Thoracic aortic aneurysm or dissection (GMS)

Gene: FLCN

Red List (low evidence)

Submitted on behalf of the GMS Cardiology specialist group. The group has agreed that this gene should be Red on this panel. Therefore this gene has been demoted from Amber to Red.

Created: 18 Nov 2019, 4:33 p.m. | Last Modified: 18 Nov 2019, 4:33 p.m.

Panel Version: 0.35

Red List (low evidence)

ClinGen knowledge base: definitive association with Birt-Hogg-Dube syndrome. Not clear association with aortopathy apart from spontaneous pneumothorax overlapping with Marfan syndrome. Gene is not currently tested on Manchester TAAD panel.

Created: 25 Sep 2019, 9:34 a.m. | Last Modified: 25 Sep 2019, 9:34 a.m.

Panel Version: 0.30

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Birt-Hogg-Dube syndrome 135150; Pneumothorax, primary spontaneous 173600

Publications

• 20618353

Red List (low evidence)

135150 Birt-Hogg-Dube syndrome; 173600 primary spontaneous pneumothorax - neither of these have mention of cardiac phenotype but do mention pneumothorax being typical of Marfan syndrome

Created: 25 Mar 2019, 4:30 p.m.

Liu et al 2017 Orphanet J Rare dis 12:104 PMID:28558743 characterise several FLCN variants in a chinese Birt-Hogg-Dube cohort and comment on comparision with mutations found in Western cohorts, but do not mention any cardiac involvement

Created: 25 Mar 2019, 4:27 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

I don't know

76 year female developed type A aortic dissection. Post op investigation revealed BHD syndrome. Could the TAAD be incidental (and related to age) rather than association with FLCN?
Where is the evidence for FLCN association with TAAD? Why is it in the green list?

Created: 7 Mar 2019, 1:21 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Publications

• PMID: 24917291

I don't know

This gene was part of an initial gene list collated by Matthew Edwards Royal Brompton Hospital sent 16th Jan 2019 on behalf of the London South GLH for review by the GMS Cardiology Specialist Group. Only gene symbol from the Royal Brompton gene panel was provided - suggested initial gene rating and evidence for inclusion not provided with the list.

Created: 20 Feb 2019, 2:17 p.m.

I don't know

Comment on publications: added publications to support evidence that variants of FLCN causes primary spontaneous pneumothorax and Birt-Hogg-Dube Syndrome

Created: 11 May 2017, 2:34 p.m.

Comment on mode of inheritance: Confirmed on G2P and OMIM.

Created: 11 May 2017, 2:28 p.m.

clinical team R.Scott and A. Tucci advised this gene was taken off the Ehlers-Danlos syndrome panel, and noted FLCN should be on the Familial Thoracic Aortic Aneurysm Disease panel, which would mean it would be on our wider connective tissue panel if we decide to merge EDS and this panel plus others later on

Created: 11 May 2017, 2:27 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Pneumothorax, primary spontaneous, 173600