Thoracic aortic aneurysm or dissection

Gene: FLNA

Comment on mode of inheritance: MOI was corrected.

Created: 30 Sep 2019, 10:51 a.m. | Last Modified: 30 Sep 2019, 10:51 a.m.

Panel Version: 1.97

Green List (high evidence)

314400 Cardiac valvular dysplasia, X-linked; 300048 Congenital short bowel syndrome; 309350 Melnick-Needles syndrome all have aortic involvement

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

Chen et al 2018 Am J Med Genet A 176:337 PMID:29334594 examine patients with FLNA for cardiac features and found that 18% had thoracic aortic aneurysm/dilation and 57% had other cardiac abnormalites. This included two patients who died of aortic rupture at aortic diameters smaller than that reccomended for surgery in other aortopathies.

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

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

Comment on phenotypes: TAAD phenotype taken from Emory sequencing panel.

Created: 29 Jun 2017, noon

FLNA is associated with a syndromic form of TAAD, namely the periventricular nodular heterotopia type 1 (PVNH1; also known as the Ehlers-Danlos variant of PVNH, MIM:300049). FLNA is confirmed DD-G2P gene for MIM:300049, though FLNA only explains a small number of the X-linked TAAD families.

Created: 29 Jun 2017, 11:58 a.m.

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.

Not on the Inherited Cardiac Condition Genes panel for Familial aortic anuerysm reported in: Development of a Comprehensive Sequencing Assay for Inherited Cardiac Condition Genes, Pua et al, Journal of Cardiovascular Translational Research, online Feb 2016 (doi:10.​1007/​s12265-016-9673-5). The panel contains disease-causing, putatively pathogenic, research and phenocopy genes.

Created: 19 Feb 2016, 10:57 a.m.

Green List (high evidence)

FLNA mutations initially associated with periventricular nodular heterotopias (OMIM 300049). More recently, patients with mitral valve disease, aortic root dilatation, and joint hypermobility without periventricular nodular heterotopias have been associated with FLNA mutations (see ref above, also: http://www.ashg.org/2013meeting/abstracts/fulltext/f130120800.htm)

Mode of inheritance: FLNA heterozygous female mice had variable clinical features of less severity compared to FLNA-Null mice with features suggesting vascular remodelling failure (coarse and dilated vasculature, haemorrhage and oedema)- PMID: 17172441

Created: 14 Feb 2016, 11:56 a.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
300537- Heterotopia, periventricular, ED variant; 300049- Heterotopia, periventricular; 314400- Cardiac valvular dysplasia, X-linked

Publications

• PMID: 9883725
• 26188975
• 17172441