Penetrance

EPHB4. Penetrance of EPHB4-CM-AVM syndrome was reported to be 93% (102 of 110 individuals) in one study by . RASA1. Penetrance is 90%-99% for RASA1-CM-AVM syndrome. determined that 55 of 57 individuals heterozygous for a germline RASA1 pathogenic variant were affected. determined that 136 of 138 individuals heterozygous for a germline RASA1 pathogenic variant had multiple CMs.

Source: GeneReviews — "Capillary Malformation-Arteriovenous Malformation Syndrome"

Diagnostic Criteria

Diagnostic criteria for capillary malformation-arteriovenous malformation (CM-AVM) syndrome have been proposed but not systematically evaluated .

Suggestive Findings

CM-AVM syndrome should be suspected in probands who have any of the following:

Source: GeneReviews — "Capillary Malformation-Arteriovenous Malformation Syndrome"

Differential Diagnosis

Table 3. Other Genes of Interest in the Differential Diagnosis of Capillary Malformation-Arteriovenous Malformation (CV-AVM) Syndrome

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease and needs of an individual diagnosed with capillary malformation-arteriovenous malformation (CM-AVM) syndrome, the following evaluations (if not performed as part of the evaluation that led to the diagnosis) are recommended: • Medical history and physical examination with a focus on symptoms and findings secondary to arteriovenous malformations/arteriovenous fistulas (AVMs/AVFs) • Brain imaging – if not already performed – to identify AVMs/AVFs (e.g., vein of Galen aneurysms and other intracranial AVMs) to allow early identification of macrofistulas that can be treated prior to the development of symptoms • Consideration of spine imaging to identify and characterize AVMs/AVFs. Currently no consensus protocols for radiographic evaluation of individuals with CM-AVM syndrome have been developed; therefore, discussion with a radiologist is recommended in order to develop an appropriate plan for imaging based on the patient's age and the capabilities and experience of the imaging facility. • Consideration of further imaging in individuals with evidence of cardiac overload, to look for causative AVMs/AVFs • Evaluation for evidence of epistaxis (nosebleeds), and if present, referral to otolaryngologist as appropriate. If epistaxis is present, consider complete blood count for evaluation of anemia. • Consultation with a clinical geneticist and/or genetic counselor Treatment of Manifestations Table 4. Treatment of Manifestations in Individuals with CM-AVM Syndrome

Source: GeneReviews — "Capillary Malformation-Arteriovenous Malformation Syndrome"

Surveillance Guidelines

The clinician should have a low threshold to repeat imaging studies if clinical signs/symptoms of AVMs/AVFs become evident over time.

Source: GeneReviews — "Capillary Malformation-Arteriovenous Malformation Syndrome"