Landau-Kleffner syndrome

Alternate names

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

Definition

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).

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.
• These signals may also cause receptors in the brain to be turned on abnormally, resulting in seizures.
• 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.
• 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.
• 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.

Inheritance

Autosomal dominant pattern, a 50/50 chance.

• In cases where Landau-Kleffner syndrome is caused by mutations to GRIN2A, it is inherited in an autosomal dominant manner.
• 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.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.
• 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.

Onset

Children affected with LKS have developed normally until signs and symptoms begin between the ages of 2 and 8.

Signs and symptoms

• Landau-Kleffner syndrome (LKS) is characterized by the sudden or gradual development of aphasia (the inability to understand or express language).
• This syndrome is also characterized by an abnormal electroencephalogram (EEG), especially during sleep.
• About 70% of children with LKS have seizures.
• 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.
• Some children with Landau Kleffner syndrome may also have intellectual disability.
• 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.

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.
• 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.
• 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.
• 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.

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.
• In some cases, immunotherapy may improve speech and seizures.
• 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.
• Speech therapy should be initiated as soon as possible to help children regain speech.
• Speech therapists may also recommend helping children learn sign language to help them find new ways to communicate.
• Special education may also be necessary in some cases.

NIH genetic and rare disease info

• NIH info on Landau-Kleffner syndrome

Landau-Kleffner syndrome is a rare disease.

Landau-Kleffner syndrome Resources
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