Ichthyosis, Cyclic, With Epidermolytic Hyperkeratosis

A number sign (#) is used with this entry because the phenotype can be caused by mutation in the keratin 1 gene (KRT1; 139350) or the keratin 10 gene (KRT10; 148080).

Clinical Features

Sybert et al. (1999) described 4 individuals from 2 families with a unique clinical disorder with histologic findings of epidermolytic hyperkeratosis, a hallmark feature of bullous congenital ichthyosiform erythroderma (113800) on light and electron microscopy. Affected individuals manifested erythema and superficial erosions at birth, which improved during the first few months of life; later, palmoplantar hyperkeratosis with patchy erythema and scale developed elsewhere on the body. Three affected individuals exhibited dramatic episodic flares of annular, polycyclic erythematous plaques with scale, which coalesced to involve most of the body surface. The flares lasted weeks to months. In the interim periods the skin was normal except for palmoplantar hyperkeratosis. Abnormal keratin-filament aggregates were observed in suprabasal keratinocytes from both probands.

Joh et al. (1997) reported a family with a similar phenotype, characterized by blistering in childhood accompanying and followed by polycyclic erythematous hyperkeratosis but without palmoplantar involvement. The proband suffered from bullous ichthyosis and had bouts of disease activity associated with the development of numerous annular and polycyclic erythematous, hyperkeratotic plaques on the trunk and the proximal extremities.

Molecular Genetics

In the proband of one family affected with cyclic ichthyosis with epidermolytic hyperkeratosis, Sybert et al. (1999) found a 1436T-C transition mutation in the keratin 1 gene that predicted an amino acid change from isoleucine to threonine at codon 479 (I479T; 139350.0005). This alteration in the highly conserved portion of helix 2B, known as the helix termination motif, created a new BsmAI restriction site. In the second family, Sybert et al. (1999) detected a 1435A-T translation that predicted a substitution of isoleucine-479 by phenylalanine (I479F; 139350.0006). This mutation was carried by the proband, his mother, and his maternal aunt. Both mutations were found in heterozygosity.

A mutation in the 2B helical segment of the KRT10 protein, arg83 to glu (R83E; 148080.0014), caused the phenotype in the family of Joh et al. (1997). KRT10 encodes the partner keratin of KRT1; both are present in suprabasal cells.