Description
Eligibility statement for Palmoplantar keratoderma and erythrokeratodermas (33701):

Palmoplantar keratoderma and erythrokeratodermas inclusion criteria (33465)
Diagnosis of one of the following confirmed by consultant dermatologist:
•	Diffuse palmoplantar keratoderma 
•	Focal keratoderma with or without nail involvement
•	Pachyonychia congenita phenotype (focal keratoderma with pain and dystrophic nails, oral leukokeratosis and or follicular hyperkeratoses/cysts).  
•	Punctate keratoderma
•	Striate keratoderma alone
•	Striate keratoderma with woolly hair
•	Keratoderma with deafness
•	Unusual/unique rare keratodermas occuring alone or as part of syndromes.
•	Erythrokeratoderma

Palmoplantar keratoderma and erythrokeratodermas exclusion criteria (33465)

Prior genetic testing guidance (33465)
- Results should have been reviewed for all genetic tests undertaken, including disease-relevant genes in exome sequencing data. The patient is not eligible if they have a molecular diagnosis for their condition. 
- Genetic testing should continue according to routine local practice for this phenotype regardless of recruitment to the project; results of these tests must be submitted via the ‘Genetic investigations’ section of the data capture tool to allow comparison of WGS with current standard testing.  

PLEASE NOTE: The sensitivity of WGS compared to current diagnostic genetic testing has not yet been established. It is therefore important that tests which are clinically indicated under local standard practice continue to be carried out.

Palmoplantar keratoderma and erythrokeratodermas prior genetic testing genes (33465)
Testing of the following genes should be carried out PRIOR TO RECRUITMENT where this is in line with current local practice: 
 -	Diffuse palmoplantar keratoderma: KRT9 and KRT1 
-	Focal keratoderma: KRT16 and KRT6C 
-	Pachyonychia congenital: KRT6A, KRT6B, KRT6C, KRT16 and KRT17 
-	Striate keratoderma: KRT1 and KRT16 
-       Striate keratoderma with woolly hair: cardiac panel including desmosomal genes 
-       Keratoderma with deafness: GJB2

Closing statement (33465)
These requirements will be kept under continual review during the main programme and may be subject to change.

6 reviewers

  • Edel O'Toole (Queen Mary University of London)

    Group: GeCIP domain
    Workplace: NHS clinical service

  • Veronica Kinsler (UCL)

    Group: GeCIP domain
    Workplace: Research lab

  • Ellen Thomas (Genomics England Curator)

    Group: Other
    Workplace: Other

  • Sarah Leigh (Genomics England Curator)

    Group: Other
    Workplace: Other

  • Rebecca Foulger (Genomics England curator)

    Group: Other
    Workplace: Other

  • Helen Brittain (Genomics England Curator)

