Information on the following diseases can be found in the Related Disorders section of this report:

• Autism
• Rett syndrome
• Asperger's syndrome
• Epilepsy

The symptoms of Landau-Kleffner syndrome may develop suddenly or slowly. In most cases, the first symptom is usually loss of the ability to understand speech (receptive aphasia), followed by loss of the ability to speak (expressive aphasia). The severity of aphasia varies from case to case. For example, some affected children eventually fail to recognize their own name and some lose their speech completely.

About two-thirds of affected children also experience convulsive epileptic seizures. Seizures often occur during the night. Most children with Landau-Kleffner syndrome have few seizures that are easily controlled with appropriate treatment. However, in rare cases, affected children may experience more numerous seizures that are harder to control.

Some children with Landau-Kleffner syndrome may have a general lack of awareness of environmental sounds and be unable to recognize previously familiar sounds (auditory agnosia), such as the telephone ringing or a dog barking. In some cases, aphasia and agnosia cause affected children to mistakenly appear deaf.

About 70 percent of children with Landau-Kleffner syndrome experience behavioral problems such as aggressiveness, eating difficulties, sleeping problems, depression, and/or hyperactivity. Some children may exhibit "autistic-like" behavior including avoidance of family members and friends, failure to make eye contact, insensitivity to pain, and/or aggression and rage attacks. In some cases, short and long-term memory, fine motor skills, and/or attention span may also be affected.

The severity of communication deficits associated with aphasia related to Landau-Kleffner syndrome often vary greatly and may depend upon the location and extent of dysfunction in the brain. Most children with Landau-Kleffner syndrome do not have seizures after the age of 15 years. Approximately 20 percent of children with this disorder eventually recover completely, even after repeated episodes of aphasia. However, many children experience ongoing speech and communication problems.

The exact cause of Landau-Kleffner syndrome is not known. One study suggested that this disorder may be inherited as an autosomal recessive genetic trait. However, that theory has yet to be proven. Other causes that have been suggested include a slow virus or an autoimmune or inflammatory process that affects the brain. Symptoms may develop due to defects (lesions) on one or both of the temporal lobes of the brain. The temporal lobes are responsible for numerous functions including processing language.

Landau-Kleffner syndrome is a rare disorder that affects twice as many males as females. The disorder was first identified in 1957 and approximately 200 cases have been reported in the medical literature. The disorder may often remain unrecognized and may therefore be underdiagnosed, making it difficult to determine the true frequency of Landau-Kleffner syndrome in the general population.

The symptoms typically begin between the ages of three and seven years and may slowly develop over several months or appear overnight. The younger an affected individual is when the symptoms initially appear, the more severe the symptoms tend to be. Most children with Landau-Kleffner syndrome are seizure free by the age of 15 years, and some children recover completely, without communication deficits. However, many children are left with severe auditory "agnosia" (the inability to recognize objects through the senses) and communication problems.

Symptoms of the following disorders can be similar to those of Landau- Kleffner syndrome. Comparisons may be useful for a differential diagnosis:

Autism is a nonprogressive neurological disorder that typically begins before the age of three years. It is characterized by language and communication deficits, withdrawal from social contacts, and extreme reactions to changes in the immediate environment. About 75 percent of children with autism have a low score on standardized intelligence tests (IQ). The earliest symptoms of autism may include a lack of response to other people and a marked preference for passive, solitary activities. Sensory responses (e.g., to sight and sound) may be unpredictable. Some affected children may appear indifferent to these stimuli, while others respond with intense emotional outbursts. Additional symptoms may include hyperactivity, temper tantrums, rhythmic rocking, sleep impairment, and/or eating problems. Speech and language development is generally delayed. (For more information on this disorder, choose "Autism" as your search term in the Rare Disease Database.)

Rett syndrome is a rare neurological disorder that begins during early childhood and is characterized by the progressive degeneration of the tissue of the brain (encephalopathy). The disorder affects females exclusively. Symptoms may include the loss of previously acquired intellectual and motor skills, developmental regression, and other neurological problems. The classical symptoms of Rett syndrome include repetitive sighing while breathing and repeated involuntary movements of the hands that appear as though the child is continuously washing their hands. Other symptoms may include withdrawal, inability to communicate, delusions, hallucinations, and/or dementia. (For more information on this disorder, choose "Rett" as your search term in the Rare Disease Database.)

