Exploring the clinical spectrum of CNTNAP2-related neurodevelopmental disorders: A case series and a literature appraisal

Giulia Barcia; Giovanna Scorrano; Marlène Rio; Cyril Gitiaux; Marie Hully; Karine Poirier; Claude Besmond; Arnold Munnich; Nathalie Boddaert; Nicole Chemaly; Rima Nabbout

doi:10.1016/j.ejmg.2024.104979

Exploring the clinical spectrum of CNTNAP2-related neurodevelopmental disorders: A case series and a literature appraisal

Eur J Med Genet. 2024 Oct 16:72:104979. doi: 10.1016/j.ejmg.2024.104979. Online ahead of print.

Authors

Affiliations

¹ Department of Genetics, Necker Enfants Malades University Hospital, AP-HP, Université Paris Cité, Paris, France. Electronic address: [email protected].
² Department of Pediatric Neurology, Reference Centre for Rare Epilepsies, Necker Enfants Malades University Hospital, AP-HP, Université Paris Cité, Paris, France.
³ Department of Genetics, Necker Enfants Malades University Hospital, AP-HP, Université Paris Cité, Paris, France.
⁴ Translational Genetics, National Institute of Health and Medical Research Mixed Unit of Research 1163, Imagine Institute, University of Paris, Paris, France.
⁵ Department of Pediatric Radiology, Necker Enfants Malades Hospital, AP-HP, Université Paris Cité, Paris, France.
⁶ Department of Pediatric Neurology, Reference Centre for Rare Epilepsies, Necker Enfants Malades University Hospital, AP-HP, Université Paris Cité, Paris, France; Imagine Institute, Laboratory of Translational Research for Neurological Disorders, INSERM UMR 1163, Paris, France.

PMID: 39423951
DOI: 10.1016/j.ejmg.2024.104979

Abstract

Biallelic pathogenic variants in CNTNAP2, a gene encoding the contactin-associated protein-like 2, have been reported in patients with various clinical presentations including intellectual disability (ID), autistic spectrum disorders (ASD), psychiatric disorders, and focal epilepsy rarely associated to focal cortical dysplasia. We report four children carrying novel biallelic CNTNAP2 pathogenic variants. They present global developmental delay, psychiatric disorders, and focal epilepsy. All patients displayed brain MRI abnormalities consistent with focal temporal dysplasia. One patient had a temporal resection before the availability of genetic testing. Focal cortical dysplasia represents a frequent finding related to focal refractory epilepsy in CNTNAP2 affected patients, and surgery seems to be ineffective in this setting. The genetic testing could therefore be impactful on treatment choices in refractory focal epilepsies.

Keywords: CNTNAP2; Focal cortical dysplasia; Genetic epilepsy; Germline mutations.

Publication types

Case Reports