Multifocal Sporadic Venous Malformations in a Child Caused by a Novel Somatic Double Mutation of the TEK Gene: A Case Report and Literature Review.

backgroundMultifocal sporadic venous malformations (MSVM) are a rare and severe subtype of venous malformations (VMs). Although somatic mutations in the TEK gene are frequently implicated in VMs, the clinical and molecular significance of harboring two distinct somatic mutations within a single lesion remains poorly understood.

methodsDNA was extracted from both the lesion and peripheral blood, followed by whole-exome sequencing (WES) and structural modeling of the TIE2 protein.

resultsThe proband, a 6-year-old Chinese boy, presented at birth with soft-tissue swelling of the hands and occipital region, which progressively involved the tongue, neck, trunk, extremities, and external genitalia. Imaging demonstrated extensive venous ectasia infiltrating subcutaneous and muscular layers. Despite 20 sessions of sclerotherapy, the lesions continued to progress and showed a strong tendency for recurrence. WES of the lesion revealed two pathogenic somatic mutations in the TEK gene: c.2740C>T (p.L914F) and c.2545C>T (p.R849W), which weren't detected in peripheral blood. Structural modeling suggested no major global conformational changes but showed possible local structural differences within the kinase domain. The double-mutant variant exhibited predicted enhanced hydrogen bonding at the mutation sites, potentially contributing to local structural rearrangements and altered conformational stability.

conclusionThis report describes a previously unreported case of dual somatic TEK mutations in MSVM. The findings expand the mutational spectrum of TEK-related VMs and underscore the importance of lesion-based genetic testing in complex cases.