Landau-Kleffner syndrome

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Rare Pediatrics News

Disease Profile

US Estimated

Europe Estimated

Age of onset

Childhood

ICD-10

F80.3

Inheritance

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.

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

Not applicable

Other names (AKA)

Acquired aphasia with convulsive disorder; LKS; Acquired epileptiform aphasia;

Summary

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]

Symptoms

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]

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.

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

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Cause

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]

Diagnosis

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]

Treatment

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]

Related diseases

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.

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.

Organizations

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

Epilepsy Action
New Anstey House Gate Way Drive
Yeadon, LEEDS LS19 7XY
United Kingdom
Telephone: 0113 210 8800 (UK) or +44 (0)113 210 8800 (international)
Fax: 0113 391 0300 (UK) or +44 (0)113 391 0300 (international)
E-mail: epilepsy@epilepsy.org.uk
Website: https://www.epilepsy.org.uk/

Organizations Providing General Support

Epilepsy Foundation
8301 Professional Place East
Suite 230
Landover, MD 20785
Toll-free: 800-332-1000 (24/7 Helpline)
Telephone: +1-301-459-3700
Fax: +1-301-577-2684
E-mail: contactus@efa.org
Website: https://www.epilepsy.com/
en Español 1-866-748-8008
National Aphasia Association (NAA)
P.O. Box 87
Scarsdale, NY 10583
E-mail: naa@aphasia.org
Website: https://www.aphasia.org/

Learn more

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

MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
Genetics Home Reference (GHR) contains information on Landau-Kleffner syndrome. This website is maintained by the National Library of Medicine.
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.

References

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.
Loddenkemper T and Sanchez Fernandez I. Landau-Kleffner syndrome. Orphanet. April 2014; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=98818.
Epilepsy-aphasia spectrum. Genetics Home Reference. November 2016; https://ghr.nlm.nih.gov/condition/epilepsy-aphasia-spectrum.
Mantovani JF. Landau Kleffner Syndrome. National Organization for Rare Disorders (NORD). 2015; https://rarediseases.org/rare-diseases/landau-kleffner-syndrome/.
Neiman ES and Seyffert M. Acquired Epileptic Aphasia. Medscape. December 9, 2015; https://emedicine.medscape.com/article/1176568.
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.
Myers KA and Scheffer IE. GRIN2A-Related Speech Disorders and Epilepsy. GeneReviews. September 29, 2016; https://www.ncbi.nlm.nih.gov/books/NBK385627/.
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. https://onlinelibrary.wiley.com/doi/10.1111/epi.12645/full.
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. https://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.

Rare Pediatrics News

Rare Pediatrics News

Rare Pediatrics News

Childhood

F80.3

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.

X-linked dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

X-linked recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

Not applicable

Other names (AKA)

Categories

Summary

Symptoms

Cause

Diagnosis

Treatment

Related diseases

Organizations

Organizations Supporting this Disease

Organizations Providing General Support

Learn more

Where to Start

In-Depth Information

References

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.