National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Landau-Kleffner syndrome


Other Names:
Acquired aphasia with convulsive disorder; LKS; Acquired epileptiform aphasia; Acquired aphasia with convulsive disorder; LKS; Acquired epileptiform aphasia; Acquired epileptic aphasia See More
Categories:
Landau-Kleffner syndrome (LKS) is a rare neurological syndrome characterized by the sudden or gradual development of aphasia (the inability to understand or express language) and recurrent seizures (epilepsy). Children with LKS typically develop normally until signs and symptoms of the syndrome begin to develop between age 2 and 8 years.[1][2] Males are more  often affected by LKS than females.[1] 

In about 20% of people with LKS, mutations (changes) in the GRIN2A gene have been identified. The syndrome is inherited in an autosomal dominant manner. In other cases, the syndrome may be caused by changes to other unidentified genes.[3] LKS is diagnosed when a doctor sees clinical features that are consistent with the syndrome such as a loss of speech and an electroencephalogram (EEG) that shows specific kinds of seizure activity. Genetic testing can be used to confirm if there is a mutation in GRIN2A, but this testing is not done routinely.[2]

Treatment for LKS usually consists of medications such as anticonvulsants and corticosteroids to help prevent seizures. Speech therapy should also be started promptly in order to ensure the best long-term outlook for children with LKS.[2]
Last updated: 8/11/2017
Landau-Kleffner syndrome (LKS) is characterized by the sudden or gradual development of aphasia (the inability to understand or express language). Children affected with LKS have developed normally until signs and symptoms begin between the ages of 2 and 8.[1][2] This syndrome is also characterized by an abnormal electroencephalogram (EEG), especially during sleep.[4] About 70% of children with LKS have seizures.[3] The seizures associated with LKS are known as complex partial, generalized clonic, and atypical absence seizures and are generally easy to control with medications. 

Some children with Landau-Kleffner syndrome may develop behavioral problems including hyperactivity, attention deficits, temper outbursts, impulsivity, and/or withdrawn behaviors.[4] Some children with Landau Kleffner syndrome may also have intellectual disability.[3] As researchers continue to learn more about LKS, it seems that there may be a wider variety of signs and symptoms associated with this syndrome than originally thought. There may be a variability of symptoms associated with LKS even within the same family.[5]
Last updated: 8/11/2017

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms Other Names
Learn More:
HPO ID
5%-29% of people have these symptoms
Global developmental delay 0001263
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation
[ more ] 		0001249
Percent of people who have these symptoms is not available through HPO
Agnosia 0010524
Aphasia
Difficulty finding words
Losing words
Loss of words
[ more ] 		0002381
Attention deficit hyperactivity disorder
Attention deficit
Attention deficit disorder
Attention deficit-hyperactivity disorder
Attention deficits
Childhood attention deficit/hyperactivity disorder
[ more ] 		0007018
Autosomal dominant inheritance 0000006
Behavioral abnormality
Behavioral changes
Behavioral disorders
Behavioral disturbances
Behavioral problems
Behavioral/psychiatric abnormalities
Behavioural/Psychiatric abnormality
Psychiatric disorders
Psychiatric disturbances
[ more ] 		0000708
Delayed speech and language development
Deficiency of speech development
Delayed language development
Delayed speech
Delayed speech acquisition
Delayed speech development
Impaired speech and language development
Impaired speech development
Language delay
Language delayed
Language development deficit
Late-onset speech development
Poor language development
Speech and language delay
Speech and language difficulties
Speech delay
[ more ] 		0000750
Dysphasia 0002357
EEG with centrotemporal focal spike waves 0012557
Incomplete penetrance 0003829
Seizure 0001250
Speech apraxia 0011098
Variable expressivity 0003828
Showing of 14 |
Last updated: 7/1/2020
In some cases, Landau-Kleffner syndrome is thought to be caused by mutations(changes) in the GRIN2A  gene. This gene provides instructions to the body to make a protein that sends signals to the nerve cells (neurons) in the brain. When these signals are not being transmitted properly, they may affect the ability to understand or express language.[3] These signals may also cause receptors in the brain to be turned on abnormally, resulting in seizures.[3] It has been proposed that the seizures associated with LKS may cause damage to the parts of the brain responsible for speech, but this hypothesis has not been confirmed.[5]

In about 80% of people diagnosed with LKS, no mutation is found in the GRIN2A gene. In these cases, it is thought that LKS could be caused by mutations in other genes or an interaction between genes and the environment.[3] It has also been proposed that in some cases LKS may be the result of an autoimmune response that occurs when the body attacks itself as if it were an infection.[5]  
Last updated: 8/11/2017
In cases where Landau-Kleffner syndrome is caused by mutations to GRIN2A, it is inherited in an autosomal dominant manner.[3] This means that if one copy of the GRIN2A gene is changed, a person will have symptoms of the syndrome. We inherit one copy of each gene from our mother and the other from our father. 

When a person with Landau-Kleffner syndrome has children, each child has a 50% (1 in 2) chance to inherit the same gene change that causes the syndrome. However, LKS reportedly shows reduced penetrance.[6] This means that not every person with a disease-causing mutation will have features of the syndrome. Therefore, it is possible for this syndrome to appear to “skip” generations. If a person with LKS has a child with the gene change but no features of the syndrome, when this person goes on to have children, he or she may have features of LKS. 

Landau-Kleffner syndrome also shows variable expressivity.[5] This means that not all affected people will have the same signs and symptoms, and some people may be more severely affected than others.

