or can be also referred as L1 syndrome. This includes disorders such as HSAS, MASA syndrome, agenesis of the corpus callosum and spastic paraplegia. Lower limb spasticity, mental retardation, hydrocephalus and flexion deformity of the thumbs are some of the symptoms expressed mostly in male individuals who suffer from this condition. Although the pathological mechanisms leading to L1 syndrome are still unknown, about 200 mutations of the L1CAM gene have been identified and then associated with the syndrom. These mutations mostly affect structurally important key residues in the extracellular region of L1 causing alterations in the protein binding properties, which correlate to the impairment of neuronal physiological mechanisms such as cell adhesion or specific interacting with other molecules. Ankyrin interaction with L1CAM is an example of a protein binding that fails in CRASH patients due to a mutation that causes leucine and histidine to replace serine and tyrosine respectively, in the SFIGQY motif, where ankyrin should be bound in the L1CAM family cytoplasmic terminus. Ankyrin-L1CAM interaction is involved in the growth cone initiation, consequently, a failure in this interaction causes neurites to not reach synaptic target. Furthermore, evidence shows there is a correlation between fetal alcohol spectrum disorder and L1 protein since ethanol inhibits L1-mediated adhesion and neurite outgrowth. Hirschsprung's disease has also been linked to a L1CAM malfunction. Transcription and synthesis The gene that regulates L1CAM transcription is found in chromosome X. The L1CAM gene is 24,657 bp in length, and is made up of 28 exons. The alternative splicing of this gene leads to multiple transcript variants (there are 7 different transcripts of the gene), including some that have an alternate exon that is considered to be specific to neurons. L1 transcription is known to take place in human fetal brain and in neuroblastoma and retinoblastoma cell lines. L1 is also expressed in the rhabdomyosarcoma cell lines RD and A-204. Two forms of L1 can be found in humans, with the difference that one has a 12-bp cytoplasmic segment and the other lacks of it. The regulation of L1CAM expression in transcription is not fully comprehended. Two sites were verified in endometrial carcinoma cell lines and seem to be used in a specific manner depending on the cell type. There are two transcription beginning sites, located in two different exons (in front of a non-translated exon 0 and next to the first protein-coding exon 1). SLUG (SNAI2), a