Fetal hydrops

Gene: RASA1

Green List (high evidence)

Comment on list classification: There is sufficient evidence available (~25 unrelated cases) for the promotion of this gene to green rating on this panel.

Created: 10 Oct 2025, 2:13 p.m. | Last Modified: 10 Oct 2025, 2:13 p.m.

Panel Version: 1.91

Comment on phenotypes: OMIM phenotype last accessed on 10 October 2025.

Created: 10 Oct 2025, 2:13 p.m. | Last Modified: 10 Oct 2025, 2:13 p.m.

Panel Version: 1.90

PMID:36980822 (2023) reviewed 21 previously published cases with prenatal presentation of Capillary malformation-arteriovenous malformation (CM-AVM) and with pathogenic RASA1 variants. In addition, it reported four unrelated paediatric cases of molecularly confirmed CM-AVM syndrome which manifested during the prenatal period. They were all identified with monoallelic RASA1 variants.

This gene has been associated with relevant phenotype in OMIM (MIM #608354) and Gene2Phenotype (with 'limited' rating on the DD panel).

Created: 10 Oct 2025, 2:12 p.m. | Last Modified: 10 Oct 2025, 2:12 p.m.

Panel Version: 1.89

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Capillary malformation-arteriovenous malformation 1, OMIM:608354; capillary malformation-arteriovenous malformation 1, MONDO:0020783

Publications

• 36980822

Green List (high evidence)

Reported in 4 individuals in this paper with hydrops/chylothorax (PMID:36980822). Variants in this gene have been reported diagnostically in Exeter.

Created: 30 Jul 2025, 12:03 p.m. | Last Modified: 30 Jul 2025, 12:03 p.m.

Panel Version: 1.89

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
hydrops; chylothorax; Capillary malformation-arteriovenous malformation 1

Publications

• PMID:36980822

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

Green List (high evidence)

It has been clearly demonstrated that RASA1-related CM-AVM is caused by pLoF and missense variants as well as whole gene deletions and can incorporate lymphatic malformations and that these can present at the fetal stage with chylothorax, ascites, NIHF, and increased nuchal translucency.

I indicate a reduced penetrance, as the presence of this disorder can be missed entirely in affected parents due to a very variable expressivity. As such, caution is warranted when trio data is being filtered.
Sources: Literature

Created: 18 Sep 2024, 2:09 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
capillary malformation-arteriovenous malformation-1 (CMAVM1, OMIM # 608354)

Publications

• 36980822
• 33608416
• 24038909

Mode of pathogenicity
Other

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