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Last updated:
05/01/2023
Years published: 1986, 1987, 1990, 1991, 1995, 1997, 2000, 2008, 2009, 2012, 2015, 2018
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.
In 2022, the International League Against Epilepsy (ILAE) recommended that Landau-Kleffner syndrome be considered a subtype of developmental/epileptic encephalopathy with spike wave activation on sleep (DEE-SWAS). These conditions are a spectrum of epilepsy syndromes in children characterized by a specific abnormal EEG pattern and variable degrees of cognitive regression. A child with a diagnosis of LKS may transition to another DEE-SWAS syndrome over time.
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of children with LKS also develops serious behavioral dysfunction, including hyperactivity, temper outbursts, or withdrawn behaviors but rarely the severe social impairments seen in autism spectrum disorders.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.
Treatment
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.
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
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
Landau Kleffner Syndrome Resources
TEXTBOOKS
Mantovani JF. Developmental regression, autism and epilepsy. In: Shapiro BK, Accardo PJ, eds. Autism Frontiers: Clinical Issues and Innovations. Baltimore, MD: Paul H. Brookes; 2008:49-56.
Mantovani JF. Landau-Kleffner Syndrome. In: The NORD Guide to Rare Disorders, Philadelphia, PA: Lippincott, Williams and Wilkins; 2003:547-8.
JOURNAL ARTICLES
Caraballo RH, Cejas N, Chamorro N, et al. Landau-Kleffner syndrome: A study of 29 patients. Seizure. 2014;23:98-104.
Conroy J, McGettigan PA, McCreary D, et al. Towards the identification of a genetic basis for Landau-Kleffner syndrome. Epilepsia 2014;55:858-65.
Devinsky O, Goldberg R, Miles D, et al. Episodic epileptic verbal auditory agnosia in Landau-Kleffner syndrome treated with combination diazepam and corticosteroids. J Child Neurol 2014;29:1291-8.
Lesca G, Rudolf G, Bruneau N, et al. GRIN2A mutations in acquired epileptic aphasia and related focal epilepsies and encephalopathies with specch and language dysfunction. Nat Genet 2013;45:1061.
Bast T, Richter S, Ebinger F, et al. Efficacy and tolerability of methylprednisolone pulse therapy in childhood epilepsies other than infantile spasms. Neuropediatrics 2014;45:378-85.
Stefanatos G: Changing perspectives on Landau-Kleffner Syndrome. The Clinical Neuropsychologist. 2011;25(6):936-988.
Robinson RO, Baird G, Robinson G, et al. Landau-Kleffner Syndrome: course and correlates with outcome. Dev Med Child Neurol. 2001;43:243-247.
Mantovani JF. Autistic regression and Landau-Kleffner syndrome: progress or confusion? Dev Med Child Neurol. 2000;42:349-353.
Lewine JD, Andrews R, Chez M, et al. Magnetencephalographic patterns of epileptiform activity in children with regressive autistic spectrum disorders. Pediatrics.1999;104:405-418.
Kaga M. Language disorders in Landau-Kleffner syndrome. J Child Neurol. 1999;14:118-22.
Lagae LG, et al. Successful use of intravenous immunoglobulins in Landau-Kleffner syndrome. Pediatr Neurol. 1998;18:165-8.
Landau WM and Kleffner FR. Syndrome of acquired aphasia with convulsive disorder in children. Neurology. 1998;51:1241-9.
Fayad MN, et al. Landau-Kleffner syndrome: consistent response to repeated intravenous gamma-globulin doses: a case report. Epilepsia.1997;38:489-94.
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.
INTERNET
Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Landau-Kleffner Syndrome; LKS. Entry No: 245570. Updated 9/8/15 Available at: https://omim.org/entry/245570 Accessed March 13, 2018.
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Learn more https://rarediseases.org/patient-assistance-programs/medicalert-assistance-program/Ensuring that patients and caregivers are armed with the tools they need to live their best lives while managing their rare condition is a vital part of NORD’s mission.
Learn more https://rarediseases.org/patient-assistance-programs/rare-disease-educational-support/This first-of-its-kind assistance program is designed for caregivers of a child or adult diagnosed with a rare disorder.
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