L1 syndrome is a group of conditions that affect the nervous system. The main symptom is too much fluid around the brain, called hydrocephalus.
People with L1 syndrome might also have stiff and tight muscles in their legs, making it hard to walk. Other symptoms include intellectual disability, trouble speaking, and brain abnormalities. Some may have thumbs that are always bent inward (adducted thumbs). The symptoms can vary a lot, even among people in the same family. L1 syndrome includes a range of related disorders:
X-Linked Hydrocephalus with Stenosis of the Aqueduct of Sylvius (HSAS): HSAS is the most severe form of L1 syndrome. Symptoms often show up at or before birth and mainly affect people assigned male at birth. Almost everyone with HSAS has too much fluid around the brain and other brain issues. They usually have adducted thumbs and tight muscles. Severe intellectual disability is also common.
MASA Syndrome: MASA stands for Mental retardation (intellectual disability), Aphasia (speech problems), Spastic paraplegia (stiff legs), Adducted thumbs. People with MASA syndrome may have brain abnormalities, intellectual disability, tight muscles, and adducted thumbs, but the symptoms are usually less severe than in HSAS.
X-Linked Complicated Corpus Callosum Agenesis: this condition typically includes a thin or missing part of the brain that connects the two sides (agenesis of the corpus callosum), tight muscles, and mild to moderate intellectual disability.
There is no cure for L1 syndrome, but treatment focuses on managing symptoms. A tube (shunt) can help drain the fluid around the brain. A splint may help with adducted thumbs, and physical therapy and medications can help with tight muscles. People with intellectual disabilities may benefit from early intervention and special education. Those with L1 syndrome should work with a team of specialists, including surgeons, physical and occupational therapists, and neurologists.
These disorders are caused by pathogenic variants in the L1CAM gene and exhibit X-linked recessive inheritance. This means that one pathogenic variant is enough to cause the disease in both individuals assigned male at birth (who have one X chromosome and one Y chromosome) and individuals assigned female at birth (who have two X chromosomes) may experience symptoms depending on how many copies of the X chromosome that has the pathogenic variant are turned on in the cells.
While female carriers are unlikely to be affected by L1 syndrome, clasped thumbs and mild intellectual disability have been reported in a few female (XX) individuals with mutations in the L1CAM gene.
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Written August 2024
