Hydrocephalus, X-linked (L1CAM)
Pathogenic variants in L1CAM cause a range of hydrocephalus disorders and are inherited in an X-linked manner. The most severe disease associated with L1CAM pathogenic variants is hydrocephalus due to congenital stenosis of the aqueduct of Sylvius (HSAS). This disease is characterized by brain malformations, severe hydrocephalus, spasticity, and adducted thumbs. Individuals with HSAS often have severe intellectual disability and seizures. HSAS usually has a prenatal onset that can result in stillbirth or death during early infancy. Some patients with L1CAM pathogenic variants have MASA syndrome (an acronym standing for mental retardation, adducted thumbs, shuffling gait, and aphasia), spastic paraplegia 1, or agenesis of the corpus callosum. Truncating mutations in L1CAM are more likely to cause a more severe clinical presentation (such as more severe hydrocephalus, intellectual disability, or early death); however, the phenotype can vary greatly among individuals with the same pathogenic variant, even in the same family.
For information about carrier frequency and residual risk, please see the residual risk table.