Capillary Malformation-Arteriovenous Malformation Syndrome

Excerpt

Clinical characteristics: Capillary malformation-arteriovenous malformation (CM-AVM) syndrome is characterized by the presence of multiple small (1-2 cm in diameter) capillary malformations mostly localized on the face and limbs. Some affected individuals also have associated arteriovenous malformations (AVMs) and/or arteriovenous fistulas (AFVs), fast-flow vascular anomalies that typically arise in the skin, muscle, bone, spine, and brain; life-threatening complications of these lesions can include bleeding, congestive heart failure, and/or neurologic consequences. Symptoms from intracranial AVMs/AVFs appear to occur early in life. Several individuals have Parkes Weber syndrome (multiple micro-AVFs associated with a cutaneous capillary stain and excessive soft-tissue and skeletal growth of an affected limb).

Diagnosis/testing: The diagnosis of CM-AVM syndrome is established in a proband with suggestive clinical findings and a heterozygous pathogenic variant in EPHB4 or RASA1 identified by molecular genetic testing.

Management: Treatment of manifestations: For capillary malformations and telangiectases that are of cosmetic concern, referral to a dermatologist. For AVMs and AVFs, the risks and benefits of intervention (embolization vs surgery) must be considered, usually with input from a multidisciplinary team (e.g., specialists in interventional radiology, neurosurgery, surgery, cardiology, and dermatology). For cardiac overload, referral to a cardiologist. For hemihyperplasia and/or leg-length discrepancy, referral to an orthopedist. Lymphangiography to evaluate for lymphatic malformations may be considered; compression stockings for those with evidence of lymphedema; epistaxis treatment includes humidification, nasal lubricants, referral to otolaryngologist, and complete blood count for evaluation of anemia.

Surveillance: Repeat imaging studies if clinical signs/symptoms of AVMs/AVFs become evident.

Evaluation of relatives at risk: Clarification of the genetic status of at-risk relatives is appropriate in order to allow early diagnosis and treatment of AVMs/AVFs to reduce/avoid secondary adverse outcomes.

Genetic counseling: CM-AVM syndrome is inherited in an autosomal dominant manner. For RASA1-CM-AVM syndrome, about 70% of affected individuals have an affected parent; about 30% have a de novo pathogenic variant. For EPHB4-CM-AVM syndrome, about 80% of affected individuals have an affected parent; about 20% have a de novo pathogenic variant. Each child of an individual with CM-AVM syndrome has a 50% chance of inheriting the pathogenic variant. Prenatal and preimplantation genetic testing are possible if the pathogenic variant has been identified in an affected family member.