L1 syndrome is a group of mild to severe X-linked recessive disorders that share a common genetic basis. The spectrum of L1 syndrome disorders includes X-linked complicated corpus callosum dysgenesis, spastic paraplegia 1, MASA syndrome, and X-linked hydrocephalus with stenosis of the aqueduct of Sylvius (HSAS). It is also called L1CAM syndrome (for the disorders causative gene) and CRASH syndrome, an acronym for its primary clinical features: corpus callosum hypoplasia, retardation (intellectual disability), adducted thumbs, spasticity, and hydrocephalus.L1 syndrome can be caused by different variants in L1CAM, the gene that provides the information that allows the body to produce L1 cell adhesion molecule (sometimes called the L1 protein). The L1 cell adhesion molecule is a surface protein found on the surface of all neurons. It allows neurons to bind to one another and create synapses (connections where information is passed on from the axons of one neuron to the dendrites and cell body of another). As a result, L1 cell adhesion molecule is essential for the structural development of the brain and contributes to the ability to think, move, and develop memories. The type and severity of L1CAM variant causing L1 syndrome in a particular person is directly related to the severity of symptoms and functional impairment that they experience.There is no cure for L1 syndrome, and prognosis is often poor. Life expectancy for people with L1 syndrome can vary dramatically depending on the severity of the condition, with some dying shortly after birth and others reaching adulthood.
After birth, in the presence of suggestive features (such as macrocephaly), hydrocephalus can be confirmed with noninvasive imaging including head magnetic resonance imaging, computed tomography, or ultrasound showing ventriculomegaly, or direct measurement of intracranial pressure through invasive techniques such as lumbar puncture. Further, the spasticity found in patients with HSAS can be easily demonstrated by examining the deep tendon reflexes and the extensor plantar reflex (which will both be abnormally brisk and strong due to damage to the cortex and internal capsule of the brain). There are various types of genetic testing that can be used to confirm an L1 syndrome diagnosis in a patient. After birth, genetic tests carry a low-risk of physical complications and are minimally-painful: for the patient, the process requires a small amount of blood being drawn from the arm using a needle. However, prenatal genetic testing carries significant risks for both the fetus and mother due to the need to remove genetic material from the fetus while it is still in utero. In order to conduct prenatal genetic testing, the mother and fetus must undergo either amniocentesis (the surgical puncturing of the amniotic sac, which holds the fetus in the womb) or, less frequently, chorionic villus sampling.