Silver-Russell syndrome ... Silver-Russell syndrome) - Gen BSCL2.
Silver syndrome-Russel belongs to a group of genetic alterations known as hereditary spastic paraplegia. These changes are characterized by spasticity and often paraplegia. Hereditary spastic paraplegia the fall into two types: pure and complex. Both involve the lower extremities. Complex types can also involve the upper limbs, although to a lesser degree. In addition, complex types can affect the brain and parts of the nervous system involved in muscle movement and sensation. The Silver-Russell syndrome is part of the complex of hereditary spastic paraplegia type.
This syndrome is usually characterized by muscle weakness in the hands. These muscles are worn, resulting in abnormal positioning of the thumb and difficulty using the fingers and hands for tasks such as writing. People with this syndrome often have pes cavus and spasticity in the legs. Signs and symptoms usually begin in late childhood, but can start at any time from early childhood to late adulthood. Muscle problems associated with the syndrome slowly worsen with age, although affected individuals may remain active throughout life.
This process is due to mutations in BSCL2, located on the long arm of chromosome 11 (11q13), encoding the protein seipina, whose function is unknown. The BSCL2 gene is active in cells throughout the body, particularly in motor neurons and in brain cells. Within cells, the seipina is in the membrane of the endoplasmic reticulum, involved in the processing and intracellular transport of proteins.
They found at least two mutations in the gene BSCL2, causing the Silver-Russell syndrome of including N88S and S90L mutations. Mutations cause muscle weakness and spasticity in the legs. These mutations probably result from misfolded seipina molecules that build up inside neurons, leading to damage and cell death.
This syndrome is inherited as an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient to cause the disorder. In these cases, the affected person inherits the mutation from an affected parent. However, some people who inherit the altered gene never develop the disease own characteristics. It is not clear why some people with a mutated gene develop the disease and others do not. Rarely, the syndrome is caused by new mutations in the gene and occur in people with no history of disease in your family.
Tests in IVAMI: in IVAMI perform detection of mutations associated with syndrome Silver-Russell, by complete PCR amplification of exons BSCL2 gene, and subsequent sequencing.
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).