KRT10 – Annular Epidermolytic Ichthyosis

Annular epidermolytic ichthyosis is a rare autosomal dominant variant of bullous congenital ichthyosiform erythroderma characterized by recurrent annular and polycyclic erythematous hyperkeratotic plaques and blistering. Two unrelated pedigrees have been reported: a multigenerational family with two affected generations showing perinuclear tonofilament clumping on electron microscopy and a second pedigree with intrafamilial phenotypic heterogeneity presenting as annular, localized or generalized epidermolytic ichthyosis, both harboring heterozygous missense variants in KRT10, consistent with dominant inheritance (PMID:9036939, PMID:26338057).

Molecular analysis identified a novel tandem CG→GA dinucleotide mutation in one family and a c.457C>A (p.Leu153Met) substitution in another, both affecting conserved residues in the 1A rod domain of keratin 10 and leading to disrupted filament assembly on ultrastructural examination (PMID:9036939). These findings support a dominant-negative mechanism. Annular epidermolytic ichthyosis should be considered within the spectrum of KRT10-related epidermolytic keratinization disorders.

Key take-home: Heterozygous KRT10 missense variants cause autosomal dominant annular epidermolytic ichthyosis, with diagnostic utility in targeted genetic testing and implications for genetic counselling.

References

• The Journal of investigative dermatology • 1997 • A novel dinucleotide mutation in keratin 10 in the annular epidermolytic ichthyosis variant of bullous congenital ichthyosiform erythroderma. PMID:9036939
• Clinical and experimental dermatology • 2016 • Intrafamilial phenotypic heterogeneity of epidermolytic ichthyosis associated with a new missense mutation in keratin 10. PMID:26338057

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