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 typically begin between the ages of four and seven years. Affected children often appear to have acquired deafness since they fail to respond to verbal language and in some cases to nonverbal sounds. A significant minority of children develop serious behavioral dysfunction, including hyperactivity, temper outbursts, or withdrawn behaviors, but rarely the severe social impairments seen in autism.

Approximately 70% of affected children also have obvious seizures, most often simple or complex partial seizures and/or atypical absence in type.

The exact cause of Landau-Kleffner syndrome is not known. Many possible causes have been suggested including genetic factors, autoimmune disorders and other inflammatory processes.

Landau-Kleffner syndrome is a rare disorder that affects twice as many males as females. Affected siblings have been reported rarely.

Autism is a lifelong, nonprogressive neurologic disorder typically appearing before the age of thirty months. 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 low scores on standardized intelligence tests. The outlook for independent living may be improved with intensive training. (For more information on this disorder, choose "Autism" as your search term in the Rare Disease Database.)

Rett Syndrome is a rare neurodevelopmental disorder that appears to occur almost exclusively in females but can occur rarely in males. Infants and children with the disorder typically develop normally until about 7 to 18 months of age, when they may begin to lose previously acquired skills (developmental regression), such as purposeful hand movements and the ability to communicate. Additional abnormalities typically include slowing of head growth (acquired microcephaly); development of distinctive, uncontrolled (stereotypic) hand movements, such as hand clapping, rubbing, or "wringing"; and impaired control of voluntary movements required for coordination of walking (gait apraxia). Affected children also typically develop autistic-like behaviors, breathing irregularities, feeding and swallowing difficulties, growth retardation, and episodes of uncontrolled electrical activity in the brain (seizures).

Rett Syndrome results from a mutation (change) on the X chromosome that is transmitted as an X-linked trait. However, most cases are thought to represent new mutations that appear to occur spontaneously (sporadically) for unknown reasons. In some affected females, the disorder may result from mutations of a gene known as MECP2 that is located on the long arm (q) of chromosome X (Xq28). The MECP2 gene is thought to play an essential role in brain development. (For more information on this disorder, choose "Rett" as your search term in the Rare Disease Database.)

Asperger's syndrome is a neuropsychiatric disorder. Children with this disorder experience the inability to understand the feelings of others, abnormal single-mindedness, lack of verbal skills, insensitivity to social cues, withdrawal and obsessive indulgence in special interests. Many clinicians believe that Asperger's syndrome is a sub-type of autism that is differentiated by a later onset (i.e., it is usually not recognized before 30 months of age) and by the fact that speech generally is not delayed, as it often is in children with autism. The exact cause of Asperger's syndrome is unknown. (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
In additional to linguistic regression, the diagnosis requires the presence of severely epileptiform activity on EEG, particularly during sleep. Additional testing may include magnetoencephalography. Brain imaging with magnetic resonance imaging (MRI) is recommended to exclude structural lesions. Other testing includes behavioral and/or brainstem evoked audiometry and standardized psychometric and speech/language testing.

Treatment
The standard therapeutic approach begins with antiepileptic drugs, particularly "spike-suppressing" medications such as divalproex, ethosuximide, and benzodiazepines. Other antiepileptic drugs that may be beneficial are lamotrigine and felbamate.

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 children with little or no understanding of language. Special education classes for children with severe speech and language disorders may prove beneficial as well.

When antiepileptic drugs are ineffective, other approaches include the ketogenic diet or immunosuppression with oral corticosteroids. Treatment with intravenous immunoglobulin and calcium-channel blocking drugs may also be beneficial. A neurosurgical procedure called multiple subpial transection (MST) is being used for some children who fail to improve linguistically within two years and for those who develop steroid dependency or toxicity.

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

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