The identification of the IRF2BPL c.2152del variant marks a significant milestone in understanding the genetic landscape of NEDAMSS. This rare neurodevelopmental disorder involves regression, abnormal movements, loss of speech, and seizures. Recently, clinical researchers detailed a male child presenting with a de novo frameshift mutation. This specific case confirms a severe phenotypic pattern involving drug-resistant epilepsy and profound developmental impairment. Notably, clinicians are increasingly utilizing exome sequencing (ES) to pinpoint these variants in neonatal cases.

Clinical Presentation of the IRF2BPL c.2152del Variant

Neonatal axial hypotonia often serves as an initial clinical indicator of this condition. In this patient, the epilepsy rapidly evolved into West Syndrome, a severe form of infantile spasms. Furthermore, brain MRI findings provided high diagnostic specificity. Imaging revealed corpus callosum thinning and hippocampal malrotation. In addition, EEG patterns progressed from burst-attenuation to hypsarrhythmia. Consequently, these findings highlight the aggressive nature of the disorder when this specific frameshift mutation is present.

Comparative Phenotypic Analysis of NEDAMSS

A comparative study of three patients carrying the IRF2BPL c.2152del variant revealed striking similarities. All individuals exhibited profound hypotonia and severe neurodevelopmental impairment from a very early age. However, the severity of drug-resistant epilepsy remains the most challenging aspect for clinicians to manage. In summary, these findings strongly suggest that this variant is associated with one of the most severe forms of NEDAMSS reported to date. Therefore, early genetic recognition remains vital for pediatric neurologists to provide accurate family counseling and personalized care.

FAQs

What is the IRF2BPL c.2152del variant?

It is a de novo frameshift mutation in the IRF2BPL gene. It typically results in a severe form of NEDAMSS characterized by early-onset epilepsy and developmental regression.

How is this variant diagnosed in clinical practice?

Clinicians identify the variant through exome sequencing (ES). Common findings include axial hypotonia in neonates and specific brain MRI anomalies like corpus callosum thinning.

What is the prognosis for children with this mutation?

The phenotype is generally severe. Most patients experience drug-resistant seizures, West Syndrome, and significant loss of motor and speech skills during infancy.

Disclaimer: This content is for informational and educational purposes only. It does not constitute professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Refer to the latest local and national guidelines for clinical practice.

References

von Quednow E et al. Recurrent IRF2BPL c.2152del Variant in NEDAMSS: A Case Report and Comparative Analysis. Am J Med Genet A. 2026 Mar 11. doi: 10.1002/ajmg.a.70113. PMID: 41813602.

Marcogliese PC, et al. IRF2BPL Is Required for Neuronal Maintenance and its Loss Causes Progressive Neurodegeneration. Am J Hum Genet. 2018;103(2):174-189.

Vanagunas T, Seiwert EU, Larsh TR, et al. IRF2BPL-Related Disorder. 2024 Nov 21. In: Adam MP, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2024.