Hennekam syndrome

Hennekam syndrome is an autosomal recessive disorder combining intestinal lymphangiectasia, distinctive facial features, lymphedema of the limbs, and mild to moderate growth and intellectual disability. It results from disruption of the VEGF-C and VEGFR-3 signaling pathway that governs lymphatic vessel development, with three known genetic types: type 1 from mutations in the CCBE1 gene, type 2 from mutations in FAT4, and type 3 from mutations in ADAMTS3. In type 1, the altered CCBE1 protein has a reduced ability to activate VEGF-C, the principal growth factor for lymph vessel formation, while the molecular mechanism in the FAT4 and ADAMTS3 forms is less well understood. The syndrome is named for Raoul Hennekam, who first documented it and identified its link to CCBE1.