Epidermolysis bullosa and congenital skin fragility

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. 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, 2:55 p.m. | Last Modified: 20 May 2026, 2:58 p.m.

Panel Version: 2.15

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, 2:52 p.m. | Last Modified: 20 May 2026, 2:52 p.m.

Panel Version: 2.13

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

Green List (high evidence)

Following discussion with the Genomics England clinical team KRT10 can be classified as Green.

Created: 4 Dec 2019, 10:31 a.m. | Last Modified: 4 Dec 2019, 10:31 a.m.

Panel Version: 0.24

This gene was part of a gene list collated by John McGrath, KCL and Veronica Kinsler, UCL, 17.Jun.2019 on behalf of the GMS Skin Specialist Test Group. Gene Symbol submitted:KRT10; Suggested initial gene rating: Green; Evidence for inclusion: none provided; Evidence for exclusion: none provided; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none provided.

Created: 9 Sep 2019, 3:38 p.m. | Last Modified: 9 Sep 2019, 3:38 p.m.

Panel Version: 0.15

Note from John McGrath (email correspondance): There is an argument to have KRT1, KRT10 and KRT2 as green genes as patients can present with skin fragility initially before the ichthyosis phenotype ensues.

Created: 7 Jan 2019, 4:50 p.m.

Red List (low evidence)

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Epidermolytic hyperkeratosis, 113800; EHK