What are the genetic changes related to Hennekam syndrome ?
Mutations in the CCBE1 or FAT4 gene can cause Hennekam syndrome.  The CCBE1 gene provides instructions for making a protein that is found in the lattice of proteins and other molecules outside the cell (extracellular matrix). The CCBE1 protein is involved in the maturation (differentiation) and movement (migration) of immature cells called lymphangioblasts that will eventually form the lining (epithelium) of lymphatic vessels.  The function of the protein produced from the FAT4 gene is largely unknown. Research shows that the FAT4 protein may be involved in determining the position of various components within cells (cell polarity).  CCBE1 gene mutations that cause Hennekam syndrome change the three-dimensional shape of the protein and severely decrease its function. The abnormal protein cannot play its role in the formation of the lymphatic vessel epithelium. The resulting malformation of lymphatic vessels leads to lymphangiectasia, lymphedema, and other features of Hennekam syndrome. Since the lymphatic system extends throughout the body, a disruption to the vessels can affect almost any organ. Altered lymphatic development before birth may change the balance of fluids and impair normal development, contributing to many of the other signs of Hennekam syndrome such as unusual facial features.  FAT4 gene mutations that cause Hennekam syndrome result in a FAT4 protein with decreased function. Reduced FAT4 protein activity seems to impair normal development of the lymphatic system, but the mechanism is unknown.  Together, mutations in the CCBE1 and FAT4 genes are responsible for approximately half of all Hennekam syndrome cases. The cause of the remaining cases is unknown.