Genotype-Guided Medical Treatment of an Arteriovenous Malformation in a Child

Abstract

Importance:: Genetic testing results can provide guidance in developing personalized treatment plans for patients with vascular anomalies.

Objective:: To explore the efficacy of tramitinib in the treatment of an extracranial arteriovenous malformation with a somatic MAP2K1 mutation.

Design:: Case report of a child with an arteriovenousu malformation that was successfully treated with trametinib after identification of a specific somatic mutation within the malformation.

Setting:: Outpatient Vascular Anomalies Clinic, Stanford University, Stanford, CA.

Participant:: An 11-year-old girl with an arteriovenous malformation on the back who had failed treatment with systemic sirolimus.

Intervention:: Paired exome sequencing using tumor and saliva DNA was performed and identified a somatic mutation within the MAP2K1 gene. The patient was then transitioned to trametinib at a starting dose of 0.5 mg once daily then increased to 0.5 mg twice daily after one month.

Main Outcome:: Tramitinib was effective in reducing the size of and blood flow to the arteriovenous malformation.

Results:: After one month on tramitinib, the patient and parents noticed the malformation reduced in size and became lighter in color. After six months of treatment, quantitative analyses were performed using magnetic resonance imaging and showed significant interval decrease in the volume of the malformation and the caliber of the vasculature compared to prior examinations. To date, she has tolerated the treatment well with development of a mild acneiform eruption responding well to over the counter adapalene and benzoyl peroxide.

Conclusion and Relevance:: Management of arteriovenous malformations is very challenging due to almost inevitable disease progression and high recurrence rates after surgical resection. The discovery of a somatic mutation associated with this arteriovenous malformation provided guidance for targeted therapy. Trametinib may be a promising targeted therapeutic option for sporadic extracranial arteriovenous malformations harboring MAP2K1 mutations.

Figures

Figure 1:

Clinical presentation and imaging studies of an arteriovenous malformation on the left scapular region of an 11 year-old girl. Clinical photos at (A) baseline; (B) after 8 months of sirolimus treatment; and (C) after 6 months trametinib treatment are shown. In addition, corelating magnetic resonance imaging (D-F).

Figure 2:

Volumetric analysis of arteriovenous malformation response to sirolimus and trametinib treatment.