pyrimidinones and Arteriovenous-Malformations

Capillary malformation-arteriovenous malformation (CM-AVM) syndrome is an autosomal dominant condition characterized by multifocal, noncontiguous pink patches on the skin that often have a surrounding pale halo. In some cases, an association with a fast flow, arteriovenous malformation (AVM) can be identified. Here, we describe a case report of a 16-year-old woman with CM-AVM syndrome and significant cardiac compromise successfully treated with trametinib, a mitogen-activated protein kinase (MEK) inhibitor.

Topics: Adolescent; Arteriovenous Malformations; Capillaries; Female; Humans; p120 GTPase Activating Protein; Port-Wine Stain; Pyridones; Pyrimidinones

Arteriovenous malformations (AVMs) have recently been reported to have a high incidence of somatic KRAS mutations suggesting potential for treatment with mitogen-activated protein kinase inhibitors. In this case report, we describe genotype-targeted treatment of a KRAS mutant metameric AVM in a patient with Cobb syndrome using the mitogen-activated protein kinase inhibitor trametinib. Therapeutic response was monitored with phase-contrast magnetic resonance angiography to quantify AVM arterial inflow as an imaging biomarker. Treatment with trametinib resulted in a substantial decrease in blood flow to the AVM, with a >75% reduction in arterial inflow after 6 months of trametinib therapy.

Topics: Adolescent; Amino Acid Sequence; Arteriovenous Malformations; Drug Delivery Systems; Genotype; Humans; Male; Protein Kinase Inhibitors; Proto-Oncogene Proteins p21(ras); Pyridones; Pyrimidinones; Spinal Cord Diseases; Syndrome; Treatment Outcome

Topics: Arteriovenous Malformations; Child; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Genotype; Humans; Microtubule-Associated Proteins; Molecular Targeted Therapy; Pyridones; Pyrimidinones; Severity of Illness Index; Thoracic Wall; Treatment Outcome