NORD gratefully acknowledges John F. Mantovani, MD, Medical Director, Mercy Kids Autism and Therapy Center, Mercy Children's Hospital-St. Louis, for assistance in the preparation of this report.
Landau Kleffner syndrome (LKS) is a rare childhood disorder characterized by the loss of language comprehension (auditory verbal agnosia) and verbal expression (aphasia) in association with severely abnormal electroencephalographic (EEG) findings during sleep and clinical seizures in most patients.
The symptoms typically begin between the ages of three and seven years although the condition 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of children with LKS also develops serious behavioral dysfunction, including hyperactivity, temper outbursts, or withdrawn behaviors but rarely the severe social impairments seen in autism spectrum disorders.
Approximately 70% of affected children have obvious seizures, most often focal with or without alteration of awareness and/or atypical absence in type.
The cause of Landau-Kleffner syndrome is unknown although a spectrum of epileptic conditions including LKS has been described in individuals with GRIN2A gene mutations and other candidate genes including RELN, BSN, EPHB2 and NID2 have been suggested. The response in some patients to immunosuppression has raised the question of autoimmune and other inflammatory mechanisms as potential contributors.
Landau-Kleffner syndrome is a rare disorder that affects twice as many males as females. Affected siblings and discordant monozygotic twins have been reported rarely.
In additional to language regression, the diagnosis requires the presence of severely epileptiform activity on EEG, particularly during non-REM sleep. Additional testing may include magnetoencephalography. Brain imaging with magnetic resonance imaging (MRI) is recommended to exclude structural lesions since several cases have resulted from brain tumors. 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. Some authors have suggested using a combination of corticosteroids and pulse 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. Augmentative and alternative communication devices and even 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 treatment with intravenous immunoglobulin. 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.
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Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Landau-Kleffner Syndrome; LKS. Entry No: 245570. Updated 9/8/15 Available at: http://omim.org/entry/245570 Accessed March 13, 2018.
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