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L1 syndrome

Reviewed March 2008

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, mental retardation, 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.

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 striking characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

Where can I find information about treatment for L1 syndrome?

You may find information on treatment or management of L1 syndrome or some of its symptoms in the links below, particularly the links for Gene Reviews, Educational resources, and Patient support.

Where can I find additional information about L1 syndrome?

You may find the following resources about L1 syndrome helpful. These materials are written for the general public.

  • MedlinePlus - Health information
    • Health Topic: Hydrocephalus (http://www.nlm.nih.gov/medlineplus/hydrocephalus.html)
    • Health Topic: Neurologic Diseases (http://www.nlm.nih.gov/medlineplus/neurologicdiseases.html)
    • Health Topic: Neuromuscular disorders (http://www.nlm.nih.gov/medlineplus/neuromusculardisorders.html)
  • Additional NIH Resources - National Institutes of Health
    • National Institute of Neurological Disorders and Stroke: Agenesis of the Corpus Callosum (http://www.ninds.nih.gov/disorders/agenesis/agenesis.htm)
    • National Institute of Neurological Disorders and Stroke: Hereditary Spastic Paraplegia (http://www.ninds.nih.gov/disorders/hereditary_spastic_paraplegia/hereditary_spastic_paraplegia.htm)
    • National Institute of Neurological Disorders and Stroke: Hydrocephalus (http://www.ninds.nih.gov/disorders/hydrocephalus/hydrocephalus.htm)
    • National Institute of Neurological Disorders and Stroke: Seizures and Epliepsy (http://www.ninds.nih.gov/disorders/epilepsy/detail_epilepsy.htm)
  • Educational resources - Information pages
    • Merck Manual of Medical Information, Second Home Edition (http://www.merck.com/mmhe/sec06/ch093/ch093f.html?qt=spastic+paraplegia&alt)
    • Orphanet: MASA syndrome (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=2466)
    • Orphanet: Spastic paraplegia, familial (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=685)
  • Patient support - For patients and families
    • Epilepsy Foundation (http://www.epilepsyfoundation.org/)
    • Family Village: Agenesis of Corpus Callosum (http://www.familyvillage.wisc.edu/lib_agcc.htm)
    • Hydrocephalus Association (http://www.hydroassoc.org/)
    • National Ataxia Foundation (http://www.ataxia.org/)
    • National Organization for Rare Disorders (http://www.rarediseases.org/search/rdbdetail_abstract.html?disname=L1%20Syndrome)
    • Spastic Paraplegia Foundation (http://sp-foundation.org/)
    • University of Kansas Medical Center (http://www.kumc.edu/gec/support/hydrocep.html)
    • WE MOVE (Worldwide Education and Awareness for Movement Disorders) (http://www.wemove.org/)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

  • Gene Reviews - Clinical summary
    • Gene Review: Hereditary Spastic Paraplegia Overview (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=hsp)
    • Gene Review: L1 Syndrome (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=l1cam)
  • Gene Tests - DNA tests ordered by healthcare professionals (http://www.genetests.org/query?testid=226552)
  • ClinicalTrials.gov - Linking patients to medical research (http://clinicaltrials.gov/search/condition=%22l1+syndrome%22+OR+%22genetic+diseases%2C+x-linked%22)
  • PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=PubMed&term=((L1+syndrome[TIAB])+OR+(L1+disease[TIAB])+OR+(L1CAM[TIAB]))+AND+english[la]+AND+human[mh]&orig_db=PubMed&filters=ON&pmfilter_EDatLimit=3600+Days)
  • OMIM - Genetic disorder catalog
    • OMIM: corpus callosum, partial agenesis of, X-linked (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=304100)
    • OMIM: hydrocephalus due to congenital stenosis of aqueduct of Sylvius (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=307000)
    • OMIM: MASA syndrome (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=303350)

What other names do people use for L1 syndrome?

  • CRASH syndrome
  • MASA syndrome
  • SPG1
  • X-linked complicated hereditary spastic paraplegia type 1
  • X-linked corpus callosum agenesis
  • X-linked hydrocephalus with stenosis of the aqueduct of Sylvius (HSAS)

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about L1 syndrome?

  • See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.
  • Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).
  • Submit your question to Ask the Geneticist (http://www.askthegen.org/).

What glossary definitions help with understanding L1 syndrome?

agenesis ; cell ; chromosome ; corpus callosum ; gene ; hydrocephalus ; inheritance ; mental retardation ; mutation ; nerve cell ; nervous system ; neuron ; paraplegia ; protein ; recessive ; seizure ; sex chromosomes ; sign ; spasticity ; stenosis ; symptom ; synapse ; syndrome ; tissue ; trait ; X-linked recessive

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

References
  • Finckh U, Schröder J, Ressler B, Veske A, Gal A. Spectrum and detection rate of L1CAM mutations in isolated and familial cases with clinically suspected L1-disease. Am J Med Genet. 2000 May 1;92(1):40-6. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=10797421)
  • Hübner CA, Utermann B, Tinschert S, Krüger G, Ressler B, Steglich C, Schinzel A, Gal A. Intronic mutations in the L1CAM gene may cause X-linked hydrocephalus by aberrant splicing. Hum Mutat. 2004 May;23(5):526. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=15108295)
  • Kanemura Y, Okamoto N, Sakamoto H, Shofuda T, Kamiguchi H, Yamasaki M. Molecular mechanisms and neuroimaging criteria for severe L1 syndrome with X-linked hydrocephalus. J Neurosurg. 2006 Nov;105(5 Suppl):403-12. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=17328266)
  • Reid E. Science in motion: common molecular pathological themes emerge in the hereditary spastic paraplegias. J Med Genet. 2003 Feb;40(2):81-6. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=12566514)
  • Soderblom C, Blackstone C. Traffic accidents: molecular genetic insights into the pathogenesis of the hereditary spastic paraplegias. Pharmacol Ther. 2006 Jan;109(1-2):42-56. Epub 2005 Jul 7. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16005518)
  • Weller S, Gärtner J. Genetic and clinical aspects of X-linked hydrocephalus (L1 disease): Mutations in the L1CAM gene. Hum Mutat. 2001;18(1):1-12. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=11438988)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: March 2008
Published: January 12, 2009