Landau–Kleffner Syndrome Can Herald the Diagnosis of GRIN2A Gene Mutation

TL;DR

This paper reports a case where Landau–Kleffner Syndrome led to the discovery of a GRIN2A gene mutation, linking language and seizure disorders to genetic causes.

Contribution

The paper highlights a rare case linking Landau–Kleffner Syndrome with a GRIN2A gene mutation, expanding understanding of its genetic basis.

Findings

A 5-year-old boy with aphasia and autistic-like behavior had a GRIN2A gene mutation identified.

Treatment with antiepileptic drugs improved speech and seizure control in the patient.

The case suggests Landau–Kleffner Syndrome may herald GRIN2A-related neurodevelopmental disorders.

Abstract

Landau–Kleffner syndrome is a rare age-related childhood epileptic syndrome of linguistic decline and neuropsychological abnormalities as main clinical symptoms. It is a functional language disorder of children, manifesting with auditory verbal agnosia and other predominantly linguistic deficits. Also, cognitive and neurophysiological–behavioural abnormalities might manifest. Clinical seizures have been reported in three-quarters of children. Recent advances in genomic studies have provided important insights into the understanding of neurodevelopmental disorders such as autistic spectrum disorder, intellectual disability, and epilepsy. N-methyl-D-aspartate receptors (NMDARs) are glutamate-gated channels that are essential for synaptic transmission and plasticity in the central nervous system. Impaired NMDAR signaling due to genetic mutation causes a constellation of neurodevelopmental disorders that manifest as intellectual disability, epilepsy, and schizophrenia. A mutation in the GRIN gene which encodes NMDAR subunits can disrupt NMDAR function. In this article, we describe a 5-year-old boy who presented with aphasia and autistic- like behavior; during evaluation, subtle myoclonic jerks were noticed. Electroencephalogram revealed a hypsarrhythmia-like pattern, and following treatment with antiepileptic medications, he showed remarkable improvement in speech with better seizure control. Comprehensive genomic testing identified a heterozygous pathogenic variant in the GRIN2A gene. It is fundamental to maintain an awareness of the possible etiology of different epilepsy syndromes. Further description of this condition is detailed in this article.