L1 syndrome

What is L1 syndrome?

L1 syndrome includes a group of inherited conditions that impact the nervous system. All conditions associated with L1 syndrome are caused by harmful genetic changes (variants) in the L1CAM gene. The primary symptom of L1 syndrome is excess fluid around the brain (hydrocephalus). Individuals may also have other issues like stiff and tight muscles (spasticity) in the legs, making walking hard. Other symptoms include intellectual disability, difficulty with speech, and brain abnormalities (agenesis of the corpus callosum). Some individuals may have clasped (adducted) thumbs. The symptoms of L1 syndrome can vary significantly between affected individuals, even those within the same family. L1 syndrome is an X-linked disease, meaning that people assigned male at birth (XY) usually have more severe symptoms than those assigned female (XX).

L1 syndrome is a spectrum of related disorders that are grouped into the following conditions:

X-linked hydrocephalus with stenosis of the aqueduct of Sylvius (HSAS)

HSAS is the most severe presentation of L1 syndrome. The symptoms are often present at or before birth. HSAS primarily affects people assigned male at birth (XY). Almost all individuals with this form will have excess fluid around the brain and brain abnormalities (agenesis of the corpus callosum). Individuals typically have clasped (adducted) thumbs and stiff and tight muscles. Severe intellectual disability is common in HSAS.

MASA syndrome

MASA syndrome stands for "Mental retardation (intellectual disability), Aphasia (speech problems), Spastic paraplegia (stiffness in the legs), Adducted (clasped) thumbs." Many individuals will have some brain abnormalities, intellectual disability, stiff and tight muscles, and clasped thumbs, but they are usually less severely affected than individuals with HSAS.

X-linked complicated corpus callosum agenesis

Symptoms typically include thinning or absence of the tissue that connects the left and right side of the brain (agenesis of the corpus callosum), stiff and tight muscles of the limbs, and mild to moderate intellectual disability.

Additional considerations for carriers

Carriers are unlikely to be affected by L1 syndrome; however, clasped thumbs and mild intellectual disability have been reported in a few female (XX) individuals with harmful changes in the L1CAM gene.

How common is L1 syndrome?

L1 syndrome is estimated to affect 1 in 30,000 male births.

How is L1 syndrome treated?

There is no cure for L1 syndrome. Treatment is based on the symptoms the individual is experiencing. A tube (shunt) can drain the fluid around the brain. A splint may help with clasped thumbs, and physical therapy and medications can help treat stiff and tight muscles. Individuals with intellectual disability may benefit from early intervention and educational support. All individuals with L1 syndrome will benefit from working with a team of specialists that includes surgeons, physical and occupational therapists, and neurologists.

What is the prognosis for a person with L1 syndrome?

The prognosis depends on the severity of symptoms. Severe cases of hydrocephalus may result in stillbirth or pass away shortly after birth, while less severe cases may have a normal lifespan. Intellectual disability can range from mild to severe and some individuals may need lifelong support.