Clinical Spectrum of Capillary Malformation–Arteriovenous Malformation Syndrome Presenting to a Pediatric Dermatology Practice: A Retrospective Study

Abstract

Capillary malformation-arteriovenous malformation syndrome (CM-AVM) is an autosomal dominant disorder caused by RASA1 mutations. The prevalence and phenotypic spectrum are unknown. Evaluation of patients with multiple CMs is challenging because associated AVMs can be life threatening. The objective of this study was to describe the clinical characteristics of children presenting with features of CM-AVM to an academic pediatric dermatology practice. After institutional review board approval was received, a retrospective chart review was performed of patients presenting between 2009 and 2012 with features of CM-AVM. We report nine cases. Presenting symptoms ranged from extensive vascular stains and cardiac failure to CMs noted incidentally during routine skin examination. All demonstrated multiple CMs, two had Parkes Weber syndrome, and two had multiple infantile hemangiomas. Seven patients had family histories of multiple CMs; three had family histories of large, atypical CMs. Six had personal or family histories of AVMs. Genetic evaluation was recommended for all and was pursued by six families; four RASA1 mutations were identified, including one de novo. Consultations with neurology, cardiology, and orthopedics were recommended. Most patients (89%) have not required treatment to date. CM-AVM is an underrecognized condition with a wide clinical spectrum that often presents in childhood. Further evaluation may be indicated in patients with multiple CMs. This study is limited by its small and retrospective nature.

Multifocal capillary malformations in an older, asymptomatic child with a novel RASA 1 mutation

“…Familial occurrence of multiple CMs was first described in 1949; however, it was only in 2002 that molecular characterization of a subset of these patients led to the identification of heterozygous mutations in RASA1 . To date, > 100 mutations in this gene have been reported, and no genotype–phenotype correlation is seen . Approximately 30% of RASA1 mutation carriers have a de novo mutation, and the penetrance is high (96.5%) …”

“…2 To date, > 100 mutations in this gene have been reported, and no genotype-phenotype correlation is seen. 1,3 Approximately 30% of RASA1 mutation carriers have a de novo mutation, and the penetrance is high (96.5%). 4 RASA1 (ras p21 protein activator 1) encodes the protein p120 RasGAP, an important regulator of vascular cellular differentiation and proliferation.…”

Strategies in Interventional Radiology: Formation of an Interdisciplinary Center of Vascular Anomalies – Chances and Challenges for Effective and Efficient Patient Management

“…However, there is no generally accepted definition for the differentiation between slow-flow and fast-flow malformations. The lack of flow voids on the T2 image in MRI is considered to be a "slow-flow" lesion by some specialists [18,19]. The percentage of infants and young adults up to 18 years of age at the interdisciplinary center for vascular anomalies at the University Medical Center Mannheim is 55 % while the percentage of adults between 20 to 70 years of age is 45 %.…”

Good response to pulsed dye laser in patients with capillary malformation‐arteriovenous malformation syndrome (CM‐AVM)

“…Capillary malformation‐arteriovenous malformation syndrome (CM‐AVM) is an autosomal dominant disorder caused by heterozygous mutations in RASA1 and EPHB4 . The estimated incidence is about 1/10.000 in northern Europeans, although its true prevalence remains unknown, and it is probably underdiagnosed . Up to a third of patients have associated fast‐flow lesions such as arteriovenous malformations (AVM) and arteriovenous fistulae (AVF) that can be cutaneous, subcutaneous, intramuscular, intraosseus, intracerebral, or intraspinal.…”

“…4 The estimated incidence is about 1/10.000 in northern Europeans, although its true prevalence remains unknown, and it is probably underdiagnosed. 5 Up to a third of patients have associated fast-flow lesions such as arteriovenous malformations (AVM) and arteriovenous fistulae (AVF) that can be cutaneous, subcutaneous, intramuscular, intraosseus, intracerebral, or intraspinal. Visceral AVMs can be life-threatening, emphasizing the need for early diagnosis.…”