In some cases, a mutation that causes an autosomal dominant syndrome is inherited from a parent with the mutation. In other cases, autosomal dominant syndromes are due to new mutations that occur for the first time (de novo) in an affected person. 

In cases where Landau-Kleffner syndrome is not caused by a mutation in GRIN2A, it is not known if the syndrome may be inherited. If LKS is caused by a mutation in another gene, this mutation can be passed from parent to child.
Last updated: 8/11/2017
Landau-Kleffner syndrome (LKS) is diagnosed based on clinical features and the results of an electroencephalogram (EEG). An EEG is a recording of the electrical activity of the brain, and this can be completed when a child is asleep or awake. Children with LKS have abnormal electrical brain activity on both the left and right side of the brain.[1] Brain MRI may be used to confirm that there is not another underlying cause of the symptoms. Audiometry (hearing study) may additionally be useful to confirm that the loss of language is not due to trouble with hearing.[7] In some cases, LKS is originally misdiagnosed as autism, pervasive developmental disorder, hearing impairment, learning disability, auditory/verbal processing disorder, attention deficit disorder, intellectual disability, childhood schizophrenia, or emotional/behavioral problems.[3]

Because a single underlying genetic cause has not been identified for all individuals with LKS, routine genetic testing is not completed at all centers. Researchers additionally suspect that mutations within the RELN, BSN, and EPHB2  genes might be involved with the symptoms of LKS.[4][8] 
Last updated: 8/11/2017
The treatment for Landau-Kleffner syndrome may vary depending on the specific symptoms present in each person. Children who have seizures may be prescribed anticonvulsant medications and corticosteroids may be recommended.[1] In some cases, immunotherapy may improve speech and seizures.[9] In rare cases in which other treatment options for seizures have not been successful, a surgery called multiple subpial transection may help to relieve seizures.[2]

Speech therapy should be initiated as soon as possible to help children regain speech.[1] Speech therapists may also recommend helping children learn sign language to help them find new ways to communicate.[4] Special education may also be necessary in some cases.[4]
Last updated: 8/11/2017
The long-term outlook for people affected by Landau-Kleffner syndrome may depend on the age that a child started showing symptoms of the syndrome and the severity of seizures. The prognosis for the disorder is best when a child started showing symptoms after age 6 years, and therapies are usually most effective in these cases.[1]

In most cases, seizures are well-controlled with medication, and they typically disappear completely by adulthood.[1] While speech therapy improves the language abilities of most people with LKS, most children do not regain complete language ability.[2] Improvement of language in children with LKS may require months or years of therapy.[1]
Last updated: 8/11/2017

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
The differential diagnosis includes any epileptic syndrome with sleep potentiation of epileptiform activity such as continuous spikes and waves during sleep, Panayiotopoulos and Gastaut types of benign childhood occipital epilepsy and rolandic epilepsy (see these terms). It is important to rule out a hearing defect and/or autism that may present initially in a similar way.
Visit the Orphanet disease page for more information.

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to Landau-Kleffner syndrome. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on Landau-Kleffner syndrome. This website is maintained by the National Library of Medicine.
  • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
  • The National Institute of Neurological Disorders and Stroke (NINDS) collects and disseminates research information related to neurological disorders. Click on the link to view information on this topic.
  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

  • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Landau-Kleffner syndrome. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

  • What types of symptoms are seen in people with Landau-Kleffner syndrome? See answer


  1. Landau-Kleffner Syndrome Information Page. National Institute of Neurological Disorders and Stroke. https://www.ninds.nih.gov/Disorders/All-Disorders/Landau-Kleffner-Syndrome-Information-Page. Accessed 8/6/2017.
  2. Loddenkemper T and Sanchez Fernandez I. Landau-Kleffner syndrome. Orphanet. April 2014; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=98818.
  3. Epilepsy-aphasia spectrum. Genetics Home Reference. November 2016; https://ghr.nlm.nih.gov/condition/epilepsy-aphasia-spectrum.
  4. Mantovani JF. Landau Kleffner Syndrome. National Organization for Rare Disorders (NORD). 2015; https://rarediseases.org/rare-diseases/landau-kleffner-syndrome/.
  5. Neiman ES and Seyffert M. Acquired Epileptic Aphasia. Medscape. December 9, 2015; http://emedicine.medscape.com/article/1176568.
  6. Epilepsy, Focal, With Speech Disorder And Or Without Mental Retardation; FESD. Online Mendelian Inheritance in Man. May 11, 2017; https://www.omim.org/entry/245570.
  7. Myers KA and Scheffer IE. GRIN2A-Related Speech Disorders and Epilepsy. GeneReviews. September 29, 2016; https://www.ncbi.nlm.nih.gov/books/NBK385627/.
  8. Conroy J, McGettigan PA, McCreary D, Shah N, Collins K, Parry-Fielder B, Moran M, Hanrahan D, Deonna TW, Korff CM, Webb D, Ennis S, Lynch SA, King MD. Towards the identification of a genetic basis for Landau-Kleffner syndrome. Epilepsia. Jun 2014; 55(6):858-65. http://onlinelibrary.wiley.com/doi/10.1111/epi.12645/full.
  9. Fainberg N, Harper A, Tchapyjnikov D, and Mikati MA. Response to immunotherapy in a patient with Landau-Kleffner syndrome and GRIN2A mutation. Epileptic Disorders. March 2016; 18(1):97-100. http://www.jle.com/fr/revues/epd/e-docs/response_to_immunotherapy_in_a_patient_with_landau_kleffner_syndrome_and_grin2a_mutation_306244/article.phtml?tab=texte.