Familial and multiple pulmonary arteriovenous malformations


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Inclusion criteria

  • 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.

Exclusion criteria

  • 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

– 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.

Prior genetic testing genes

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

These requirements will be kept under continual review during the main programme and may be subject to change.

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