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.
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.
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.
Haploinsufficiency of RASA1, located on chromosome 5q14.3, has been identified as the etiology underlying the disorder capillary malformation-arteriovenous malformation (CM-AVM).
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.
The objective of the study was to identify somatic RASA1 "second hits" from vascular malformations associated with CM-AVM syndrome, and describe phenotypic variability.
These three individuals had epistaxis and dermal lesions that were described as telangiectases but whose location and appearance resembled lesions described in some individuals with RASA1-related disorders (capillary malformation-arteriovenous malformation syndrome).