at birth to early infancy
Blistering predominates on extensor surfaces of extremities (dorsum of hands, elbows, knees, and lower legs) Milia associated with scarring 80% have nail dystrophy Less severe, generally healthy, normal stature |
Dominant dystrophic DEB
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The Pathophysiology of this EB is: Glycine mutations (glycosylation sites) --> defective triple helix assembly
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Dominant Dystrophic DEB
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What are the two variants of AD Dystrophic EB?
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Albopapuloid Pasini Variant
Cockayne-Touraine (Hyperplastic) Variant |
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More widespread distribution
Albopapuloid lesions --> Hypopigmented scar-like papules on trunk + Mucosa & teeth involvement |
Albopapuloid Pasini Variant of AD Dystrophic EB
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Limited acral distribution --> Extremity bullae heal with scarring +/- hyperplastic
NO albopapuloid lesions NO mucosal or teeth involvement |
Cockayne-Touraine (hyperplastic) Variant
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Extensive blistering at birth
Dramatic improvement in 1st few months of life Blistering u/s ends by age 2 y/o Mild atrophy/scarring No other abnormalities Defect: Type VII collagen Thought to be caused by delay in transfer of Collagen VII from basal keratinocytes to underlying ECM |
Transient Bullous Dermolysis of the Newborn (Transient EB)
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Defect for Transient Bullous Dermolysis of the Newborn
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Type VII Collagen
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What is pseudosyndactyly?
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Mitten deformities of hands and feet -- seen in Recessive Dystrophic (Hallopaeu-Siemens)
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What skin cancer are pt's with recessive dystrophic EB (hallopeau-siemens are risk for)?
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SCC (40% of pts by age 30)
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What is the pathophysiology of recessive dystrophic EB (hallopaeu-siemens)?
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Type VII Collagen:
Pathophysiology: Stop codon mutation --> NO fibrils |
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Describe AR DEB - Non-Hallopeau-Siemens
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Can have all the findings of AR DEB, but less severe
Bullae mainly on acral bony prominences--> can look very S2 AD DEB Fragility improves w/ age |
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What is the pathophysiology of AR DEB, non-Hallopeau-Siemens?
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Pathophysiology: Missence or frameshift mutation in collagen 7 gene --> defective anchoring fibrils
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Compare the life span of the different types of DEB?
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AD DEB : Normal
AR DEB: Hallopeau-Siemens Death within 1st 3 decades of life AR DEB: Non-Hallopeau-Siemens (variable, if mild then normal lifespan) |
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What is BART Syndrome?
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Localized congenital absence of skin (aplasia cutis)
Phenotypic pattern seen in EB pts M/C occurs in DEB pts (either AD or AR), but can occur in any EB type DDx: Other disorders with congenital localized absence of skin – eg. aplasia cutis congenita But these d/o’s do NOT have blisters present |
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Ectodermal Dysplasia w/ skin fragility:
Inheritance & gene defect Clinical Picture |
AR
Plakophilin-1 gene defect (desmosomal component) At birth, generalized erythroderma with blistering Improves with age Trauma-induced skin fragility Soles are the worst PPK w/ painful fissuring Ectodermal dysplasia Short, sparse hair Thick, dystrophic nails Hypo-hidrosis |
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Kindler Syndrome
Defect? Clinical picture? |
KIND-1 gene defect
-- Encodes a protein linking actin with the extracellular matrix Generalized progressive poikiloderma – worsens w/ age Atrophic scarring – worsens w/ age Congenital acral skin blistering – blister formation improves w/ age Photosensitivity – improves w/ age Diffuse cutaneous atrophy – increased with age Skin fragility Webbing of fingers/toes Nail dystrophy Oral mucosal lesions Others -- PPK, leukokeratosis -- red friable gums, GU/GI stenosis |