| • | retention hyperkeratosis; defect in profilaggrin synthesis (?) |
| • | histidine --> profilaggrin --> filaggrin |
| • | a histidine rich basic protein stored as profilaggrin in keratohyaline granules |
| • | responsible for keratin filament aggregation (i.e. the material between keratin filaments) |
| • | name: fil-ament aggr-egating prote-in |
|
| • | the corneocyte has a highly insoluble cornified envelope its formation represents an expression of terminal differentiation of the keratinocyte within the plasma membrane, formed by the cross-linking of the soluble protein precursor involucrin (Greek = envelope) |
| • | envelope precursors (e.g. involucrin, loricrin) are synthesized late in stratification and then cross-linked by the action of transglutaminase enzymes, which are synthesized in the granular layer |
| • | major cell envelope constituents = involucrin, filaggrin and loricrin |
| • | defect in ichthyosis vulgaris – filaggrin |
| • | defect in Vohlwinkel’s syndrome – loricrin |
| • | defect in lamellar ichthyosis - transglutaminase |
|
clinical:
| ◆ | atopic dermatitis (>50%) |
| ◆ | hyperlinear palms (helps differentiate from X-linked) |
| • | onset in early childhood, improves with age |
ddx:
| • | atopic dermatitis, xerosis, X-linked ichthyosis, acquired ichthyosis |
histology:
| ◆ | absent granular layer (makes sense given the primary defect) |
|
