page_title: L1 syndrome
section_title: Diagnosis
hierarchical_section_title: L1 syndrome / Diagnosis
caption_attribution_description: English: Amniocentesis. See a full animation of this medical topic.
context_page_description: 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 agenesis, spastic paraplegia type 1, MASA syndrome, and X-linked hydrocephalus with stenosis of the aqueduct of Sylvius. It is also called L1CAM syndrome and CRASH syndrome, an acronym for its primary clinical features: corpus callosum hypoplasia, retardation, 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. 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. 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.
context_section_description: A healthcare provider, usually a medical geneticist (a physician with special training in diagnosing and managing genetic disorders) can provide a clinical diagnosis of L1 syndrome by examining a patient and ordering certain imaging studies, however the presence of L1 syndrome can only be confirmed when a molecular diagnosis has been made through genetic testing.
  Often, the diagnostic odyssey for a person with L1 syndrome begins prenatally (before they are born) when prenatal ultrasounds reveal non-specific brain abnormalities, ventriculomegaly, or a non-existent or underdeveloped corpus callosum. Fetuses with X-linked hydrocephalus with stenosis of the aqueduct of Sylvius (HSAS) will typically have hydrocephalus severe enough to be discovered upon routine fetal ultrasound as early as 18–20 weeks gestation. 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. Amniocentesis provides a sample of amniotic fluid that can be used to screen for sequence variants or chromosomal variants, whereas samples obtained through chorionic villus sampling can only be used to detect major chromosomal abnormalities (such as trisomy 21), making chorionic villous sampling less relevant in the context of diagnosing L1 syndrome (which is often caused by sequence variants). Amniocentesis (typically performed between 15–18 weeks of pregnancy) has a 1% risk of complications for mother and fetus, including miscarriage, while chorionic villus sampling (typically performed between 10–12 weeks of pregnancy) has a 2% risk of complications including miscarriage. Mothers carrying a fetus with suspected L1 syndrome will often elect to undergo amniocentesis despite its risk, rather than waiting to pursue lower-risk genetic testing after their child is born, because prenatal diagnostic results can inform considerations to terminate the pregnancy.
  For any child born with multiple physical abnormalities, the first-line diagnostic test is chromosomal microarray.
caption: Amniocentesis being performed to extract amniotic fluid, usually around 4 teaspoons,[30] that can be used as a sample for genetic testing. Amniotic fluid is a watery substance that surrounds the fetus in the womb.[31]
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