    Group: Other
    Workplace: Other

45 genes

45 reviewed, 33 green

List Gene Reviews Mode of inheritance Details
45 genes
Green Green List (high evidence)
AAGAB
3 reviews
2 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Keratoderma, palmoplantar, punctate type IA, 148600
  • Punctate keratoderma
  • Punctate keratoderma and congenital dysplasia of the hip
  • PPKP Buschke-Fischer-Brauer type
Green Green List (high evidence)
ALOX12B
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Other
Phenotypes
  • Ichthyosis, congenital, autosomal recessive 2, 242100 (includes palmoplantar keratoderma)
  • Nonbullous congenital ichthyosiform erythroderma (NBCIE)
Green Green List (high evidence)
ALOXE3
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Other
  • Expert Review Green
Phenotypes
  • Ichthyosis, congenital, autosomal recessive 3, 606545
  • Nonbullous congenital ichthyosiform erythroderma (NBCIE)
  • Most patients present with collodion membrane at birth and have palmoplantar keratoderma
Green Green List (high evidence)
AQP5
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Palmoplantar keratoderma, Bothnian type, 600231
Green Green List (high evidence)
CARD14
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Other
Phenotypes
  • Pityriasis rubra pilaris, 173200
  • familial pityriasis rubra pilaris
  • keratotic follicular papules, well-demarcated salmon-colored erythematous plaques covered with fine powdery scales interspersed with distinct islands of uninvolved skin, and palmoplantar keratoderma
Green Green List (high evidence)
CAST
3 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
Phenotypes
  • Peeling skin with leukonychia, acral punctate keratoses, cheilitis, and knuckle pads 616295
Green Green List (high evidence)
DSC2
3 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Eligibility statement prior genetic testing
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • UKGTN
  • UKGTN
Phenotypes
  • Striate keratoderma with woolly hair
  • Arrhythmogenic right ventricular dysplasia 11, 610476
  • Arrhythmogenic right ventricular dysplasia 11 with mild palmoplantar keratoderma and woolly hair, 610476
Green Green List (high evidence)
DSG1
2 reviews
1 green
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • Other
Phenotypes
  • Erythroderma, congenital, with palmoplantar keratoderma, hypotrichosis, and hyper IgE, 615508
  • Keratosis palmoplantaris striata I, AD, 148700
Green Green List (high evidence)
DSP
2 reviews
1 green
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • UKGTN
  • UKGTN
  • Eligibility statement prior genetic testing
Phenotypes
  • Striate keratoderma with woolly hair and cardiomyopathy
  • Keratosis palmoplantaris striata II, 612908
  • CARVAJAL SYNDROME
  • Dilated cardiomyopathy with woolly hair and keratoderma, 605676
  • Arrhythmogenic right ventricular dysplasia 8, 607450
  • Skin fragility-woolly hair syndrome, 607655
  • Epidermolysis bullosa, lethal acantholytic
  • Keratosis palmoplantaris striata II
  • Skin fragility-woolly hair syndrome
  • striate keratoderma
  • diffuse keratoderma
  • lethal acantholytic epidermolysis bullosa, 609638
  • alopecia, follicular hyperkeratoses and keratoderma
  • oligodontia or hypodontia
Green Green List (high evidence)
ENPP1
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Other
Phenotypes
  • Cole disease, 615522 (includes punctate palmoplantar keratoderma)
Green Green List (high evidence)
GJA1
2 reviews
1 green
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Other
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Palmoplantar keratoderma with congenital alopecia, 104100
  • Erythrokeratodermia variabilis et progressiva 3, 617525
  • Erythrokeratoderma
  • Palmoplantar keratoderma
  • Oculodentodigital dysplasia (ODDD) with palmoplantar keratoderma
  • keratoderma, hypotrichosis and leukonychia
Green Green List (high evidence)
GJB2
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • Eligibility statement prior genetic testing
Phenotypes
  • Keratoderma with deafness
  • Deafness, autosomal recessive 1A, 220290
  • Deafness, autosomal dominant 3A, 601544
  • Vohwinkel syndrome, 124500
  • Keratoderma, palmoplantar, with deafness, 148350
  • Keratitis-ichthyosis-deafness syndrome, 148210
  • Hystrix-like ichthyosis with deafness, 602540
  • Bart-Pumphrey syndrome, 149200
Green Green List (high evidence)
GJB3
2 reviews
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • Other
Phenotypes
  • Erythrokeratodermia variabilis et progressiva, 133200
  • Erythrokeratodermia Variabilis
  • Erythrokeratoderma
  • deafness
  • peripheral neuropathy
Green Green List (high evidence)
GJB4
