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Landau-Kleffner syndrome(FESD)

MedGen UID:
79465
Concept ID:
C0282512
Disease or Syndrome
Synonyms: Acquired aphasia with convulsive disorder; Acquired epileptiform aphasia; APHASIA, ACQUIRED, WITH EPILEPSY; Epilepsy with neurodevelopmental defects; EPILEPSY, FOCAL, WITH SPEECH DISORDER AND WITH OR WITHOUT IMPAIRED INTELLECTUAL DEVELOPMENT; FESD
SNOMED CT: Acquired aphasia with epilepsy (230438007); Acquired epileptic aphasia (230438007); Landau-Kleffner syndrome (230438007); Aphasia co-occurrent with epilepsy (230438007)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): GRIN2A (16p13.2)
 
Monarch Initiative: MONDO:0009509
OMIM®: 245570
Orphanet: ORPHA98818

Disease characteristics

Excerpted from the GeneReview: GRIN2A-Related Speech Disorders and Epilepsy
GRIN2A-related speech disorders and epilepsy are characterized by speech disorders in all affected individuals and a range of epilepsy syndromes present in about 90%. Severe speech disorders observed can include dysarthria and speech dyspraxia, and both receptive and expressive language delay/regression; more mildly affected individuals may display subtly impaired intelligibility of conversational speech. Epilepsy features include seizure onset usually between ages three and six years, focal epilepsy with language and/or global developmental regression, and electroencephalogram (EEG) showing continuous spike-and-wave discharges in sleep or very active centrotemporal discharges. Seizure types include seizures associated with aura of perioral paresthesia, focal or focal motor seizures (often evolving to generalized tonic-clonic), and atypical absence seizures. Epilepsy syndromes can include: Landau-Kleffner syndrome (LKS), epileptic encephalopathy with continuous spike-and-wave during sleep (ECSWS), childhood epilepsy with centrotemporal spikes (CECTS), atypical childhood epilepsy with centrotemporal spikes (ACECTS), autosomal dominant rolandic epilepsy with speech dyspraxia (ADRESD), and infantile-onset epileptic encephalopathy. [from GeneReviews]
Authors:
Kenneth A Myers  |  Ingrid E Scheffer   view full author information

Additional description

From OMIM
Focal epilepsy with speech disorder is a childhood-onset seizure disorder with a highly variable phenotype. Seizures typically occur in the temporal lobe, or rolandic brain region, which affects speech and language, and electroencephalogram (EEG) characteristically shows centrotemporal spike-wave discharges. EEG abnormalities often occur during sleep and may manifest as continuous spike-wave discharges during slow-wave sleep (CSWS or CSWSS). FESD represents an electroclinical spectrum that ranges from severe early-onset seizures associated with delayed psychomotor development, persistent speech difficulties, and impaired intellectual development to a more benign entity characterized by childhood onset of mild or asymptomatic seizures associated with transient speech difficulties followed by remission of seizures in adolescence and normal psychomotor development. There is incomplete penetrance and intrafamilial variability, even among family members who carry the same GRIN2A mutation (summary by Lesca et al., 2013; Lemke et al., 2013; Carvill et al., 2013). The disorder represented here encompasses several clinical entities, including Landau-Kleffner syndrome (LKS), epileptic encephalopathy with continuous spike and wave during slow-wave sleep (ECSWS; CSWSS), autosomal dominant rolandic epilepsy, impaired intellectual development, and speech dyspraxia (ADRESD; RESDAD), and benign epilepsy with centrotemporal spikes (BECTS; see 117100). LKS is classically described as a childhood-onset variant of epileptic aphasia. It is associated with EEG abnormalities occurring in the temporal lobe of the language-dominant hemisphere, even in the absence of overt clinical seizures. LKS is sometimes referred to as an 'acquired aphasia' because most affected children show normal psychomotor development until the onset of seizures, usually between 3 and 7 years, although some may have prior delayed development. A hallmark of the disorder is severe impairment in auditory language comprehension and speech. Some patients may also have persistent intellectual disability or behavioral abnormalities reminiscent of autism or attention deficit-hyperactivity disorder. EEG abnormalities typically include centrotemporal spikes suggestive of rolandic epilepsy or continuous spike and waves during slow-wave sleep. The presence of CSWS is associated with more widespread behavioral and cognitive regression than LKS, although the 2 disorders may be considered part of a spectrum. There is controversy about the precise definition of LKS and its relationship to CSWS that stems mainly from the phenotypic heterogeneity of the disorder (summary by Stefanatos, 2011).  http://www.omim.org/entry/245570

