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Condition report · Neurological

L1 Syndrome

Whole genome sequencing reads the L1CAM gene on the X chromosome for changes that cause L1 syndrome, a condition that mainly affects boys and can include hydrocephalus, intellectual disability and stiff legs.

A condition report looks for rare variants known to cause the conditions it covers.

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About this condition

An X-linked condition mainly affecting boys, causing a range of brain development differences including hydrocephalus, intellectual disability, stiff legs and inward-bent thumbs. It is caused by changes in the L1CAM gene, which helps nerve cells connect.

L1 syndrome is a group of brain development conditions that mainly affect boys. The spectrum ranges from severe hydrocephalus, a build-up of fluid in the brain that can be present before birth, to milder learning and walking difficulties. Affected boys can have intellectual disability, leg spasticity and thumbs bent towards the palm. Different features can appear within the same family.

The condition is caused by changes in L1CAM, which is on the X chromosome. The gene encodes an adhesion molecule that nerve cells need in order to migrate and to grow their fibres. Males with one changed copy are affected, while carrier females usually have no or mild features. The spectrum includes X-linked hydrocephalus with stenosis of the aqueduct of Sylvius, MASA syndrome and agenesis of the corpus callosum.

L1 syndrome is inherited in an X-linked way. Treatment depends on the features. Shunting of fluid is performed when hydrocephalus needs it, physiotherapy helps with spasticity, and educational support is given for developmental delay. Female relatives can have carrier testing, and genetic counselling covers the 1 in 2 chance that a carrier mother's sons are affected.

The condition we analyse

X-linked recessive

Caused by changes in L1CAM on the X chromosome, which encodes an adhesion molecule needed for nerve cell migration and growth of nerve fibres. Males with one changed copy are affected; carrier females usually have no or mild features.

Signs and symptoms

The spectrum includes X-linked hydrocephalus with narrowing of the brain's aqueduct, MASA syndrome (intellectual disability, aphasia, shuffling gait and adducted thumbs), spastic paraplegia and agenesis of the corpus callosum. Affected males can have intellectual disability, leg spasticity and thumbs held across the palm. Severity ranges from severe hydrocephalus before birth to milder learning and walking difficulties.

What a diagnosis changes

Neurosurgical treatment of hydrocephalus when needed, with physiotherapy for spasticity and developmental and educational support. Female relatives can have carrier testing, and genetic counselling covers the 1 in 2 chance that a carrier mother's sons are affected.

Genes analysed

Also known as

corpus callosum hypoplasia-retardation-adducted thumbs-spasticity-hydrocephalus syndrome; CRASH syndrome; L1CAM syndrome

Includes 4 related subtypes ↓
  • MASA syndrome
  • X-linked complicated corpus callosum dysgenesis
  • X-linked complicated spastic paraplegia type 1
  • X-linked hydrocephalus with stenosis of the aqueduct of Sylvius
MONDO:0017140Orphanet 275543MedGen 1830362Sources: [1][2][3]

Why whole genome sequencing

L1 syndrome is passed down through the X chromosome, so a gene result can guide testing in female relatives.

Treating fluid on the brain

Neurosurgical treatment of hydrocephalus is used when it is needed, with a multidisciplinary team. Regular neurological checks monitor hydrocephalus, development and spasticity. A splint may help reduce thumb adduction, although surgery is not generally indicated.

Carrier mothers and female relatives

If a mother carries an L1CAM change, each of her sons has a 1 in 2 chance of being affected. Female relatives can be offered carrier testing. A diagnosis in a female is unusual but not impossible, and genetic counselling explains the pattern.

References

  1. Stumpel C, Vos YJ, 2004. L1 Syndrome. GeneReviews
  2. L1 syndrome. MedlinePlus Genetics
  3. L1CAM gene. MedlinePlus Genetics

Other neurological conditions

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