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Erythrokeratodermia variabilis et progressiva 2, 617524
Green Green List (high evidence)
GJB6
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Other
  • Expert Review Green
Phenotypes
  • Ectodermal dysplasia 2, Clouston type, 129500
  • Clouston syndrome
  • palmoplantar hyperkeratosis
  • ECTODERMAL DYSPLASIA, HIDROTIC, AUTOSOMAL DOMINANT
Green Green List (high evidence)
JUP
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Other
Phenotypes
  • Naxos disease, 601214
  • palmoplantar keratoderma (PPK), keratoderma with woolly hair
  • KERATOSIS PALMOPLANTARIS WITH ARRHYTHMOGENIC CARDIOMYOPATHY
  • WOOLLY HAIR, PALMOPLANTAR KERATODERMA, AND CARDIAC ABNORMALITIES
  • PALMOPLANTAR KERATODERMA WITH ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY AND WOOLLY HAIR
Green Green List (high evidence)
KDSR
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Other
Phenotypes
  • Erythrokeratodermia variabilis et progressiva 4, 617526
Green Green List (high evidence)
KRT1
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • Eligibility statement prior genetic testing
Phenotypes
  • Diffuse palmoplantar keratoderma
  • triate keratoderma
  • Epidermolytic hyperkeratosis, 113800
  • Ichthyosis, cyclic, with epidermolytic hyperkeratosis, 607602
  • Ichthyosis histrix, Curth-Macklin type, 146590
  • Palmoplantar keratoderma, nonepidermolytic, 600962
  • Palmoplantar keratoderma, epidermolytic, 1
  • Ichthyosis, cyclic, with epidermolytic hyperkeratosis, 607602
  • Palmoplantar keratoderma, epidermolytic, 1
Green Green List (high evidence)
KRT10
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Other
Phenotypes
  • ichthyosis with confetti, 609165
  • erythroderma, prominent scale, and palmoplantar keratoderma
  • Epidermolytic hyperkeratosis (EHK), 113800
  • Ichthyosis, cyclic, with epidermolytic hyperkeratosis, 607602
Green Green List (high evidence)
KRT14
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Other
  • Expert Review Green
Phenotypes
  • Naegeli-Franceschetti-Jadassohn syndrome, 161000
  • Naegeli-Franceschetti-Jadassohn syndrome/dermatopathia pigmentosa reticularis (NFJS/DPR)
  • palmoplantar keratoderma
  • Dermatopathia pigmentosa reticularis, 125595
  • Epidermolysis bullosa simplex, Dowling-Meara type, 131760
Green Green List (high evidence)
KRT16
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • UKGTN
  • Radboud University Medical Center, Nijmegen
  • Eligibility statement prior genetic testing
Phenotypes
  • Focal keratoderma
  • Pachyonychia congenita, Jadassohn-Lewandowsky type, 167200
  • Palmoplantar keratoderma, nonepidermolytic, focal, 613000
  • Pachyonychia Congenita, Type 1
  • focal non-epidermolytic palmoplantar keratoderma (NEPPK)
  • FNEPPK1
  • striate keratoderma (palmar)
  • focal keratoderma (palmar)
  • Pachyonychia congenita (PC)
Green Green List (high evidence)
KRT17
2 reviews
1 green
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • UKGTN
  • Eligibility statement prior genetic testing
Phenotypes
  • Pachyonychia Congenita, Type 2
  • Pachyonychia congenita, Jackson-Lawler type, 167210
  • Steatocystoma multiplex, 184500
Green Green List (high evidence)
KRT6A
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • UKGTN
  • Eligibility statement prior genetic testing
Phenotypes
  • Pachyonychia congenital
  • Pachyonychia Congenita, Type 1
  • Pachyonychia congenita, Jadassohn-Lewandowsky type, 167200
Green Green List (high evidence)
KRT6B
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Eligibility statement prior genetic testing
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Pachyonychia congenita 4, 615728
  • PC4
  • pachyonychia congenita type 2 (PC-2)
Green Green List (high evidence)
KRT6C
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • Eligibility statement prior genetic testing
Phenotypes
  • Palmoplantar keratoderma, nonepidermolytic, focal or diffuse, 615735
  • Focal keratoderma
  • dystrophic nails
Green Green List (high evidence)
KRT9
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • UKGTN
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • Eligibility statement prior genetic testing
  • Expert Review Green
Phenotypes
  • Palmoplantar keratoderma, epidermolytic, 144200
  • Epidermolytic Palmoplantar Keratoderma (EPPK)
  • Palmoplantar Keratoderma, Epidermolytic
  • Diffuse keratoderma
  • Diffuse keratoderma with knuckle pads
  • Diffuse keratoderma with digital mutilation
  • Vörner type palmoplantar keratoderma
Green Green List (high evidence)
RHBDF2
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Other
Phenotypes
  • tylosis with esophageal cancer, 148500
  • KERATOSIS PALMARIS ET PLANTARIS WITH ESOPHAGEAL CANCER
