CRASH syndrome ..., (Hydrocephalus X - linked syndrome MASA, spastic paraplegia Family Type 1, Agenesis of Corpus Callosum , X - linked syndrome L1) CRASH Syndrome (X-linked hydrocephalus syndrome, MASA syndrome, Spastic paraplegia type 1 , X-linked the corpus callosum agenesis, L1 Syndrome) - Gen L1CAM
Hydrocephalus X - linked, MASA syndrome (Mental retardation, aplasia, Shuffling gait, and adducted thumbs), certain forms of spastic paraplegia X - linked familial spastic -Paraplejia 1- and agenesis of the corpus callosum due to mutations in the gene of the cell adhesion molecule L1 neural. Therefore, these syndromes was recently classified as CRASH syndrome (also called Syndrome L1), an acronym for Corpus callosum hypoplasia, Retardation, adducted thumbs, Spasticity and Hydrocephalus -Hipoplasia the corpus callosum, mental retardation, thumbs adducted, spasticity and Hydrocephalus - main clinical manifestations characterized by.
This process is due to mutations in the gene L1CAM, located on the long arm of chromosome X (Xq28). The encoded protein, L1, is a cell adhesion molecule (CAM) superfamily member of immunoglobulins (Ig). This cell adhesion molecule plays a key role in the development of the central nervous system (CNS), in the formation of the protective myelin sheath surrounding some neurons, and in the formation of synaptic junctions between nerve cells. Structurally is a transmembrane glycoprotein of 200 kDa with six Ig-like domains followed by five fibronectin type III domains, a small transmembrane region and a cytoplasmic domain of 114 amino acids. Generally, L1 proteins are expressed on the surface of the long neuronal axons and nerve growth cones. It is also expressed in Schwann cells and in other cell types, generally originating from the neural crest.
They described about 200 L1CAM gene mutations that result in CRASH syndrome or syndrome L1. These mutations change the structure of the L1 protein or interrupt coding. There is a correlation between the type of mutation in the gene L1CAM and severity of the disease. Mutations causing truncations in the extracellular domain of the L1 protein are more likely to cause severe hydrocephalus, severe mental retardation and early death that point mutations in the extracellular domain or mutations affecting only the cytoplasmic domain of the protein. Although less severe than truncations in the extracellular domain, point mutations in this domain cause severe neurological problems that mutations that affect only the cytoplasmic domain, as the latter results in proteins that retain the ability to exercise their extracellular functions and cell adhesion, while the former can keep only some of its functions and partially.
This process is inherited as a recessive X - linked pattern The related gene is on the X chromosome, one of the two sex chromosomes. In males, who have only one X chromosome alteration is enough to express the disease. In women, who have two X chromosomes, mutations must occur in both to manifest the disease. For this reason, the disease is more common in men and, on the other hand, is very rare in women. A feature of the inheritance X - linked diseases, is that the father does not transmit the disease to their children.
Tests in IVAMI: in IVAMI perform detection of mutations associated consÃndrome CRASH by complete PCR amplification of the exons of the gene L1CAM 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).