Palmoplantar keratoderma and erythrokeratodermas (Version 1.31)

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.

Panel Activity

11 reviewers

Tom Cullup (Great Ormond Street Hospital)

Group: NHS Genomic Medicine Centre
Workplace: NHS diagnostic lab
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
Catherine Snow (Genomics England)

Group: Other
Workplace: Other
Zerin Hyder (Genomics England)

Group: Other
Workplace: Other
Arina Puzriakova (Genomics England Curator)

Group: Other
Workplace: Other
Achchuthan Shanmugasundram (Genomics England Curator)

Group: Other
Workplace: Other

46 Entities

46 reviewed, 34 green

List	Entity	Reviews	Mode of inheritance	Details
Filter Entities 46 Entitiess
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 Tags
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) Tags
Green Green List (high evidence)	ALOXE3	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Other Phenotypes Ichthyosis, congenital, autosomal recessive 3, 606545 Nonbullous congenital ichthyosiform erythroderma (NBCIE) Most patients present with collodion membrane at birth and have palmoplantar keratoderma Tags
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 Tags
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, OMIM:173200 Psoriasis 2, OMIM:602723 Keratotic follicular papules, well-demarcated salmon-colored erythematous plaques covered with fine powdery scales interspersed with distinct islands of uninvolved skin, and palmoplantar keratoderma Tags
Green Green List (high evidence)	CAST	3 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes Peeling skin with leukonychia, acral punctate keratoses, cheilitis, and knuckle pads 616295 Tags
Green Green List (high evidence)	CTSC	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Green Phenotypes Papillon-Lefevre syndrome Haim-Munk syndrome Periodontitis 1, juvenile Tags
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 Tags
Green Green List (high evidence)	DSG1	2 reviews 1 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Expert Review Green Other Radboud University Medical Center, Nijmegen Phenotypes Erythroderma, congenital, with palmoplantar keratoderma, hypotrichosis, and hyper IgE, 615508 Keratosis palmoplantaris striata I, AD, 148700 Tags
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 Eligibility statement prior genetic testing Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN UKGTN Phenotypes Cardiomyopathy, dilated, with woolly hair and keratoderma, OMIM:605676 (AR) Dilated cardiomyopathy with woolly hair, keratoderma, and tooth agenesis, OMIM:615821 (AD) Keratosis palmoplantaris striata II, OMIM:612908 (AD) Tags
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) Tags
Green Green List (high evidence)	GJA1	3 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green Other Radboud University Medical Center, Nijmegen Phenotypes Erythrokeratodermia variabilis et progressiva 3, OMIM:617525 Palmoplantar keratoderma with congenital alopecia, OMIM:104100 Oculodentodigital dysplasia, OMIM:164200 Tags
Green Green List (high evidence)	GJB2	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Eligibility statement prior genetic testing Expert Review Green Radboud University Medical Center, Nijmegen 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 Tags
Green Green List (high evidence)	GJB3	2 reviews	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Expert Review Green Other Radboud University Medical Center, Nijmegen Phenotypes Erythrokeratodermia variabilis et progressiva, 133200 Erythrokeratodermia Variabilis Erythrokeratoderma deafness peripheral neuropathy Tags
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, OMIM:617524 Tags
Green Green List (high evidence)	GJB6	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green Other Phenotypes Ectodermal dysplasia 2, Clouston type, 129500 Clouston syndrome palmoplantar hyperkeratosis ECTODERMAL DYSPLASIA, HIDROTIC, AUTOSOMAL DOMINANT Tags
Green Green List (high evidence)	JUP	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Other Phenotypes Naxos disease, OMIM:601214 Palmoplantar keratoderma, keratoderma with woolly hair, generalised skin fragility, epidermolysis bullosa Tags
Green Green List (high evidence)	KDSR	2 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Other Phenotypes Erythrokeratodermia variabilis et progressiva 4, 617526 Tags
Green Green List (high evidence)	KRT1	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Eligibility statement prior genetic testing Expert Review Green Radboud University Medical Center, Nijmegen 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 Tags
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 Tags
Green Green List (high evidence)	KRT14	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green Other 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 Tags
Green Green List (high evidence)	KRT16	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 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) Tags
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 Eligibility statement prior genetic testing Expert Review Green Radboud University Medical Center, Nijmegen UKGTN Phenotypes Pachyonychia congenita 2, OMIM:167210 Steatocystoma multiplex, OMIM:184500 Tags
Green Green List (high evidence)	KRT6A	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 congenital Pachyonychia Congenita, Type 1 Pachyonychia congenita, Jadassohn-Lewandowsky type, 167200 Tags
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) Tags
Green Green List (high evidence)	KRT6C	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Eligibility statement prior genetic testing Expert Review Green Radboud University Medical Center, Nijmegen Phenotypes Palmoplantar keratoderma, nonepidermolytic, focal or diffuse, 615735 Focal keratoderma dystrophic nails Tags
Green Green List (high evidence)	KRT9	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Eligibility statement prior genetic testing Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN 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 Tags
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 Tags
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 Tags
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 Tags
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 Tags
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 Tags
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 Tags
Green Green List (high evidence)	TRPV3	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green Illumina TruGenome Clinical Sequencing Services Other Radboud University Medical Center, Nijmegen Phenotypes Olmsted syndrome, 614594 Palmoplantar Keratoderma, Mutilating, with Periorificial Keratotic Plaques ?Palmoplantar keratoderma, nonepidermolytic, focal 2, 616400 Tags
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 Eligibility statement prior genetic testing Expert Review Red UKGTN Phenotypes Striate keratoderma with woolly hair Cardiomyopathy, dilated, 1I Tags
Red Red List (low evidence)	DSG2	2 reviews 1 red	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Eligibility statement prior genetic testing Expert Review Red UKGTN Phenotypes Striate keratoderma with woolly hair Arrhythmogenic right ventricular dysplasia 10 Cardiomyopathy, dilated, 1BB Tags
Red Red List (low evidence)	ELOVL4	1 review 1 red	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Literature Phenotypes Spinocerebellar ataxia 34 133190 Tags
Red Red List (low evidence)	FAM83G	2 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Radboud University Medical Center, Nijmegen Phenotypes Palmoplantar keratoderma with leukonychia and abundant curly hair Tags
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 Tags
Red Red List (low evidence)	LIPH	2 reviews 1 red	Not set	Sources Emory Genetics Laboratory Expert Review Red Phenotypes Woolly hair/hypotrichosis syndrome Tags
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) Tags
Red Red List (low evidence)	MT-TS1	2 reviews	MITOCHONDRIAL	Sources Other Phenotypes palmoplantar keratoderma with deafness Keratoderma, Palmoplantar, with deafness Tags
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, OMIM:601952 Tags curated-variant-list non-coding-known-pathogenic promoter
Red Red List (low evidence)	SASH1	1 review	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Literature Radboud University Medical Center, Nijmegen Phenotypes ?Cancer, alopecia, pigment dyscrasia, onychodystrophy, and keratoderma, OMIM:618373 Tags
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 Tags

Major version comments

Promoted to Version 1, April 11th 2017: Reviews were assessed, and panel was revised according to expert review and additional curation.

Palmoplantar keratoderma and erythrokeratodermas (Version 1.31)

11 reviewers

46 Entities

46 reviewed, 34 green

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