L1 syndrome describes a group of conditions that primarily affect the nervous system and occur almost exclusively in males. These conditions vary in severity and include, from most severe to least, X-linked hydrocephalus with stenosis of the aqueduct of Sylvius (HSAS), MASA syndrome, spastic paraplegia type 1, and X-linked complicated corpus callosum agenesis.

L1 syndrome is caused by mutations in the L1CAM gene. The L1CAM gene provides instructions for producing the L1 cell adhesion molecule protein (shortened to L1 protein), which is found throughout the nervous system. This protein is present on the surface of nerve cells (neurons), where it attaches (binds) to proteins on neighboring neurons to help the cells stick to one another (cell-cell adhesion). The L1 protein plays a role in numerous functions of neurons that contribute to brain development, thinking ability, memory, and movement.

The prevalence of L1 syndrome overall is unknown; however, HSAS is estimated to affect 1 in 30,000 males.

This condition is inherited in an X-linked pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes in each cell. In males, who have only one X chromosome, a mutation in the only copy of the gene in each cell is sufficient to cause the condition. In females, who have two copies of the X chromosome, one altered copy of the gene in each cell can lead to less severe features of the condition or may cause no signs or symptoms at all. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

Published Date: June 10, 2021
Published By: National Institutes of Health