Diagnostic Challenges and Consideration of Landau–Kleffner Syndrome as a Differential Diagnosis for Language Disorders: A Case Report

ABSTRACT

Landau–Kleffner syndrome is an important differential diagnosis in children with language disorders and psychiatric symptoms. Clinicians face challenges in multilingual settings, where failure to acquire a second language and language‐specific assessment limitations can hinder timely recognition. Timely diagnosis and multidisciplinary treatment are important for favorable long‐term outcomes.

1. Introduction

1.1. Overview of Symptoms

Landau–Kleffner syndrome (LKS) is a rare, age‐dependent epileptic encephalopathy characterized by profound loss of previously acquired language skills and sleep‐activated epileptiform activity on electroencephalogram (EEG) in children. Onset typically occurs between 3 and 10 years of age [1, 2, 3].

Research on LKS shows that multiple language domains are affected. Receptive language, particularly auditory comprehension, is typically the most profoundly impaired domain, often manifesting as auditory verbal agnosia. Expressive language is also frequently disrupted, with symptoms ranging from reduced vocabulary and sentence complexity to complete loss of speech [1, 4, 5, 6, 7, 8]. In addition, deficits in phonological processing and syntax are common. Some children exhibit apraxia‐like speech features, although these are usually secondary to language dysfunction [4, 5].

EEG anomalies consist of predominantly bilateral multifocal spikes during wakefulness and a pattern of (near‐)continuous spike‐and‐wave activity during sleep (CSWS) [2]. Seizures, including partial motor, (atypical) absence, or generalized tonic–clonic episodes occur in approximately two thirds of patients [6]. The condition is frequently associated with (social) cognitive deficits and psychiatric abnormalities including hyperactivity, impulsivity, attention deficits, working memory impairments, anxiety, depression and autism‐like behaviors [2, 6, 7, 8]. Typically, no hearing impairments are present, and no other neurological disorders are observed apart from epilepsy. Nonverbal intelligence is usually within the average range. The combination of language disorder and psychiatric abnormalities can significantly impact the child's daily functioning and overall quality of life.

1.2. Etiology and Genetic Aspects

The etiology of LKS remains incompletely understood. In certain cases, mutations in the GRIN2A gene (16p13.2) encoding a subunit of the N‐methyl‐D‐aspartate (NMDA)‐type glutamate receptor have been identified. Turner et al. described individuals with GRIN2A mutations presenting with speech apraxia without epilepsy, emphasizing that language dysfunction may arise independently of seizure activity. These findings support the concept of LKS within a broader GRIN2A‐related neurodevelopmental continuum, alongside possible autoimmune and other developmental contributors [4, 9, 10, 11, 12].

1.3. Treatment Approaches

Several antiepileptic drugs, including benzodiazepines, valproic acid, sultiame and ethosuximide have demonstrated efficacy in controlling seizures [13]. Corticosteroids have shown a particularly beneficial effect in improving language functions [14]. Children with CSWS (spike wave index (SWI) > 85%) and near‐CSWS (defined as SWI 40%–85%) had no clinically relevant differences in symptom presentation and impairment, so clinical presentation and symptom severity should determine the appropriate therapeutic approach [14]. A recent randomized controlled trial examined cognitive outcomes in children with epileptic encephalopathies with spike‐and‐wave activation in sleep (EE‐SWAS) treated with either corticosteroids or clobazam. After 6 months of treatment, a significantly higher number of children in the corticosteroid group showed an improvement of at least 11.25 IQ points, while no such improvement was seen in the clobazam group [15].

1.4. Prognosis

Early initiation of intensive speech therapy at the time of diagnosis is also essential to optimize outcomes [6]. The prognosis of LKS varies considerably [6, 16]. Seizures, when present, as well as CSWS can often be controlled with antiepileptic drugs and usually remit spontaneously around puberty [6]. In many patients, long‐term language impairments with high interindividual variability will remain [16, 17]. According to one study, residual impairments were more severe in patients with a longer duration of EEG abnormalities and an earlier age at onset [17].

1.5. Diagnostic Challenges in LKS

LKS is a specific subtype within the spectrum of EE‐SWAS. It is distinct due to its primary impact on language, setting it apart from other EE‐SWAS with usual dominant seizures and multiple affected developmental domains. In self‐limited epilepsy with centrotemporal spikes (SeLECTS), children might experience mild language or learning difficulties, but profound loss of language skills is unusual. However, SeLECTs may progress to EE‐SWAS, either temporarily or for a prolonged period [2].

