Genetics · MU Sofia

33. Monogenic skin diseases: epidermolysis bullosa, ichthyosis

Covers monogenic skin diseases in two groups: epidermolysis bullosa, with its level-of-cleavage classification table of EB simplex, junctional, dystrophic and Kindler forms, then ichthyosis, with a table of vulgaris, X-linked, lamellar, congenital erythroderma and harlequin types. For each it outlines pathophysiology, subtype features, diagnosis and management, including surveillance for squamous cell carcinoma and a comparison table of ichthyosis vulgaris against severe congenital forms.

Inside: 3 sections · 8 labelled pictures · 6 tables · 15 flashcards · 5 min

Topic 33 of 65 in the MU Sofia syllabus for Genetics (Medicine, Year 3). The free AceMed note covers it in 3 sections, about 570 words (5 min of reading), with 15 flashcards.

In this note

  1. Monogenic Skin Diseases: Epidermolysis Bullosa and Ichthyosis
  2. I. EPIDERMOLYSIS BULLOSA (EB)
  3. II. ICHTHYOSIS

Monogenic Skin Diseases: Epidermolysis Bullosa and Ichthyosis

Monogenic skin diseases are inherited disorders caused by mutations in genes encoding structural proteins of the skin, leading to fragility, abnormal keratinization, or defective barrier function.

They primarily affect the epidermis, basement membrane zone, or dermis, resulting in blistering, scaling, or hyperkeratosis.

Two important groups are:

  • Epidermolysis bullosa (EB) – characterized by skin blistering after minimal trauma.
  • Ichthyosis – characterized by generalized scaling and abnormal cornification.

I. EPIDERMOLYSIS BULLOSA (EB)

Epidermolysis bullosa is a group of inherited mechanobullous disorders characterized by formation of blisters and erosions of the skin and mucous membranes following minor mechanical trauma.

The disease results from defects in proteins responsible for adhesion between skin layers.

Structural Basis of Skin Involvement

Normal skin integrity depends on:

  • Keratin cytoskeleton (within basal keratinocytes),
  • Hemidesmosomes (anchor epidermis to basement membrane),
  • Anchoring fibrils (connect basement membrane to dermis).

Mutations in any of these lead to skin separation at specific levels, which determines the EB subtype.

Classification of Epidermolysis Bullosa

Pathophysiology

  1. 1. Gene mutation → defective structural protein involved in skin adhesion.
  2. 2. Mechanical stress causes separation of skin layers at the mutation-specific level.
  3. 3. Fluid accumulates → blister formation.
  4. 4. Repeated injury leads to chronic wounds, scarring, and deformities.
  5. 5. Severe forms show mucosal involvement, malnutrition, and infection risk.

Clinical Features

General Features (all EB types)

  • Blistering after minor trauma or friction.
  • Erosions, crusting, delayed wound healing.
  • Risk of secondary infection and sepsis.

Subtype-Specific Features

1. EB Simplex (EBS)

  • Blisters limited mainly to hands and feet.
  • Usually heal without scarring.
  • Mildest form; normal life expectancy.

2. Junctional EB (JEB)

  • Severe generalized blistering from birth.
  • Involvement of oral mucosa, airway, GI tract.
  • Failure to thrive; high infant mortality in severe forms.

3. Dystrophic EB (DEB)

  • Blisters heal with scarring and milia formation.
  • Fusion of fingers (mitten deformity).
  • Esophageal strictures, anemia.
  • High risk of aggressive squamous cell carcinoma in adulthood (especially AR-DEB).

Diagnosis

  • Skin biopsy with immunofluorescence mapping → localizes level of cleavage.
  • Transmission electron microscopy → ultrastructural defects.
  • Genetic testing → confirms mutation and inheritance type.
  • Prenatal diagnosis possible in affected families.

Management

  • No curative therapy → supportive and preventive care.
  • Protective dressings, infection control.
  • Nutritional support (especially in severe forms).
  • Surgical correction for deformities.
  • Surveillance for skin squamous cell carcinoma in dystrophic EB.
  • Experimental therapies: gene therapy, protein replacement, stem-cell approaches.

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