  • PALMOPLANTAR KERATODERMA WITH ESOPHAGEAL CANCER
  • Hyperkeratosis, diffuse palmoplantar (tylosis)
  • Howel-Evans syndrome
  • Focal keratoderma
  • tylosis with oesophageal cancer
  • oral leukokeratosis
Green Green List (high evidence)
RSPO1
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Palmoplantar hyperkeratosis and true hermaphroditism, 610644
  • Palmoplantar hyperkeratosis with squamous cell carcinoma of skin and sex reversal, 610644
  • palmoplantar keratoderma
Green Green List (high evidence)
SERPINB7
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Palmoplantar keratoderma, Nagashima type, 615598
  • palmoplantar keratoderma, recurrent tinea
Green Green List (high evidence)
SLURP1
2 reviews
1 green
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Other
Phenotypes
  • Meleda disease, 248300
  • Mal de Meleda (MDM)
  • keratosis palmoplantaris transgrediens
  • palmoplantar keratoderma
  • Diffuse palmoplantar keratoderma
Green Green List (high evidence)
SNAP29
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma, 609528
  • CEDNIK syndrome
  • Cerebral Dysgenesis, Neuropathy, Ichthyosis, and Palmoplantar Keratoderma Syndrome
Green Green List (high evidence)
TAT
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Other
Phenotypes
  • Tyrosinemia, type II, 276600
  • KERATOSIS PALMOPLANTARIS WITH CORNEAL DYSTROPHY
  • palmoplantar hyperkeratosis
Green Green List (high evidence)
TRPV3
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
  • Expert Review Green
  • Other
Phenotypes
  • Olmsted syndrome, 614594
  • Palmoplantar Keratoderma, Mutilating, with Periorificial Keratotic Plaques
  • ?Palmoplantar keratoderma, nonepidermolytic, focal 2, 616400
Amber Amber List (moderate evidence)
SMARCAD1
1 review
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Amber
  • Other
Phenotypes
  • Basan syndrome, 129200
  • palmoplantar keratoderma
Tags
  • watchlist
Red Red List (low evidence)
DES
2 reviews
1 red
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Red
  • UKGTN
  • Eligibility statement prior genetic testing
Phenotypes
  • Striate keratoderma with woolly hair
  • Cardiomyopathy, dilated, 1I
Red Red List (low evidence)
DSG2
2 reviews
1 red
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Red
  • UKGTN
  • Eligibility statement prior genetic testing
Phenotypes
  • Striate keratoderma with woolly hair
  • Arrhythmogenic right ventricular dysplasia 10 Cardiomyopathy, dilated, 1BB
Red Red List (low evidence)
ELOVL4
1 review
1 red
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Literature
Phenotypes
  • Spinocerebellar ataxia 34 133190
Red Red List (low evidence)
FAM83G
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Red
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Palmoplantar keratoderma with leukonychia and abundant curly hair
Red Red List (low evidence)
KANK2
2 reviews
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Red
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • PPKWH
  • Palmoplantar keratoderma and woolly hair, 616099
Red Red List (low evidence)
LIPH
2 reviews
1 red
Not set
Sources
  • Expert Review Red
  • Emory Genetics Laboratory
Phenotypes
  • Woolly hair/hypotrichosis syndrome
Red Red List (low evidence)
MBTPS2
1 review
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Sources
  • Literature
Phenotypes
  • IFAP syndrome. 308205, along with pachyonychia, palmoplantar and periorificial keratoderma
  • ?Olmsted syndrome, X-linked, 300918
  • X-linked mutilating palmoplantar keratoderma with periorificial keratotic plaques (Olmsted syndrome)
Red Red List (low evidence)
MT-TS1
2 reviews
MITOCHONDRIAL
Sources
  • Other
Phenotypes
  • palmoplantar keratoderma with deafness
  • Keratoderma, Palmoplantar, with deafness
Red Red List (low evidence)
POMP
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Red
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Keratosis linearis with ichthyosis congenita and sclerosing keratoderma, 601952
Tags
  • non-coding-known-pathogenic
  • curated-variant-list
  • promoter
Red Red List (low evidence)
SASH1
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Radboud University Medical Center, Nijmegen
  • Literature
  • Expert Review Red
Phenotypes
  • Pigmentation defects, palmoplantar keratoderma and skin carcinoma
Red Red List (low evidence)
SDR9C7
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Literature
Phenotypes
  • Autosomal Recessive Congenital Ichthyosis (includes palmoplantar keratoderma)
  • ARCI
  • Ichthyosis, congenital, autosomal recessive 13 617574

0 STRs

0 reviewed, 0 green

List STR Reviews Mode of inheritance Details
0 STRss

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