The presence of shared clinical features makes distinguishing LKS from other (more prevalent) psychiatric disorders difficult and often delays diagnosis and early initiation of treatment. Autism‐spectrum disorder (ASD), Attention‐Deficit/Hyperactivity Disorder (ADHD), anxiety disorder or depression are important differential diagnoses due to the substantial overlap in symptoms [7, 8, 13, 18].

Diagnosing language (development) disorders such as LKS poses particular challenges in non‐native speakers. Multilingual upbringing may change the pattern of language acquisition compared to monolingual peers. Assessing language proficiency in each language, especially the native language, is essential for obtaining valid results. However, standardized tests often fail to account for multilingualism, which can significantly hinder accurate evaluations in clinical settings [19].

Some patients with LKS may present with apraxia‐like speech problems, usually secondary to language dysfunction. When speech difficulties primarily reflect impaired motor planning and coordination, childhood apraxia of speech (CAS) should be considered. Unlike LKS, CAS is characterized by early hypotonia, feeding issues, limited babbling, delayed first words, and persistent unintelligible speech [5].

1.6. Case Presentation

Here, we present the case of a 9‐year‐old boy who experienced initial difficulties in acquiring the German language after immigration, alongside behavioral and (social) cognitive deficits. Ultimately, he was diagnosed with Landau–Kleffner syndrome. This case illustrates the diagnostic challenges posed by his non‐native linguistic background and the presence of additional psychiatric symptoms, which complicated the differential diagnosis for his language disorder.

2. Case Description

2.1. Case History

A 9‐year‐old boy was referred to our child psychiatric day clinic by his teacher who was concerned about limited social interactions with peers and delays in language acquisition. He was almost exclusively playing alone, showed anxious behaviors towards classmates and teachers and had difficulties making and keeping eye contact. The family had immigrated from Albania to Germany approximately 3.5 years prior. For 3 years, the child attended a language support class for non‐native speakers, receiving four to 6 h of structured German training per day. All lessons and social interactions at school were conducted in German. At home, he was exposed exclusively to Albanian. Despite this consistent language training, he was unable to speak and understand German. He also had difficulties expressing himself and following commands in his native language Albanian. This regression in both languages could not be explained by second‐language dominance or attrition. The teacher interpreted the behavior as indicative of autism, which is why he was referred to our institute.

The parents and teachers reported that he also displayed a poor sense of direction and an impaired spatial memory. Although the route to school and the school grounds did not change over the years, the patient struggled to find his classroom. He also had memory problems such as not remembering what he had done the previous day.

2.2. Medical, Family and Psycho‐Social History

The pregnancy was unremarkable and the patient was born full‐term with no complications. Language, psychosocial and motor development were unremarkable up to the age of approximately 5.5 years. At the age of 2, he began learning English by watching internet videos, and within a short time, he was able to communicate at an intermediate level in the foreign language. The patient had lived in Albania until the age of 5 and had then moved to Germany with his family. At this time, he began to show slight language regression in his mother tongue Albanian. The parents reported that he struggled to understand spoken language and frequently needed information to be repeated. The parents interpreted the language regression as a difficulty in adapting to the new language.

No other pre‐existing conditions or diseases were known. His sister reported that she had been suffering from seizures during her childhood, but she had never received medical treatment for this condition. She stated that the seizures had remitted during adolescence. The parents reported that the patient's aunt had also suffered from epilepsy during childhood. Further details could not be determined.

3. Diagnostic Assessments

In our psychiatric assessment, the patient showed symptoms of an expressive and receptive language disorder. The patient was mostly speaking Albanian or English with very limited vocabulary in both. As no standardized language tests were available in the patient's native language, a state‐certified interpreter assisted in evaluating his Albanian skills. He was unable to speak or understand German. He was able to maintain eye contact with the investigator. Non‐verbal communication was age‐appropriate and unremarkable. Although he expressed empathy and interest in social interaction with peers, he initially continued to play mostly alone, displayed anxious behavior towards other patients and avoided social interaction in our day clinic. He explained this behavior by saying that he was afraid of the interaction because of the language barrier.

The physical examination including a thorough neurological examination was unremarkable. A magnetic resonance imaging (MRI) scan of the brain revealed normal age‐appropriate findings with no evidence of structural abnormalities.