Asperger's syndrome is a rare neuropsychiatric disorder characterized by the inability to understand other people's feelings, a lack of verbal skills, and behavioral abnormalities such as single-mindedness, social withdrawal, and over-sensitivity. Many scientists believe that Asperger's syndrome is a subtype of autism that is differentiated by a later onset (i.e., it is usually not recognized before 30 months of age) and the normal development of speech, which is delayed in children with autism. (For more information on this disorder, choose "Asperger" as your search term in the Rare Disease Database.)

The following disorder may be associated with Landau-Kleffner syndrome as a secondary characteristic. It is not necessary for a differential diagnosis:

Epilepsy is a group of disorders of the central nervous system characterized by repeated convulsive electrical disturbances in the brain. The major symptoms may include loss of consciousness, convulsions, spasms, sensory confusion, and disturbances of involuntary body functions (autonomic nervous system). Episodes of these symptoms are frequently preceded by an "aura," which is described as a feeling of uneasiness or discomfort. There are many different forms of epilepsy including generalized seizures (i.e., Grand Mal and Petit Mal) and partial seizures (i.e., Jacksonian seizures or Abdominal Seizures). (For more information on this disorder, choose "Epilepsy" as your search term in the Rare Disease Database.)

Diagnosis
The diagnosis of Landau-Kleffner syndrome may be confirmed by a detailed patient history and a thorough clinical evaluation that includes repeated testing of the electrical activity of the brain (electroencephalogram [EEG]). Readings from these tests are typically abnormal in children with this disorder. Abnormal EEG patterns seem to be most profound during prolonged periods of sleep. Additional diagnostic tests may include computed axial tomography (CAT Scan), magnetic resonance imaging (MRI), single photon emission computerized tomography/positron emission tomography (SPECT/PET Scans) and/or magnetoencehalography (MEG Scan).

Computerized tomography or magnetic resonance imaging of the brain may reveal abnormalities affecting certain areas of the brain that can result in epilepsy. During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of the brain's tissue structure. During MRI, a magnetic field and radio waves are used to create cross-sectional images of the brain. During a PET scan, three-dimensional images are produced that reflect the brain's chemical activity; such scanning helps physicians examine brain function and potentially locate the origin of seizure activity. A SPECT scan is used to detect changes in the cerebral blood flow that may indicate certain abnormalities that result in epilepsy.

Treatment
The treatment of Landau-Kleffner syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists who may need to systematically and comprehensively plan an affected child's treatment. Such specialists may include pediatricians, physicians who diagnose and treat neurological abnormalities (neurologists), speech pathologists, and/or other health care professionals.

Specific therapies for the treatment of Landau-Kleffner syndrome are symptomatic and supportive. Drugs that help to reduce seizure activity (antiepileptics) have had varying degrees of effectiveness (e.g., valproic acid and clobazam).

A supportive team approach for children with Landau-Kleffner syndrome may help to reestablish some communication skills. Appropriate speech and language therapy is important for affected children. Sign language training may be useful for some affected chilren with little or no understanding of language. Special education classes for children with severe speech and language disorders may prove beneficial as well.

A new surgical procedure is being investigated for the treatment of children with Landau-Kleffner syndrome. During this procedure, known as a subpial transection, certain nerve pathways in the brain are severed. When successful, it is hoped that this surgery may restore hearing and speech as well as eliminate seizures. More studies are needed to determine the long-term safety and effectiveness of this surgery for the treatment of Landau- Kleffner syndrome. For additional information on this procedure, contact:

Rush Presbyterian
St. Lukes Medical Center
1753 W. Congress Parkway
Chicago, IL 60612
(312) 942-5000
or
(312) 942-5939

Corticosteroid drugs are being tested for the treatment of children with Landau-Kleffner syndrome. In many cases, these drugs (i.e., prednisone), if administered early in the course of the disease, may restore speech and eliminate seizures. More studies are needed to determine the long-term safety and effectiveness of these drugs for the treatment of Landau-Kleffner syndrome.

According to the medical literature, administration of intravenous immunoglobulin (IVIG) has led to an improvement of symptoms of individuals with Landau-Kleffner syndrome. However, most of these reports are single case accounts. More research is needed to determine the long-term safety and effectiveness for this potential treatment for Landau-Kleffner syndrome.

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