Hereditary haemorrhagic telangiectasia

Gene: EPHB4

Green List (high evidence)

On CGGL Royal Brompton HHT diagnostic panel. Pathogenic variants are a cause of Capillary malformation-arteriovenous malformation 2, a differential diagnosis of HHT

Created: 22 Sep 2019, 8:03 p.m. | Last Modified: 22 Sep 2019, 8:03 p.m.

Panel Version: 1.51

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

Phenotypes
OMIM: 618196 Capillary malformation-arteriovenous malformation 2; 617300 Lymphatic malformation 7

Publications

• 28687708
• 29444212
• 30760892

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

Comment on list classification: Changed from Amber to Green. Appropriate phenotype, sufficient cases and external expert review all support gene-disease association and relevance to this panel to rate gene as Green.

Created: 27 Jun 2019, 10:53 a.m. | Last Modified: 27 Jun 2019, 10:53 a.m.

Panel Version: 1.49

Comment on phenotypes: Added phenotypes suggested from expert review that indicate relevance to inclusion on the Hereditary haemorrhagic telangiectasia panel

Created: 27 Jun 2019, 10:48 a.m. | Last Modified: 27 Jun 2019, 10:48 a.m.

Panel Version: 1.47

Comment on publications: Added PMID: 30760892 from external reviewer to support upgrading of gene to Green

Created: 27 Jun 2019, 10:46 a.m. | Last Modified: 27 Jun 2019, 10:46 a.m.

Panel Version: 1.46

Green List (high evidence)

Emerging as an HHT diagnostic mimic in patients sequenced through 100K with "HHT-like" telangiectasia. Note the syndrome is termed Capillary Malformation-Arteriovenous Malformation (CM-AVM2, PMID: 30760892) but a pathogenic EPHB4 variant was also identified in seven unrelated ENG/ACVRL1/SMAD4 negative cases presenting with features that might be considered suspicious of HHT (epistaxis, telangiectasia, [with significant differences in cutaneous presentation to HHT] and occasional cerebral malformations, PMID: 28687708).

Created: 24 Jun 2019, 12:35 a.m. | Last Modified: 24 Jun 2019, 12:35 a.m.

Panel Version: 1.44

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

Phenotypes
capillary malformation, epistaxis, telangiectasia, cerebral AVM

Publications

• PMID: 28687708 PMID: 30760892

I don't know

At least one family in 100k recruited under HHT has a mutation in this gene as it's an overlap condition. Consider whether to include with the GLH specialist group for GMS diagnostic analysis.
Sources: Other

Created: 21 Jun 2019, 12:26 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Capillary malformation-arteriovenous malformation 2; 618196

Publications

• 28687708
• 28730721