Description
Familial and multiple pulmonary arteriovenous malformations inclusion criteria (33497)
•	Multiple PAVMs confirmed by chest x-ray, thoracic CT scan, other cross sectional imaging or angiography
OR   
•	Single PAVM, AND
•	Family history of PAVM in first or second degree relative, AND
•	Clear evidence of an additional phenotype segregating in the family.

Individuals with syndromic disease should be recruited according to standard guidance, typically as trios. Disease status of apparently unaffected participants should be determined according to standard clinical practice to detect cryptic disease.

In other cases, unaffected individuals should not be recruited. Recruitment in such families should favour multiplex families over single isolated cases. These singleton recruits will not contribute to the overall singleton monitoring metrics applied to GMCs.

Familial and multiple pulmonary arteriovenous malformations exclusion criteria (33497)
•	Known disease causing mutation in ENG, ACVRL1, or SMAD4.
•	Single PAVM with no indication of additional genetic phenotypes in family
•	Radiological “PAVM mimics” such as pulmonary artery aneurysms, pulmonary varices,  bronchocoeles or vascular tumours;
•	Positive contrast echocardiographic studies detecting right to left shunting in the absence of radiological evidence of PAVMs.

Prior genetic testing guidance (33497)
- 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.

Familial and multiple pulmonary arteriovenous malformations prior genetic testing genes (33497)
Testing of the following genes should be carried out PRIOR TO RECRUITMENT where this is in line with current local practice: 
 ENG, ACVRL1, and SMAD4

Closing statement (33497)
These requirements will be kept under continual review during the main programme and may be subject to change.

4 reviewers

  • Ellen McDonagh (Genomics England Curator)

    Group: other
    Workplace: other

  • Claire Shovlin (Imperial College London)

    Group: GeCIP domain
    Workplace: NHS clinical service

  • Sarah Leigh (Genomics England Curator)

    Group: Other
    Workplace: Other

  • Louise Daugherty (Genomics England Curator)

    Group: Other
    Workplace: Other

13 genes

13 reviewed, 3 green

List Gene Reviews Mode of inheritance Details
13 genes
Green Green List (high evidence)
ACVRL1
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • UKGTN
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
  • Eligibility statement prior genetic testing
  • Emory Genetics Laboratory
  • Expert Review Green
Phenotypes
  • Telangiectasia, hereditary hemorrhagic, type 2 600376
Green Green List (high evidence)
ENG
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Eligibility statement prior genetic testing
  • Emory Genetics Laboratory
  • Expert Review Green
  • UKGTN
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Telangiectasia, hereditary hemorrhagic, type 1 187300
Green Green List (high evidence)
SMAD4
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Eligibility statement prior genetic testing
  • UKGTN
  • Emory Genetics Laboratory
  • Radboud University Medical Center, Nijmegen
  • UKGTN
  • Emory Genetics Laboratory
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome 175050
Red Red List (low evidence)
ATM
2 reviews
1 red
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Red
  • UKGTN
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Ataxia-telangiectasia, 208900
Red Red List (low evidence)
ATR
2 reviews
1 red
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Red
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Seckel syndrome 1, 210600
  • Cutaneous telangiectasia and cancer syndrome, familial, 614564
Red Red List (low evidence)
FOXF1
2 reviews
1 red
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
  • Expert Review Red
  • UKGTN
Phenotypes
  • Alveolar capillary dysplasia with misalignment of pulmonary veins 265380
Red Red List (low evidence)
GDF2
2 reviews
1 red
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Red
  • UKGTN
  • Radboud University Medical Center, Nijmegen
  • Emory Genetics Laboratory
Phenotypes
  • Telangiectasia, hereditary hemorrhagic, type 5 615506
Red Red List (low evidence)
KRIT1
2 reviews
1 red
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Emory Genetics Laboratory
  • Illumina TruGenome Clinical Sequencing Services
  • Expert Review Red
  • UKGTN
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Cavernous malformations of CNS and retina 116860
  • Cerebral cavernous malformations-1 116860
  • Hyperkeratotic cutaneous capillary-venous malformations associated with cerebral capillary malformations 116860
Red Red List (low evidence)
MRE11
3 reviews
1 red
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Red
  • UKGTN
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Ataxia-telangiectasia-like disorder, 604391
Red Red List (low evidence)
PIK3CA
2 reviews
1 red
Not set
Sources
  • Expert Review Red
  • UKGTN
Phenotypes
  • Congenital Lipomatous Overgrowth, Vascular Malformations, and Epidermal Nevi
  • Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome
Red Red List (low evidence)
RASA1
3 reviews
1 red
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Red
  • Emory Genetics Laboratory
  • Emory Genetics Laboratory
  • Illumina TruGenome Clinical Sequencing Services
Phenotypes
  • Capillary malformation-arteriovenous malformation 608354
Red Red List (low evidence)
SOX18
1 review
1 red
Not set
Sources
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Hypotrichosis-lymphedema-telangiectasia syndrome, 607823
Red Red List (low evidence)
TEK
2 reviews
1 red
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Red
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
Phenotypes
  • Venous malformations, multiple cutaneous and mucosal 600195

0 STRs

0 reviewed, 0 green

List STR Reviews Mode of inheritance Details
0 STRss

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