Mutations in gene RASA1 have been historically associated with capillary malformation-arteriovenous malformation, but sporadic reports of lymphatic involvement have yet to be investigated in detail.
Maternal and fetal capillary malformation-arteriovenous malformation (CM-AVM) due to a novel RASA1 mutation presenting with prenatal non-immune hydrops fetalis.
A germline mutation was identified in 23 probands (53.5 ± 14.9%): 8 in ENG (34.8 ± 14.2%), 1 in ACVRL1 (4.3 ± 6%) leading to a diagnosis of HHT, and 14 in RASA1 (60.9 ± 14.4%) leading to a diagnosis of capillary malformation/arteriovenous malformation type 1.No EphB4 gene mutation was identified.
In humans, RASA1 mutations cause capillary malformation-arteriovenous malformation (CM-AVM); whether it also functions as a regulator of the lymphatic vasculature is unknown.
Recently a rare form of hereditary vascular malformation termed capillary malformation-arteriovenous malformation (CM-AVM) was shown to be caused by heterozygous mutations in RASA1, encoding RAS p21 protein activator 1.
RASA1, a regulator of cardiovascular development, is involved in this pathway and its haploinsufficiency (due to heterozygous mutations) has been identified as the underlying etiology of the autosomal dominant capillary malformation/arteriovenous malformation (CM/AVM).
We report the follow-up of these three cases with RASA1 gene mutation and comment on the possible role of evaluation for vascular lesions and capillary malformation-arteriovenous malformation syndrome in patients and their families, with intracranial fast-flow shunts.
The heredity of PWS was 27% (65/240).Twenty-one patients with a positive family history and relatives had no CM-AVM phenotype for mutations in the RASA1 gene.
Mutations in the RASA1 gene have been shown to underlie the capillary malformation-arterio-venous malformation (CM-AVM) syndrome, sometimes presenting with PWS.
We present the case of a child with RASA1-negative CM-AVM syndrome with a de novo missense mutation in EPHB4, a transmembrane tyrosine kinase receptor essential for vasculogenesis.