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Images in Dermatology
April 24, 2019

Capillary Malformation–Arteriovenous Malformation Syndrome

Author Affiliations
  • 1Division of Dermatology, Department of Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, Ontario, Canada
  • 2Division of Community Pediatrics, Department of Pediatrics, Alberta Children’s Hospital, Calgary, Alberta, Canada
JAMA Dermatol. 2019;155(6):733. doi:10.1001/jamadermatol.2019.0319

A 6-year-old boy presented with multiple erythematous geographic patches (largest, 4 × 2 cm), many with a surrounding halo of pallor, on his extremities, scalp, and torso (Figure). Some lesions were present at birth, but his parents clearly described an increasing number over time. Magnetic resonance angiography examination of his brain and spinal cord, and ultrasound of the larger lesions did not reveal any associated arteriovenous malformations. Genetic testing revealed a mutation in the RASA1 gene (a negative regulator of the RAS signaling pathway), and the diagnosis of capillary malformation–arteriovenous malformation (CM-AVM) syndrome was confirmed. Neither parent carried the mutation.

Characteristic Geographic Red-Brown Patch and Macule With Halo of Blanching
Characteristic Geographic Red-Brown Patch and Macule With Halo of Blanching

Multiple erythematous geographic patches, the largest of which was 4 × 2 cm, were seen on the patient’s extremities, scalp, and torso.

This relatively newly recognized autosomal dominant disorder has a broad clinical spectrum1 and is likely underrecognized because clinicians may pay little attention to asymptomatic capillary malformations (CMs), assuming they have been present since birth. About 30% of patients have a de novo mutation,1 and it has been suggested that the observed phenotypic variability is due to a somatic second hit on a germline RASA1 mutation that may occur during fetal development.2

Importantly, in almost one-third of patients, CM-AVM syndrome can be associated with fast flow vascular anomalies (eg, arteriovenous malformations [AVMs] and arteriovenous fistulas [AVFs]) in the skin, muscle, bone, brain, and spine, which can cause life-threatening complications such as bleeding, congestive heart failure, and neurologic sequelae.3 The AVMs and AVFs can lead to overgrowth of the affected soft tissue, bone, or brain.1RASA1 germline mutations are also found in Parkes-Weber syndrome, which is characterized by cutaneous CMs associated with underlying soft tissue and bony hypertrophy owing to micro-AVFs.1 In these patients, the second somatic mutation may occur earlier in fetal development and explain its more localized distribution.

An increasing number of atypical CMs on the skin may be the only sign of CM-AVM syndrome and should alert the clinician to further investigate for the presence of AVMs or AVFs. The characteristic blanched halo suggests an associated steal phenomenon, and increased blood flow can be seen on lesional Doppler ultrasound3; however, the CMs of CM-AVM remain stable and do not progress to AVMs over time.3 Exercise caution when treating cutaneous CMs in this syndrome with pulsed dye laser because this may activate underlying arteriolovenular malformations.4 Imaging of the brain and spine is recommended at diagnosis and should be repeated if new symptoms develop (eg, severe headaches, seizures, hydrocephalus, neurologic deficits, cardiac failure).1 Consultation with radiology is recommended to define the optimal imaging protocol.1 To date, no patients with normal screening imaging results have been reported to develop fast-flow malformations over time.1

The present case is a classic presentation of CM-AVM syndrome without associated extracutaneous fast-flow malformations. The patient has regular dermatology follow-up, and no treatment is planned for his cutaneous CMs at this time.

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Article Information

Corresponding Author: Michele L. Ramien, MDCM, Division of Community Pediatrics, Department of Pediatrics, Alberta Children’s Hospital, 28 Oki Dr NW, Calgary, Alberta T2N 1Z2, Canada (michele.ramien@albertahealthservices.ca).

Published Online: April 24, 2019. doi:10.1001/jamadermatol.2019.0319

Conflict of Interest Disclosures: None reported.

Additional Contributions: We thank the patient’s family for granting permission to publish this information.

Bayrak-Toydemir  P, Stevenson  D. RASA1-Related Disorders. In: Adam  MP, Ardinger  HH, Pagon  RA,  et al, eds.  GeneReviews®. Seattle, WA: University of Washington; 2011. https://www.ncbi.nlm.nih.gov/books/NBK52764/. Accessed March 15, 2019.
Macmurdo  CF, Wooderchak-Donahue  W, Bayrak-Toydemir  P,  et al.  RASA1 somatic mutation and variable expressivity in capillary malformation/arteriovenous malformation (CM/AVM) syndrome.  Am J Med Genet A. 2016;170(6):1450-1454. PubMedGoogle ScholarCrossref
Revencu  N, Boon  LM, Mendola  A,  et al.  RASA1 mutations and associated phenotypes in 68 families with capillary malformation–arteriovenous malformation.  Hum Mutat. 2013;34(12):1632-1641. PubMedGoogle ScholarCrossref
Weitz  NA, Lauren  CT, Behr  GG,  et al.  Clinical spectrum of capillary malformation–arteriovenous malformation syndrome presenting to a pediatric dermatology practice.  Pediatr Dermatol. 2015;32(1):76-84. PubMedGoogle ScholarCrossref