Hennekam syndrome, also known as intestinal lymphagiectasia–lymphedema–mental retardation syndrome,[1] is an autosomal recessive disorder consisting of intestinal lymphangiectasia, facial anomalies, peripheral lymphedema, and mild to moderate levels of growth and intellectual disability.

[1][2] It is also known as "lymphedema-lymphangiectasia-mental retardation syndrome".

[3] Hennekam syndrome is subdivided according to the causative genetic lesion, most (or all) of which are affecting the VEGF-C/VEGFR-3 signaling pathway: The first recognition of a genetic association was with CCBE1, published by its namesake, Raoul Hennekam.

[7] The molecular mechanism of the lymphedema phenotype in CCBE1-associated cases was identified as a diminished ability of the mutated CCBE1 to accelerate and focus the activation of the primary lymphangiogenic growth factor VEGF-C.[8] Mutations in the FAT4 gene had previously been only associated with van Maldergem syndrome, but the pathogenetic molecular mechanism and the function of FAT4 within lymphangiogenesis are still unknown.