The Autism Diagnostic Observation Schedule (ADOS) was unremarkable.

Considering the symptoms and their impact on the patient, the Clinical Global Impression—severity scale (CGI‐S) was scored a 6, indicating a classification of “severely ill.” This reflects significant impairments in daily functioning, development, and social interaction, which were primarily due to the symptoms of LKS.

The initial EEG recording showed an age‐appropriate irregular high‐voltage background activity within the alpha band. Additionally, a continuous spike focus was observed, occasionally manifesting as a spike–wave configuration, along with short episodes of spike–wave series bilaterally in the centrotemporal region.

A long‐term video‐EEG recording over 115 h, conducted in a neuropediatric clinic, demonstrated focal epileptiform discharges originating from the left frontotemporal lobe. During wakefulness, the SWI (percentage of seconds with epileptiform potentials) was at around 30%; during (Non‐REM) sleep, SWI increased > 70%, compatible with near‐CSWS.

Single whole exome sequencing did not identify possible alterations (copy number variations, single nucleotide variants) associated with epilepsy.

4. Diagnosis and Treatment

Based on the first EEG, compatible with Rolandic Epilepsy (SeLECTS), antiseizure medication with sultiame was initiated. Following video‐EEG monitoring that revealed near‐CSWS, and in the presence of language disorder and behavioral disturbances, a diagnosis of LKS was established. Treatment with high‐dose methylprednisolone pulses was initiated with intravenous infusions at a dosage of 20 mg/kg body weight for 3 days, followed by oral administration weekly during the first month, bi‐weekly during the second month, and monthly from the third month onwards. Due to adverse effects (nausea), the dosage of methylprednisolone was reduced to 8.5 mg/kg body weight orally after the second week of treatment. The patient participated in cognitive‐behavioral therapy (CBT) sessions after improving his German skills, with the aim of identifying and restructuring maladaptive thoughts and behaviors associated with anxiety. After 6 months of multimodal therapy in our day clinic, speech therapy, anticonvulsant, steroid therapy and CBT were continued in an outpatient setting. Methylprednisolone therapy was discontinued after 9 months following the continued improvement in both language function and EEG parameters.

5. Outcome, Follow Up and Prognosis

Two weeks after the initiation of sultiame, the patient started to pick up more German vocabulary. When the patient was discharged from our clinic 2 months after beginning the high‐dose methylprednisolone therapy in combination with the anticonvulsant therapy and 6 months after CBT, interaction with others significantly improved and observable anxious behaviors decreased. He demonstrated improved expressive and receptive language skills both in German and English as well as in his mother tongue (as confirmed by his parents and translators). He was able to speak fluently and to maintain a daily conversation. Working memory also improved based on clinical impression. At the time of discharge from the clinic, his symptoms and impairments were reevaluated using the Clinical Global Impression—Improvement Scale (CGI‐I), where he achieved a score of 2, indicating a classification of ‘much improved’.

A follow‐up EEG during wakefulness (2 months after the implementation of the multimodal treatment) showed an age‐appropriate pattern with a predominant alpha rhythm, interspersed with slower frequency activity, without lateralization, focal findings or epileptiform discharges. After his treatment at our day clinic, he started attending a special school focused on speech therapy.

The 3‐month follow‐up video‐EEG recording also showed focal epileptiform discharges originating from the left frontotemporal lobe. During wakefulness, the SWI was around 15%–20%; during (Non‐REM) sleep, SWI was approximately 40%. There were transient increases up to 70%, but overall the findings were less pronounced than in the initial EEG. A similar EEG pattern was observed 9 months after the initiation of therapy.

At the six‐month follow‐up visit, the patient was able to communicate proficiently in German. Although his vocabulary had not yet reached age‐appropriate levels, it was sufficient to enable conversation without significant difficulty. According to the teachers' evaluation, his progress in expanding his vocabulary was age‐appropriate. He did not show any problems with orientation, memory or anxiety.

Despite not having been treated for 2 years since the onset of symptoms, suggesting prolonged exposure to epileptic activity, the patient made considerable progress in language development and exhibited only minimal anxiety. Nevertheless, considering the current state of evidence, prognostic assessment remains difficult.

