Description
Genodermatoses with malignancies eligibility statement:

Genodermatoses with malignancies inclusion criteria (30624)
- proband has clinical features diagnostic or resulting in an operational diagnosis
for Gorlin syndrome or Cowden syndrome OR
- proband has colorectal cancer (diagnosed age <60) AND >= 1 sebaceous adenoma, sebaceous carcinoma or epithelioma (histologically confirmed, diagnosed age <60)

Unaffected individuals should not be recruited in this disorder. Recruitment should favour multiplex families over single isolated cases. These singleton recruits will not contribute to the overall singleton monitoring metrics applied to GMCs.

Genodermatoses with malignancies exclusion criteria (30624)

Prior genetic testing guidance (30624)
- 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.

Genodermatoses with malignancies prior genetic testing genes (30624)
Testing as below is strongly recommended PRIOR TO RECRUITMENT to allow appropriate management of families with readily detectable mutations in known disease genes:

- PTCH1 (Gorlin), PTEN (Cowden), MLH1, MSH2, MSH6 (Muir Torre)

Closing statement (30624)
These requirements will be kept under continual review during the main programme and may be subject to change.

3 reviewers

  • Ajith Kumar (Great Ormond Street Hospital)

    Group: NHS Genomic Medicine Centre
    Workplace: NHS clinical service

  • Ellen Thomas (Genomics England Curator)

    Group: Other
    Workplace: Other

  • Eleanor Williams (Genomics England Curator)

    Group: Other
    Workplace: Other

12 genes

9 reviewed, 6 green

List Gene Reviews Mode of inheritance Details
12 genes
Green Green List (high evidence)
MLH1
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Eligibility statement prior genetic testing
  • UKGTN
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Colorectal cancer, hereditary nonpolyposis, type 2, 609310
  • Mismatch repair cancer syndrome, 276300
  • Muir-Torre syndrome, 158320
  • Muir-Torre Syndrome
Green Green List (high evidence)
MSH2
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Eligibility statement prior genetic testing
  • UKGTN
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Colorectal cancer, hereditary nonpolyposis, type 1, 120435
  • Muir-Torre syndrome, 158320
  • Mismatch repair cancer syndrome, 276300
  • Muir-Torre Syndrome
Green Green List (high evidence)
MSH6
1 review
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Eligibility statement prior genetic testing
Phenotypes
  • Muir-Torre syndrome
Green Green List (high evidence)
PTCH1
1 review
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Eligibility statement prior genetic testing
  • Expert
  • UKGTN
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Basal cell nevus syndrome, 109400
  • Basal cell carcinoma, somatic, 605462
  • Holoprosencephaly-7, 610828
  • Nevoid Basal Cell Carcinoma Syndrome (aka Gorlin syndrome)
  • Basal Cell Nevus Syndrome (aka Gorlin syndrome)
  • Basal cell nevus syndrome
  • Nevoid Basal Cell Carcinoma Syndrome
  • (originally on Gorlin syndrome gene panel)
Green Green List (high evidence)
PTEN
1 review
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Eligibility statement prior genetic testing
  • Expert list
  • UKGTN
  • Emory Genetics Laboratory
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Cowden syndrome 1, 158350
  • Lhermitte-Duclos syndrome, 158350
  • Bannayan-Riley-Ruvalcaba syndrome, 153480
  • {Meningioma}, 607174
  • {Glioma susceptibility 2}, 613028
  • Macrocephaly/autism syndrome, 605309
  • PTEN hamartoma tumor syndrome
  • VATER association with macrocephaly and ventriculomegaly, 276950
  • {Prostate cancer, somatic}, 176807
  • Thyroid carcinoma, follicular, somatic, 188470
  • Malignant melanoma, somatic, 155600
  • Endometrial carcinoma, somatic, 608089
  • Squamous cell carcinoma, head and neck, somatic, 275355
  • Cowden Syndrome
  • Cowden Disease
Green Green List (high evidence)
SUFU
1 review
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
  • Expert Review Green
Phenotypes
  • Medulloblastoma
  • Medulloblastoma, desmoplastic
  • {Meningioma, familial, susceptibility to}
  • (originally on Gorlin syndrome gene panel)
Amber Amber List (moderate evidence)
PTCH2
1 review
Not set
Sources
  • Expert Review Amber
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Medulloblastoma
  • Basal cell carcinoma, somatic
  • (originally on Gorlin syndrome gene panel)
  • Basal cell nevus syndrome 109400
Tags
  • watchlist
Red Red List (low evidence)
AKT1
1 review
Not set
Sources
  • Expert Review Red
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • IGH Breast cancer, somatic, 114480
  • Colorectal cancer, somatic, 114500
  • Ovarian cancer, somatic, 167000
  • {Schizophrenia, susceptibility to}, 181500 (2)
  • Proteus syndrome, somatic, 176920
  • Cowden syndrome 6, 615109
Red Red List (low evidence)
KLLN
1 review
Not set
Sources
  • Expert Review Red
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Cowden syndrome 4, 615107
Red Red List (low evidence)
PIK3CA
0 reviews
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review
Phenotypes
  • One publication showing mutations in Cowden. Await confirmation.
Red Red List (low evidence)
SDHB
0 reviews
Not set
Sources
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Paragangliomas 4, 115310
  • Pheochromocytoma, 171300
  • Paraganglioma and gastric stromal sarcoma, 606864
  • Cowden syndrome 2, 612359
  • Gastrointestinal stromal tumor, 606764
Red Red List (low evidence)
SDHD
0 reviews
Not set
Sources
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Paragangliomas 1, with or without deafness, 168000
  • Pheochromocytoma, 171300
  • Carcinoid tumors, intestinal, 114900
  • Merkel cell carcinoma, somatic
  • Paraganglioma and gastric stromal sarcoma, 606864
  • Cowden syndrome 3, 615106

0 STRs

0 reviewed, 0 green

List STR Reviews Mode of inheritance Details
0 STRss

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