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capillary malformation-arteriovenous malformation 2 - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

capillary malformation-arteriovenous malformation 2

MONDO:0020785

Also known as:CMAVM2

Overview

GeneticsAutosomal dominant · EPHB4 (chr 7)

Clinical Presentation

Built from Human Phenotype Ontology (HPO) phenotype annotations and GeneReviews clinical descriptions. Features represent findings documented across known cases — not an exhaustive list of possible symptoms.

Features include always present findings: Capillary malformation; and rarely findings: Vein of Galen aneurysmal malformation. 3 total HPO annotations.

Organ System	Phenotype Count	Example Features
Skin	1	Telangiectasia

Genetic Landscape

Assembled from HGNC gene records, ClinGen gene-disease validity evidence, and ClinVar pathogenic variant data. Validity classifications reflect the strength of published evidence linking each gene to this disease.

EPHB4 encodes EPH receptor B4 (987 aa). Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. Highest expression in Uterus (133.8 TPM) and Cervix Endocervix (110.2 TPM).

Capillary malformation-arteriovenous malformation 2 is associated with mutations in the EPHB4 gene on chromosome 7.

EPHB4 is classified as a druggable target (Clinically Actionable, Druggable Genome, Enzyme, Kinase, and Tyrosine Kinase categories) with score 5.4.

GeneReviews

Diagnosis

Drawn from GeneReviews diagnostic guidelines, newborn screening panel status (RUSP), and ClinGen gene-disease validity classifications. Reflects current clinical evidence and consensus where available.

GeneReviews

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"

Treatment

Compiled from FDA-approved drug records, orphan drug designations, and FDA Adverse Event Reporting System (FAERS) safety data. GeneReviews management guidance is included where available.

No approved treatments are currently available for capillary malformation-arteriovenous malformation 2. The disease remains an area of unmet medical need.

GeneReviews

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

Prognosis

Based on GeneReviews surveillance recommendations, HPO phenotype frequency and severity annotations, and published prevalence estimates from Orphanet and OMIM.

GeneReviews

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"

Phenotype severity distribution: 1 always present feature.

Research Landscape

Sourced from ClinicalTrials.gov and PubMed. Publication types are classified using NLM-curated article metadata; research type breakdowns reflect the nature of published work for this disease.

No clinical trials have been registered for capillary malformation-arteriovenous malformation 2.

13 publications have been identified in PubMed for capillary malformation-arteriovenous malformation 2. Research spans Case Report / Case Series (77%), Review / Meta-Analysis (8%), and Clinical Trial Publication (8%).

Research Type	Count	% of Total
Patient case studies	10	77%

Data assembled from 6 of 12 sources · Last updated Sep 19, 2026, 8:01 AM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

External Resources

OMIM

Online Mendelian Inheritance in Man

OMIM:618196

GARD

Genetic and Rare Diseases Info Center

GARD:16307

Questions for Your Care Team

→Should I pursue genetic testing for EPHB4, and what would the results mean for my family?
→Are there specialists or centers of excellence for this condition in my area?
→Is there a patient registry I should consider joining?

← Back to All Diseases

Differential Diagnosis

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

Gene(s)	Differential Disorder	MOI	Clinical Features of Differential Disorder
Hereditary hemorrhagic telangiectasia	AD	Multiple AVMs that lack intervening capillaries result in direct connections between arteries veins	Spontaneous recurrent nosebleeds (epistaxis) are more common.; Telangiectases generally only on lips, nose, hands; ~25% may have GI bleeding later in life.; Large capillary malformations are not typical.
GNAQ	Sturge-Weber syndrome (SWS) (OMIM 185300)	Seefootnote 2.	Intracranial vascular anomaly3
PIK3CA	Klippel-Trenaunay-Weber syndrome5	Seefootnote 6.	CMs hypertrophy of the related bones soft tissues
PTEN	PTEN hamartoma tumor syndromes8	AD	Overgrowth fast-flow lesions
Multiple cutaneous and mucosal venous malformations	AD	Cutaneous VMs can be mistaken for CMs.	Small, multifocal bluish cutaneous /or mucosal VMs, usually present at birth. New lesions appear w/time.; Small lesions are usually asymptomatic; larger lesions can invade subcutaneous muscle cause pain.
GLMN	Hereditary glomuvenous malformations (GVMs) (OMIM 138000)	AD	Cutaneous VMs can be mistaken for CMs.

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

Manifestation/Concern	Treatment	Considerations/Other
CMs telangiectases	Referral to dermatologist	To evaluate CMs of cosmetic concern discuss risks benefits of intervention
AVMs/AVFs	Multidisciplinary team incl specialists in interventional radiology, neurosurgery, surgery, cardiology, dermatology depending on location symptoms	To determine treatment (e.g., embolization vs surgery); Risks benefits of intervention for AVMs AVFs must be considered.
Cardiac overload	Referral to cardiologist	—
Hemihyperplasia /or leg length discrepancy	Referral to orthopedist	Consider:; Lymphangiography to evaluate for lymphatic malformations;; Compression stockings for those w/evidence of lymphedema.
Epistaxis (nosebleeds)	Humidification nasal lubricants; referral to otolaryngologist	If epistaxis, perform complete blood count for eval of anemia. The clinician should have a low threshold to repeat imaging studies if clinical signs/symptoms of AVMs/AVFs become evident over time.

Kisho

capillary malformation-arteriovenous malformation 2

Overview

Clinical Presentation

Genetic Landscape

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Prognosis

Surveillance Guidelines

Research Landscape

Medical References

External Resources

OMIM

GARD

Questions for Your Care Team

Questions for Your Care Team

Clinical Guidance

Capillary malformations

Explore clinical features

Penetrance

Differential Diagnosis

Clinical Trials

Recent Publications

capillary malformation-arteriovenous malformation 2

Overview

Clinical Presentation

Genetic Landscape

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Prognosis

Surveillance Guidelines

Research Landscape

Medical References

External Resources

OMIM

GARD

Related Diseases

Questions for Your Care Team

Questions for Your Care Team

Clinical Guidance

Capillary malformations

Explore clinical features

Penetrance

Differential Diagnosis

Clinical Trials

Recent Publications