Abstracts

Rationale:
This study aims to further expand the known epileptic phenotype of ARID1B mutation.

Methods: Case report.

Results:
A two month-old male presented with three episodes of perioral cyanosis and right eye deviation followed by apnea and bradycardia requiring tactile stimulation. The infant had a normal neurologic exam but was noted to have laryngomalacia with stridor at rest.  Continuous EEG was initiated and, after three days of normal monitoring, captured two seizures characterized by full body extensor stiffening followed by clinically significant apnea and bradycardia. Levetiracetam was initiated, but three days later an additional episode occurred which required cardiopulmonary resuscitation. The ictal EEG showed rhythmic theta and alpha activity in the right posterior quadrant, evolving to rhythmic spikes. Phenobarbital controlled the seizures. On genetic testing, the patient was found to have the ARID1B c.1160_1200del p.(A387Gfs*134) pathogenic variant.

Conclusions: ARID1B-related disorder, which includes over half the known cases of Coffin-Siris syndrome, presents along a spectrum with a phenotype including intellectual disability, hypertrichosis, laryngomalacia, cryptorchidism, and small or absent 5th distal phalanxes or nails. Seizures in case reports are predominantly focal-onset motor type presenting in toddler/childhood. Here, we describe an epileptic phenotype of focal-onset seizures at two months of age associated with life-threatening apnea and bradycardia, occurring in clusters three days apart, with a normal interictal EEG. Furthermore, there was a lack of response to levetiracetam, and seizure control was ultimately achieved with phenobarbital monotherapy. This expanded characterization better informs management, including need for subspecialty (cardiology, pulmonology) involvement, as well as antiseizure medication choice and prognostic considerations.

Funding: None