Search for RASA1 Variants in Capillary Malformations of the Legs in 113 Children: Results from the French National Paediatric Cohort CONAPE

Abstract

Patients with an inherited autosomal-dominant disorder, capillary malformation-arteriovenous malformation (CM-AVM), frequently have mutations in Ras P21 protein activator 1 (RASA1). The aims of this study were to determine the prevalence of germline RASA1 variants in a French multicentre national cohort of children, age range 2-12 years, with sporadic occurrence of capillary malformation (CM) of the legs, whatever the associated abnormalities, and to identify genotype-phenotype correlates. DNA was extracted from leukocytes in blood samples, purified and amplified, and all exons of the RASA1 gene were analysed. Among 113 children analysed, 7 had heterozygous variants (6.1%). Four different variants were identified; 2 were new. In children with RASA1 variants, CMs were more frequently bilateral and multifocal. In conclusion, RASA1 variants are rarely found in children with sporadic CM of lower limbs without CM-AVM syndrome. CMs in this study were heterogeneous, and no disease-causing relationship could be proven.

An asymptomatic stain on the forehead

“…Capillary malformation-arteriovenous malformation (CM-AVM) syndrome [1] (OMIM 608354) is an autosomal dominant disorder described by Eerola et al [2], characterized by the presence of multiple, small (1-2 cm in diameter), roundto-oval capillary malformations with a reddish to pink color (often with a white surrounding halo) which are mostly located on the face and limbs [3]. One-third of the patients also have fast-flow arteriovenous malformations (AVMs) or arteriovenous fistulas (AVFs) which may be located in soft tissue, bone, muscle, brain or spine, and can cause life-threatening complications such as bleeding, neurologic impairment and congestive heart failure.…”

RASA1 Variants in Capillary Malformations of Children: A Comment to Maruani A et al.

“…In conclusion, the large-scale molecular study of CMs presented by Maruani et al (1) shows that focusing on a single gene, such as RASA1, will yield less specific results. As an initial step, it may be preferable to categorize CMs according to their dermatological criteria, which would simplify the search for the molecular basis of a given disorder.…”

“…In 7 children they found heterozygosity for a RASA1 variant. Maruani et al (1) use the presently prevailing classification of the International Society for the Study of Vascular Anomalies (ISSVA) (2,3). However, this nomenclature does not discriminate between CMs that have specifically different dermatological criteria (4).…”

Capillary Malformation-arteriovenous Malformation Type 2: A Case Report and Review

“…Both conditions present with cutaneous CMs that can be associated with the presence of 1 or more AVMs/AVFs. The CMs are described as macular, possible multifocal, light red, red or violet lesions varying in size typically from 1 to 3 cm in diameter (1)(2)(3)(8)(9)(10)(11). Larger lesions can occur, and CMs up to 15 cm in diameter have been described (8).…”