The case report published in Epilepsy & Behavior Reports (2025) describes a unique clinical presentation of ARID1B-related Coffin-Siris syndrome (CSS) involving medically refractory epilepsy.
Abstract Summary
The article documents a pediatric patient with CSS who developed severe, drug-resistant epilepsy. Imaging revealed specific brain malformations (pachygyria and polymicrogyria) in the right frontal lobe. Following a surgical disconnection of the epileptogenic zone, the patient achieved complete seizure freedom and showed significant improvements in speech and motor skills. This case is significant because it expands the known symptoms of CSS and highlights the effectiveness of surgical intervention in certain genetic epilepsies.
Key Findings
1. Rare Clinical Presentation
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Atypical Epilepsy: While CSS is often associated with mild epilepsy that responds well to medication, this patient suffered from Developmental and Epileptic Encephalopathy (DEE). Her condition was “medically refractory,” meaning multiple anti-seizure medications failed to control it.
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Structural Abnormalities: MRI and PET scans identified focal pachygyria (broad, thick gyri) and polymicrogyria (excessive small folds) in the right frontal lobe. This specific neuropathological combination had not been previously described in CSS literature.
2. Genetic Discovery
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The patient had a specific mutation in the ARID1B gene (a frameshift variant: p.Gly434Alafs12*). ARID1B is a critical component of the BAF complex, which regulates gene expression.
3. Surgical Success
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Procedure: A customized surgical disconnection of the affected right frontal sub-lobe was performed using 3D cerebral modeling for guidance.
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Outcome: At the 18-month follow-up, the patient was seizure-free (Engel Class IA).
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Developmental Gains: Beyond seizure control, the patient regained lost developmental milestones, showing improvements in her ability to speak and her physical strength.
4. Histopathology
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Analysis of the removed brain tissue confirmed Focal Cortical Dysplasia (FCD) Type IIa. This finding suggests that the genetic mutation likely caused localized brain malformations that served as the “trigger” for the seizures.
Conclusion & Recommendations
The authors conclude that:
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Genetic Testing is Crucial: Early genetic testing is essential for children with developmental and epileptic encephalopathy.
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Surgery is a Viable Option: Even in genetic syndromes, if a localized structural abnormality is found, surgery should be considered early to prevent further developmental regression and improve the quality of life.