Clinical features

From HPO
Pes cavus
MedGen UID:
675590
Concept ID:
C0728829
Congenital Abnormality
An increase in height of the medial longitudinal arch of the foot that does not flatten on weight bearing (i.e., a distinctly hollow form of the sole of the foot when it is bearing weight).
Small for gestational age
MedGen UID:
65920
Concept ID:
C0235991
Finding
Smaller than normal size according to sex and gestational age related norms, defined as a weight below the 10th percentile for the gestational age.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Aphasia
MedGen UID:
8159
Concept ID:
C0003537
Mental or Behavioral Dysfunction
An acquired language impairment of some or all of the abilities to produce or comprehend speech and to read or write.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Speech apraxia
MedGen UID:
78112
Concept ID:
C0264611
Disease or Syndrome
A type of apraxia that is characterized by difficulty or inability to execute speech movements because of problems with coordination and motor problems, leading to incorrect articulation. An increase of errors with increasing word and phrase length may occur.
Focal impaired awareness seizure
MedGen UID:
543022
Concept ID:
C0270834
Disease or Syndrome
Focal impaired awareness seizure (or focal seizure with impaired or lost awareness) is a type of focal-onset seizure characterized by some degree (which may be partial) of impairment of the person's awareness of themselves or their surroundings at any point during the seizure.
Atonic seizure
MedGen UID:
78735
Concept ID:
C0270846
Disease or Syndrome
Atonic seizure is a type of motor seizure characterized by a sudden loss or diminution of muscle tone without apparent preceding myoclonic or tonic event lasting about 1 to 2 seconds, involving head, trunk, jaw, or limb musculature.
Delayed speech and language development
MedGen UID:
105318
Concept ID:
C0454644
Finding
A degree of language development that is significantly below the norm for a child of a specified age.
Bilateral tonic-clonic seizure
MedGen UID:
141670
Concept ID:
C0494475
Sign or Symptom
A bilateral tonic-clonic seizure is a seizure defined by a tonic (bilateral increased tone, lasting seconds to minutes) and then a clonic (bilateral sustained rhythmic jerking) phase.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Focal-onset seizure
MedGen UID:
199670
Concept ID:
C0751495
Disease or Syndrome
A focal-onset seizure is a type of seizure originating within networks limited to one hemisphere. They may be discretely localized or more widely distributed, and may originate in subcortical structures.
Autistic behavior
MedGen UID:
163547
Concept ID:
C0856975
Mental or Behavioral Dysfunction
Persistent deficits in social interaction and communication and interaction as well as a markedly restricted repertoire of activity and interest as well as repetitive patterns of behavior.
Bilateral tonic-clonic seizure with focal onset
MedGen UID:
164077
Concept ID:
C0877017
Disease or Syndrome
A bilateral tonic-clonic seizure with focal onset is a focal-onset seizure which progresses into a bilateral tonic-clonic phase.
Attention deficit hyperactivity disorder
MedGen UID:
220387
Concept ID:
C1263846
Mental or Behavioral Dysfunction
Attention-deficit/hyperactivity disorder (ADHD) is a behavioral disorder that typically begins in childhood and is characterized by a short attention span (inattention), an inability to be calm and stay still (hyperactivity), and poor impulse control (impulsivity). Some people with ADHD have problems with only inattention or with hyperactivity and impulsivity, but most have problems related to all three features.\n\nIn people with ADHD, the characteristic behaviors are frequent and severe enough to interfere with the activities of daily living such as school, work, and relationships with others. Because of an inability to stay focused on tasks, people with inattention may be easily distracted, forgetful, avoid tasks that require sustained attention, have difficulty organizing tasks, or frequently lose items.\n\nHyperactivity is usually shown by frequent movement. Individuals with this feature often fidget or tap their foot when seated, leave their seat when it is inappropriate to do so (such as in the classroom), or talk a lot and interrupt others.\n\nImpulsivity can result in hasty actions without thought for the consequences. Individuals with poor impulse control may have difficulty waiting for their turn, deferring to others, or considering their actions before acting.\n\nMore than two-thirds of all individuals with ADHD have additional conditions, including insomnia, mood or anxiety disorders, learning disorders, or substance use disorders. Affected individuals may also have autism spectrum disorder, which is characterized by impaired communication and social interaction, or Tourette syndrome, which is a disorder characterized by repetitive and involuntary movements or noises called tics.\n\nIn most affected individuals, ADHD continues throughout life, but in about one-third of individuals, signs and symptoms of ADHD go away by adulthood.
Developmental regression
MedGen UID:
324613
Concept ID:
C1836830
Disease or Syndrome
Loss of developmental skills, as manifested by loss of developmental milestones.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Continuous spike and waves during slow sleep
MedGen UID:
812733
Concept ID:
C3806403
Finding
Diffuse, bilateral and recently also unilateral or focal localization spike-wave occurring in slow sleep or non-rapid eye movement sleep.
EEG with centrotemporal focal spike waves
MedGen UID:
868454
Concept ID:
C4022848
Finding
EEG with focal sharp transient waves in the centrotemporal region of the brain (also known as the central sulcus), i.e., focal sharp waves of a duration less than 80 msec followed by a slow wave.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Primary microcephaly
MedGen UID:
383046
Concept ID:
C2677180
Finding
Head circumference below 2 standard deviations below the mean for age and gender at birth.
Short nose
MedGen UID:
343052
Concept ID:
C1854114
Finding
Distance from nasion to subnasale more than two standard deviations below the mean, or alternatively, an apparently decreased length from the nasal root to the nasal tip.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Landau-Kleffner syndrome in Orphanet.

