What is L1 Syndrome?

July 10, 2014

What is L1 syndrome?

L1 syndrome is an inherited disorder that primarily affects the nervous system. L1 syndrome involves a variety of features that were once thought to be distinct disorders, but are now considered to be part of the same syndrome.

The most common characteristics of L1 syndrome are muscle stiffness (spasticity) of the lower limbs, intellectual disability, increased fluid in the center of the brain (hydrocephalus), and thumbs bent toward the palm (adducted thumbs). People with L1 syndrome can also have difficulty speaking (aphasia), seizures, and underdeveloped or absent tissue connecting the left and right halves of the brain (agenesis of the corpus callosum).

The symptoms of L1 syndrome vary widely among affected individuals, even among members of the same family. Because this disorder involves spasticity of the lower limbs, L1 syndrome is sometimes referred to as spastic paraplegia type 1 (SPG1).

How common is L1 syndrome?

L1 syndrome is estimated to occur in 1 in 25,000 to 60,000 males. Females are rarely affected by this condition.

What genes are related to L1 syndrome?

L1 syndrome is caused by mutations in the L1CAM gene. The L1CAM gene provides instructions for producing the L1 protein, which is found throughout the nervous system on the surface of nerve cells (neurons). The L1 protein plays a role in the development and organization of neurons, the formation of the protective sheath (myelin) that surrounds certain neurons, and the formation of junctions between nerve cells (synapses), where cell-to-cell communication occurs. Mutations in the L1 protein can interfere with these developmental processes. Research suggests that a disruption in the development and function of neurons causes the signs and symptoms of L1 syndrome.

Read more about the L1CAM gene.

How do people inherit L1 syndrome?

This condition is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

What other names do people use for L1 syndrome?
  • CRASH syndrome
  • MASA syndrome
  • spastic paraplegia 1
  • SPG1
  • X-linked complicated hereditary spastic paraplegia type 1
  • X-linked corpus callosum agenesis
  • X-linked hydrocephalus syndrome
  • X-linked hydrocephalus with stenosis of the aqueduct of Sylvius (HSAS)
What does it mean if a disorder seems to run in my family?

A particular disorder might be described as “running in a family” if more than one person in the family has the condition. Some disorders that affect multiple family members are caused by gene mutations, which can be inherited (passed down from parent to child). Other conditions that appear to run in families are not caused by mutations in single genes. Instead, environmental factors such as dietary habits or a combination of genetic and environmental factors are responsible for these disorders.

It is not always easy to determine whether a condition in a family is inherited. A genetics professional can use a person’s family history (a record of health information about a person’s immediate and extended family) to help determine whether a disorder has a genetic component. He or she will ask about the health of people from several generations of the family, usually first-, second-, and third-degree relatives.

Degrees of relationship
Degrees of relationship Examples
First-degree relatives Parents, children, brothers, and sisters
Second-degree relatives Grandparents, aunts and uncles, nieces and nephews, and grandchildren
Third-degree relatives First cousin

Some disorders are seen in more than one generation of a family.

Some disorders are seen in more than one generation of a family.

All info was acquired from

Thanks to Tracy Felix for this story. Her son has L1 Syndrome, which she blogs about on her site:  You can also read more about L1 on their Facebook:

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