Somatic Genetic Testing Provides Diagnosis of Verrucous Venous Malformation in an Individual with Discrepant...

Verrucous venous malformation (VVM) is frequently misdiagnosed. This individual demonstrates the value of genetic testing to inform correct diagnosis. Consent was provided for retrospective chart review and publication. At birth, the affected individual had a red flat patch with overgrowth of his right hand, arm, and shoulder. The overgrowth and red color persisted and began to cause pain, which prompted his initial evaluation at age 10 years, leading to a diagnosis of a capillary vascular malformation and overgrowth. Routine magnetic resonance imaging of the right arm showed no definitive vascular anomaly. At 12 years old, hyperkeratosis prompted a biopsy for diagnosis. Pathology from 2 skin biopsies was most consistent with a capillary malformation and showed mildly acanthotic epidermis with hyperkeratosis overlying dilated, thin-walled vascular channels. We performed a 34-gene somatic genetic testing panel on the biopsy tissue. Results showed a likely pathogenic variant in the MAP3K3 gene c.674C>T, p.Ser225Phe at variant allele fraction of 4.2%-4.6% from sample 1 and 7.3%-8.0% from sample 2, confirming the diagnosis of VVM. Somatic genetic testing provided this affected individual with the diagnosis of VVM when radiology, pathology, and clinical findings were discrepant. This new genetic diagnosis influences treatment and prognosis.