Professional guidelines

PubMed

de Lima TA, Zuanetti PA, Nunes MEN, Hamad APA
World J Pediatr 2023 Aug;19(8):715-726. Epub 2022 Oct 25 doi: 10.1007/s12519-022-00629-y. PMID: 36282408
McTague A, Cross JH
CNS Drugs 2013 Mar;27(3):175-84. doi: 10.1007/s40263-013-0041-6. PMID: 23397290
Mikati MA, Shamseddine AN
Paediatr Drugs 2005;7(6):377-89. doi: 10.2165/00148581-200507060-00006. PMID: 16356025

Recent clinical studies

Etiology

Furley K, Mehra C, Goin-Kochel RP, Fahey MC, Hunter MF, Williams K, Absoud M
Cortex 2023 Dec;169:5-17. Epub 2023 Sep 27 doi: 10.1016/j.cortex.2023.09.001. PMID: 37839389
Besag FMC, Vasey MJ
Epilepsy Behav 2019 Nov;100(Pt B):106210. Epub 2019 Jun 10 doi: 10.1016/j.yebeh.2019.03.015. PMID: 31196824
Camfield P, Camfield C
Neurosci Biobehav Rev 2019 Jan;96:210-218. Epub 2018 Dec 8 doi: 10.1016/j.neubiorev.2018.12.008. PMID: 30537476
McTague A, Cross JH
CNS Drugs 2013 Mar;27(3):175-84. doi: 10.1007/s40263-013-0041-6. PMID: 23397290
Tuchman R, Rapin I
Lancet Neurol 2002 Oct;1(6):352-8. doi: 10.1016/s1474-4422(02)00160-6. PMID: 12849396

Diagnosis

Tuft M, Årva M, Bjørnvold M, Wilson JA, Nakken KO
Tidsskr Nor Laegeforen 2015 Dec 1;135(22):2061-4. doi: 10.4045/tidsskr.15.0162. PMID: 26627294
Stafstrom CE, Carmant L
Cold Spring Harb Perspect Med 2015 Jun 1;5(6) doi: 10.1101/cshperspect.a022426. PMID: 26033084Free PMC Article
Kumar A, Chugani HT
Handb Clin Neurol 2013;111:767-76. doi: 10.1016/B978-0-444-52891-9.00079-8. PMID: 23622224
Stefanatos G
Clin Neuropsychol 2011 Aug;25(6):963-88. doi: 10.1080/13854046.2011.614779. PMID: 21955111
Steinlein OK
Expert Rev Neurother 2009 Jun;9(6):825-33. doi: 10.1586/ern.09.49. PMID: 19496686

