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NORD is very grateful to John F. Mantovani, MD, Chairman of Pediatrics & Section Chief of Child Neurology, Medical Director of Children's Therapy & Development Center, Mercy Children's Hospital, for assistance in the preparation of this report.
Landau Kleffner syndrome (LKS) is a childhood disorder characterized by the loss of comprehension and expression of verbal language (aphasia) in association with severely abnormal electroencephalic (EEG) findings that often result in seizures.
The symptoms typically begin between the ages of three and seven years although it may rarely occur in children as young as 18 months of age. 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significant minority of children develop serious behavioral dysfunction, including hyperactivity, temper outbursts, or withdrawn behaviors, but rarely the severe social impairments seen in autism.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 neurodevelopmental condition typically appearing before the age of thirty months. It is characterized by impairments in social interaction, communication and restricted or stereotyped patterns of behavior. Between 30 and 50% of affected children have a history of developmental regression affecting language, social and behavioral functioning, which usually occurs between 18 and 30 months of age. About 50 percent of children with autism have low scores on standardized intelligence tests. The clinical expression and severity of autism varies widely. The functional outlook for those with autism is often improved with intensive behavioral and developmental interventions. (For more information on this disorder, choose "Autism" as your search term in the Rare Disease Database.)
Rett syndrome is a rare neurodevelopmental disorder due to a known gene mutation. It occurs almost exclusively in females but can occur very rarely in males. Infants and children with the disorder typically develop normally until between 7 and 18 months of age, when they begin to lose previously acquired skills (developmental regression), including purposeful hand movements and verbal communication.. Associated 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 breathing irregularities, feeding and swallowing difficulties, growth retardation, and seizures..
Rett syndrome results from a mutation (change) in the MECP2 gene on the X chromosome.. Most cases are thought to represent new mutations that occur spontaneously (sporadically) for unknown reasons. The MECP2 gene is known to play an essential role in the development of normal brain connections (synapses) and circuit formation. (For more information on this disorder, choose "Rett" 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 seizures which are manifest by clinical changes in consciousness, muscle activity or other neurological functions caused by electrochemical disturbances in the brain. The major symptoms include loss of consciousness, convulsions, body-jerking, sensory loss, confusion, and disturbances of involuntary body functions (autonomic nervous system). EEGs often show characteristic patterns of electrical discharge even in-between the clinical episodes. . There are many different forms of epilepsy including primary generalized which can manifest by convulsive motor movements or staring unresponsiveness and partial seizures which may be preceded by an "aura", which is described as a feeling of vague discomfort or change in sensation and lead to varied combinations of motor and sensory alterations. (For more information on this disorder, choose "Epilepsy" as your search term in the Rare Disease Database.)
In additional to language 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 including behavioral and/or brainstem evoked audiometry and standardized psychometric and speech/language testing are helpful to exclude hearing loss and provide the basis for therapies to aide in recovery.
The standard therapeutic approach begins with antiepileptic drugs, particularly "spike-suppressing" medications such as divalproex, ethosuximide, levitiracetam, 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) has been used in some centers for 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:
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Mantovani JF. Landau-Kleffner Syndrome. In: The NORD Guide to Rare Disorders, Philadelphia, PA: Lippincott, Williams and Wilkins; 2003:547-8.
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Fayad MN, et al. Landau-Kleffner syndrome: consistent response to repeated intravenous gamma-globulin doses: a case report. Epilepsia. 1997;38:489-94.
Tharpe AM, et al., Landau-Kleffner syndrome: acquired epileptic aphasia in children. J Am Acad Audiol. 1994;5:146-50.
Lerman P, et al. Effect of early corticosteroid therapy for Landau-Kleffner syndrome. Dev Med Child Neurol. 1991;33:257-60
Bishop DV, et al. Age of onset and outcome in 'acquired aphasia with convulsive disorder' (Landau-Kleffner syndrome). Dev Med Child Neurol. 1985;27:705-12.
Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Landau-Kleffner Syndrome; LKS. Entry No: 245570. Last Edited August 31, 2005. Available at: http://www.ncbi.nlm.nih.gov/omim/. Accessed March 12, 2012.
Report last updated: 2012/03/15 00:00:00 GMT+0