6. Discussion

6.1. Recognition of LKS in Psychiatric Settings

LKS is a distinct subtype of EE‐SWAS and it is believed that epileptic activity is partially responsible for variable cognitive, language, behavioral, and motor abnormalities [2]. Due to the common presentation with cognitive and psychiatric abnormalities [2, 6, 7, 8], patients with epileptic encephalopathies may initially present to child psychiatry services. The rarity of the condition, complex presentation, especially in psychiatric settings with a likely focus on the behavioral deficits by the assessing professionals, symptom overlap with (more prevalent) psychiatric disorders and intermittent epileptic activity (often only during sleep) may delay diagnosis.

6.2. Differentiating LKS From Autism Spectrum Disorders

As in the presented case, psychiatric abnormalities commonly exhibited by patients with LKS may lead to the suspicion of ASD [7, 8, 18, 20]. The timely conduction of a sleep EEG was essential for accurate diagnosis and early initiation of therapy. However, it should be emphasized that epilepsy frequently co‐occurs with ASD [21, 22], meaning that abnormal EEG findings do not rule out the presence of comorbid ASD.

6.3. Challenges in Language Evaluation for Non‐Native Speakers

Another challenge emerges in language testing for non‐native speakers. In the presented case, assessing the child's mother tongue was difficult due to the lack of availability and feasibility of standardized tests in the primary language in the clinical setting. A limitation of this case is the absence of standardized tests in the native language, which reduces the reliability of the language evaluation. Interestingly, the failure to acquire the new language after immigration was the leading reason for consultation. Especially in situations where diagnostic procedures are hindered by language barriers, the failure to learn a new language, alongside behavioral abnormalities and a typical EEG pattern of LKS, should be considered as a possible indication of language regression due to LKS.

6.4. Psychiatric Comorbidities and Management

The patient demonstrated social anxiety, stemming from the language deficit, which contributed to functional impairments. Therefore, treatment should not be exclusively limited to antiseizure measures, but should also encompass psychiatric support, CBT, and speech therapy.

6.5. Prognostic Factors

The prognosis in LKS is highly variable [16]. One study has shown that a longer duration of CSWS is linked to poor long‐term outcomes with persistent language impairment [17]. In our patient, the clinical response to treatment is a positive sign. However, the long untreated period with ongoing epileptic activity may have a negative impact. At present, a clear prognostic statement is not possible. Further research is needed to better define prognostic factors in LKS. The pathophysiology of the syndrome is still incompletely understood. It is possible that the prolonged exposure to electrical status epilepticus drives maladaptive plasticity during the critical period of language development [23]. This would explain the incomplete remission of the language deficits even after epileptic activity has ceased at the onset of puberty. Inflammatory processes triggered by the epileptic activity might further add to permanent deficits if not halted in time. Further clinical and experimental research is needed to clarify the pathophysiology of LKS. Although current findings are limited, they suggest that early diagnosis and treatment can significantly improve the long‐term prognosis for children with LKS and ameliorate the overall quality of life for the child and their family. This underscores the importance of interdisciplinary cooperation to promptly identify and address the condition.

Author Contributions

Dilara Tomal: conceptualization, data curation, investigation, writing – original draft, writing – review and editing. Sibylle Hodecker: conceptualization, data curation, investigation, writing – original draft, writing – review and editing. Konstantin Mechler: writing – review and editing. Sandra Gerstner: data curation, investigation. Steffen Syrbe: data curation, investigation, writing – review and editing. Alexander Haege: supervision, writing – review and editing.

Funding

The authors have nothing to report.

Consent

Written informed consent was obtained from the patient's parents and from the patient to publish this report in accordance with the journal's patient consent policy.

Conflicts of Interest

Alexander Haege and Konstantin Mechler received speaker fees from Shire/Takeda and Medice; these are unrelated to the current manuscript. Steffen Syrbe received speaker fees from JAZZ Pharma and UCB Pharma, not related to this publication.

Tomal D., Hodecker S., Mechler K., Gerstner S., Syrbe S., and Haege A., “Diagnostic Challenges and Consideration of Landau–Kleffner Syndrome as a Differential Diagnosis for Language Disorders: A Case Report,” Clinical Case Reports 13, no. 12 (2025): e71595, 10.1002/ccr3.71595.

Data Availability Statement

The data that support the findings of this study are derived from the patient's medical records and are not publicly available due to privacy and ethical restrictions, but may be available from the corresponding author upon reasonable request.