Therapy

Tuft M, Årva M, Bjørnvold M, Wilson JA, Nakken KO
Tidsskr Nor Laegeforen 2015 Dec 1;135(22):2061-4. doi: 10.4045/tidsskr.15.0162. PMID: 26627294
Mikati MA, Shamseddine AN
Paediatr Drugs 2005;7(6):377-89. doi: 10.2165/00148581-200507060-00006. PMID: 16356025
Tuchman R, Rapin I
Lancet Neurol 2002 Oct;1(6):352-8. doi: 10.1016/s1474-4422(02)00160-6. PMID: 12849396
Dulac O
Epilepsia 2001;42 Suppl 3:23-6. doi: 10.1046/j.1528-1157.2001.042suppl.3023.x. PMID: 11520318
Arnold ST, Dodson WE
Baillieres Clin Neurol 1996 Dec;5(4):783-802. PMID: 9068881

Prognosis

Specchio N, Wirrell EC, Scheffer IE, Nabbout R, Riney K, Samia P, Guerreiro M, Gwer S, Zuberi SM, Wilmshurst JM, Yozawitz E, Pressler R, Hirsch E, Wiebe S, Cross HJ, Perucca E, Moshé SL, Tinuper P, Auvin S
Epilepsia 2022 Jun;63(6):1398-1442. Epub 2022 May 3 doi: 10.1111/epi.17241. PMID: 35503717
Tuft M, Årva M, Bjørnvold M, Wilson JA, Nakken KO
Tidsskr Nor Laegeforen 2015 Dec 1;135(22):2061-4. doi: 10.4045/tidsskr.15.0162. PMID: 26627294
Stafstrom CE, Carmant L
Cold Spring Harb Perspect Med 2015 Jun 1;5(6) doi: 10.1101/cshperspect.a022426. PMID: 26033084Free PMC Article
Steinlein OK
Expert Rev Neurother 2009 Jun;9(6):825-33. doi: 10.1586/ern.09.49. PMID: 19496686
Mikati MA, Shamseddine AN
Paediatr Drugs 2005;7(6):377-89. doi: 10.2165/00148581-200507060-00006. PMID: 16356025

Clinical prediction guides

Sivathamboo S, Myers KA, Pattichis A, White EJ, Ku KN, O'Brien TJ, Perucca P, Kwan P
Epilepsia Open 2023 Sep;8(3):1157-1168. Epub 2023 Jun 12 doi: 10.1002/epi4.12772. PMID: 37277988Free PMC Article
Jacob J
Epilepsia 2016 Feb;57(2):182-93. Epub 2015 Dec 19 doi: 10.1111/epi.13272. PMID: 26682992
Schmitt B
Neuropediatrics 2015 Jun;46(3):171-80. Epub 2015 May 12 doi: 10.1055/s-0035-1551574. PMID: 25965811
Issa NP
Pediatr Neurol 2014 Sep;51(3):287-96. Epub 2014 May 4 doi: 10.1016/j.pediatrneurol.2014.04.029. PMID: 25160535
Metz-Lutz MN, Filippini M
Epilepsia 2006;47 Suppl 2:71-5. doi: 10.1111/j.1528-1167.2006.00695.x. PMID: 17105467

Recent systematic reviews

Chapman KE, Haubenberger D, Jen E, Tishchenko A, Nguyen T, McMicken C
Epilepsy Res 2024 Jan;199:107278. Epub 2023 Dec 8 doi: 10.1016/j.eplepsyres.2023.107278. PMID: 38157757
Hajtovic S, LoPresti MA, Zhang L, Katlowitz KA, Kizek DJ, Lam S
J Neurosurg Pediatr 2022 Jun 1;29(6):667-680. Epub 2022 Mar 18 doi: 10.3171/2022.1.PEDS222. PMID: 35303699
Moresco L, Bruschettini M, Calevo MG, Siri L
Cochrane Database Syst Rev 2020 Nov 6;11(11):CD013132. doi: 10.1002/14651858.CD013132.pub2. PMID: 33174224Free PMC Article
Sigafoos J, O'Reilly MF, Ledbetter-Cho K, Lim N, Lancioni GE, Marschik PB
Neurosci Biobehav Rev 2019 Jan;96:56-71. Epub 2018 Nov 24 doi: 10.1016/j.neubiorev.2018.11.014. PMID: 30481529
van den Munckhof B, van Dee V, Sagi L, Caraballo RH, Veggiotti P, Liukkonen E, Loddenkemper T, Sánchez Fernández I, Buzatu M, Bulteau C, Braun KP, Jansen FE
Epilepsia 2015 Nov;56(11):1738-46. Epub 2015 Sep 4 doi: 10.1111/epi.13128. PMID: 26337159

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