Bilateral temporal lobe dysplasia and seizure onset associated with biallelic CNTNAP2 variants

Biallelic CNTNAP2 variants have been associated with Pitt-Hopkins-like syndrome. We describe six novel and one previously reported patients from six independent families and review the literature including 64 patients carrying biallelic CNTNAP2 variants. Initial reports highlighted intractable focal...

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Bibliographic Details
Published in:Epilepsia open 2024-02, Vol.9 (1), p.417-423
Main Authors: Panza, Norman, Bianchini, Claudia, Cetica, Valentina, Balestrini, Simona, Barba, Carmen, Ferrari, Anna Rita, Mei, Davide, Parmeggiani, Lucio, Parrini, Elena, Guerrini, Renzo
Format: Article
Language:English
Subjects:
Age
Child development
CNTNAP2
Convulsions & seizures
Epilepsy
focal cortical dysplasia
Genes
genetic epilepsy
Genotype & phenotype
Intellectual disabilities
Medical imaging
Neuroimaging
Patients
Short
Short s
temporal lobe epilepsy
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Summary:Biallelic CNTNAP2 variants have been associated with Pitt-Hopkins-like syndrome. We describe six novel and one previously reported patients from six independent families and review the literature including 64 patients carrying biallelic CNTNAP2 variants. Initial reports highlighted intractable focal seizures and the failure of epilepsy surgery in children, but subsequent reports did not expand on this aspect. In all our patients (n = 7), brain MRI showed bilateral temporal gray/white matter blurring with white matter high signal intensity, more obvious on the T2-FLAIR sequences, consistent with bilateral temporal lobe dysplasia. All patients had focal seizures with temporal lobe onset and semiology, which were recorded on EEG in five, showing bilateral independent temporal onset in four. Epilepsy was responsive to anti-seizure medications in two patients (2/7, 28.5%), and pharmaco-resistant in five (5/7, 71.5%). Splice-site variants identified in five patients (5/7, 71.5%) were the most common mutational finding. Our observation expands the phenotypic and genetic spectrum of biallelic CNTNAP2 alterations focusing on the neuroimaging features and provides evidence for an elective bilateral anatomoelectroclinical involvement of the temporal lobes in the associated epilepsy, with relevant implications on clinical management.
ISSN:2470-9239
2470-9239
DOI:10.1002/epi4.12843