Thoracic aortic aneurysm or dissection

Gene: FBN2

Green List (high evidence)

Present on Wessex aortopathy panel.
Associated with congenital contractural arachnodactyly, which has significant phenotypic overlap with Marfan syndrome.

Created: 8 May 2019, 1:38 p.m.

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

Green List (high evidence)

121050 Contractural arachnodactyly - CTD including aortic root dilatation, patent ductus arteriosus, BAV, VSD, ASD, mitral valve prolapse and mitral regurgitation

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

Wooderchak-Donahue et al 2015 Am J Med Genet A 167A:1747 PMID:25944730 5 missense variants identified in Marfan/Marfan-like cohort: 3302A>G Asn1101Ser, 3793G>A Glu1265Lys, 4454A>G Asp1485Gly, 4657C>T Arg1553Cys, 5627G>C Cys1876Ser - all reported as VUS. Callewaert et al 2009 Hum Mutat 30:334 PMID:19006240 review FBN2 variants in contractural arachnodactyly and comment on involvement of aortopathy in phenotype of more recently described cases.

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

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

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

Green List (high evidence)

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, 10:49 a.m.

I don't know

Strong association with contractural arachnodactyly. However, in the context of familial thoracic aortic aneurysm, evidence is much weaker with only a single case report complicated with Aortic Dilatation and Dissection (see PMID above) and other weak association with progressive aortic dilatation (ref within above case report).

Created: 9 Feb 2016, 3:38 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
#121050 - Contractural arachnodactyly, congenital; #616118- Macular degeneration, early-onset

Publications

• PMID: 25975422

I don't know

Reported dilatations are infrequent and relatively mild. No reported dissections associated with FBN2 mutations to date. Although strong evidence for causation of CCA and associated defects, evidence for involvement in FTAAD is less clear.

Created: 13 Nov 2015, 4:31 p.m.