Meningocele lateral syndrome ... (Lateral meningocele syndrome) - Gen NOTCH3
Syndrome lateral meningocele is a process that affects the nervous system, bones and muscles, and other body systems. This syndrome is characterized by the presence of abnormalities known as lateral Meningoceles, consisting of protrusions of the meninges through the vertebrae. The bumps are more frequent and are usually larger in the lumbar spine.
Meningoceles associated with this process can damage nerves from the spine to the rest of the body. Damage to the nerves that control bladder function (neurogenic bladder), causes affected individuals suffer a progressive difficulty controlling urine flow. Paresthesia may also occur, stiffness and progressive weakness in the legs, and back pain. Furthermore, this process occurs frequently delayed development of motor skills in childhood, such as sitting and crawling. Intelligence generally not affected. Other characteristics of lateral meningocele syndrome may include hypotonia during childhood, decreased muscle mass and hyperextensibility joints, which can cause dislocations and hernias. They are also frequent bone abnormalities, including scoliosis, merging two or more vertebrae, and unusually vertebrae.
People with lateral meningocele syndrome usually have a particular pattern of facial features that may include high arched eyebrows, Hypertelorism, palpebral fissures down and ptosis. Affected individuals may have hypoplasia of the midface and malar, low - set ears a long philtrum a thin upper lip, cleft palate, micrognathia, thick hair and a bassline hair on the back of the neck. Other signs and symptoms that may occur in the lateral meningocele syndrome include acute and nasally, hearing loss, heart or genitourinary abnormalities, loss of appetite, dysphagia and gastroesophageal reflux or GERD.
This may be due to mutations in the gene NOTCH3 (notch 3), located on the short arm of chromosome 19 (19p13.12) and consisting of a total of 33 exons encoding a receptor of 2321 amino acids with a single transmembrane domain. This gene belongs to the family of the Notch gene consists of four members who play an important role during development, expressed in different tissue types. The products of the genes Notch transmembrane receptors are linked to signaling processes and intercellular communication. The NOTCH3 gene encodes a transmembrane receptor with an extracellular domain containing 34 tandem repeats similar to epidermal growth factor (EGF: Epidermal Grow Factor) factor. Certain ligands, bind to the extracellular end of NOTCH3. This binding elicits intracellular separation NOTCH3 end of the protein, called the intracellular domain NOTCH3, or NICD. The NICD enters the cell nucleus and helps control the transcription of other genes. The NOTCH3 protein plays a key role in the function and survival of vascular smooth muscle cells, which are muscle cells surrounding the blood vessels. This protein is believed to be essential for the maintenance of blood vessels, including those that supply blood to the brain.
They have identified at least six NOTCH3 genetic mutations in people with the syndrome of lateral meningocele. These mutations occur at the end of the gene in a region known as exon 33, and result in a protein with an abnormally NOTCH3 short NICD. The shortened protein lacking the segment which normally causes breakdown after NICD has performed its function in the cell nucleus and is no longer necessary. As a result, the presence of the NICD into the cell is prolonged, and the protein continues to affect the activity of other genes. However, the result of this activity NICD prolonged and its connection with the characteristics of lateral meningocele syndrome are not well understood.
This process is inherited as an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient for the process to be expressed. Most cases are due to new mutations in the gene and occur in people with no history of disease in your family. Occasionally, an affected person inherits the mutation from an affected parent.
Tests in IVAMI: in IVAMI perform detection of mutations associated with syndrome lateral meningocele, by complete PCR amplification of the exons of the gene NOTCH3, 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).