Ichthyosis and erythrokeratoderma

Gene: KRT10

Green List (high evidence)

Comment on mode of inheritance: There are more than 3 unrelated individuals with biallelic KRT10 variants and epidermolytic ichthyosis / hyperkeratosis - heterozygous family members were unaffected. Most individuals presented with generalized erythema, erosions, scaling and easily breaking blisters, with improvement later in life (progression to hyperkeratosis). Based on available evidence, the MOI should be updated from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal.

Created: 20 May 2026, 2:58 p.m. | Last Modified: 20 May 2026, 2:58 p.m.

Panel Version: 4.12

PMID: 16505000 Muller et al., 2006
2 sibs with Epidermolytic hyperkeratosis, homozygous for p.Q434X in KRT10. 7 confirmed heterozygous individuals in the family are unaffected. Phenotype: collodion skin and generalised erythroderma at birth, progressive ichthyosis and erosions. Hyperkeratosis most pronounced around big joints.

PMID: 20302579 Covaciu et al., 2010
Proband with lethal epidermolytic ichthyosis (generalized erythema, erosions, scaling and easily breaking blisters that become less frequent later in life while hyperkeratosis increases). Extensive skin erosions and blisters noted at birth. North African consanguineous family. Homozygous for KRT10 c.1155+5G>A splice variant - parents confirmed het.

PMID: 23957016 Gutierrez et al., 2013
4 affected individuals in a large Venezuelan pedigree. Affected family members were homozygous for KRT10 p.Tyr282Ter and presented with generalized erythroderma, blistering, and erosions at birth, which gradually healed and progressed to hyperkeratosis.

PMID: 29277919 Vodo et al., 2018
12yo female patient with epidermolytic ichthyosis and homozygous for KRT10 c.33_34delinsGTAG, predicted to result in p.Tyr11Ter. Similarly affected sister also homozygous, related healthy parents were both het.

PMID: 34273205 Frommherz et al., 2021
2 patients with non-syndromic ichthyosis and pathogenic KRT10 variants:
Case 29, 3yo: biallelic KRT10 mutations, c.867G>A, p.Glu289= (VUS, predicted to disturb the canonical donor splice site and yield p.Glu290Valfs22Ter) and c.1203T>A, p.Cys401Ter; patient demonstrated a self-improving course with pruritus and mild scaling on the neck as the only symptoms at the age of 1 year.
Case 30, 6yo: het for c.466C>T, p.Arg156Cys, only had pruritus.

PMID: 38741524 Frommherz et al., 2025
Case 20 = Case 29 from PMID: 34273205
Case 32 = 21yo female, homozygous for KRT10 p.Lys439Glyfs*3 with intermediate Epidermolytic ichthyosis subtype.

Created: 20 May 2026, 2:57 p.m. | Last Modified: 20 May 2026, 2:57 p.m.

Panel Version: 4.12

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Epidermolytic hyperkeratosis 2B, autosomal recessive, OMIM:620707; Epidermolytic hyperkeratosis 2A, autosomal dominant, OMIM:620150

Publications

• 16505000
• 20302579
• 23957016
• 29277919
• 34273205
• 38741524

Comment on phenotypes: Previous phenotypes:
Epidermolytic hyperkeratosis (EHK), 113800;erythroderma, prominent scale, and palmoplantar keratoderma;ichthyosis with confetti, 609165;Ichthyosis, cyclic, with epidermolytic hyperkeratosis, 607602

Created: 23 Mar 2021, 3:15 p.m. | Last Modified: 23 Mar 2021, 3:15 p.m.

Panel Version: 1.34

Green List (high evidence)

Comment on list classification: Updated rating from Red to Green after discussion with Helen Brittain: although the initial features of EHK are erythema and blistering, hyperkeratosis follows and is specifically listed in relation to the palms and soles. Therefore appropriate to include to capture the broadest differential. Sufficient unrelated cases (>3) to support causation.

Created: 3 Apr 2017, 11:35 a.m.

Sufficient cases to support causation of epidermolytic hyperkeratosis (EHK, MIM:113800).

Created: 23 Mar 2017, 11:01 a.m.

A mother and son with epidermolytic hyperkeratosis (OMIM:113800), Rothnagel et al. (1992, PMID:1380725) demonstrated a T-to-C transition in codon 15 of KRT10, resulting in a serine for leucine substition. Both affected persons showed widespread hyperkeratosis and palmoplantar keratoderma.

Created: 9 Jan 2017, 4:24 p.m.

Choate et al. (2010, PMID:20798280) summarize the clinical features of ichthyosis with confetti (IWC, OMIM: 609165), a very rare, sporadic severe skin disease in which affected subjects are born with erythroderma owing to defective skin barrier function, prominent scale, and palmoplantar keratoderma.

Created: 9 Jan 2017, 4:22 p.m.