Hennekam syndrome ... (Hennekam syndrome) - Genes CCBE1 or FAT4.
Hennekam syndrome is a hereditary disorder due to malformation of the lymphatic system. Signs and symptoms of the syndrome include linfangiectasia Hennekam, lymphedema and unusual facial features. Signs and symptoms of Hennekam syndrome vary widely among affected individuals, even those within the same family. Life expectancy depends on the severity of the disease and may vary from death in infancy to survival into adulthood.
Often the linfangiectasia prevents the flow of lymphatic fluid and can cause rupture of the affected vessels. In the intestines, the breaking of the vessels can lead to accumulation of lymphatic fluid, which interferes with the absorption of nutrients, fats and proteins, which can result in chylous ascites. The linfangiectasia can also affect the kidneys, thyroid gland, pleura, pericardium and skin. For its part, lymphedema syndrome Hennekam usually noticeable at birth and usually affects the face and extremities. Intensely affected children may have a swelling due to fetal hydrops. Lymphedema is usually asymmetric and gradually gets worse over time. On the other hand, the facial features of people affected may include a flattened appearance than half of the face and bridge of the nose, swollen eyelids, hypertelorism, small ears, gingival hypertrophy, craniosynostosis and microcephaly.
Other signs and symptoms of the disease may include intellectual disability that ranges from mild to severe growth retardation, respiratory problems, camptodactilia, cutaneous syndactyly, anemia, polysplenia, kidneys misplaced, genital abnormalities, umbilical hernia, cardiac abnormalities, loss hearing, hirsutism, pectus excavatum, scoliosis and clubfoot.
Hennekam syndrome is due to mutations in genes CCBE1 and FAT4. Mutations in genes FAT4 CCBE1 and represent about 50% of all cases of Hennekam syndrome.
The CCBE1 gene, located on the long arm of chromosome 18 (18q21.32), encodes a protein found in the extracellular matrix and is involved in the formation of the lymphatic system. Specifically, the protein CCBE1 helps differentiation and migration of lymphoblasts that eventually form the epithelium of lymphatic vessels. They have identified at least 13 CCBE1 gene mutations associated with Hennekam syndrome. Most of these genetic mutation changes CCBE1 amino acids in protein, which leads to a change in the three - dimensional form of the protein. The altered protein can not play its role in the formation of the epithelium of lymphatic vessels. A malformed lymphatic system leads to linfangiectasia, lymph vessels prone to rupture, lymphedema, and other characteristics of Hennekam syndrome.
The FAT4 gene, located on the long arm of chromosome 4 (4q28.1), encoding a protein found in most tissues. Protein spans the membrane surrounding the cells so that part of the protein is found on the outside of the cell and part of the protein is inside the cell. Although the exact function of the protein is unknown FAT4 likely be involved in determining cell polarity. Furthermore, it is believed that this protein functions as a tumor suppressor. They have been recognized at least seven mutations in the gene FAT4 that lead to Hennekam syndrome. These genetic mutations reduce activity FAT4 protein, which appears to affect normal development of the lymphatic system. However, the mechanism is unknown. A malformed lymphatic system leads to linfangiectasia, lymph vessels prone to rupture, lymphedema, and other characteristics of Hennekam syndrome.
This disease is inherited in an autosomal recessive pattern, which means that both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.
Tests in IVAMI: in IVAMI perform detection of mutations associated with Hennekam syndrome by complete PCR amplification of the exons of CCBE1 and FAT4, respectively, and subsequent sequencing genes.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).