Abstracts

Rationale: Coffin Siris syndrome (CSS, MIM135900) is a rare multiple congenital anomaly syndrome caused by pathogenic variants in the BAF complex¹. Anomalies include intellectual disability and intracranial abnormalities such as corpus callosal dysgenesis², Dandy-Walker malformations³, neuronal heterotopias⁴, and simplified gyral patterns⁵. Up to 25-30% of patients with CSS develop epilepsy. This is the first comprehensive description of epilepsy, seizures types, treatment, and EEG findings in patients with CSS and utilizes the largest patient-driven registry of these patients.

Methods: The International CSS Patient Report Database was established in 2015 as a repository for clinical data on patients diagnosed with CSS. Information is entered by patient caregivers after self-referral or referral by medical providers. The database was queried for patients with seizures or epilepsy. Patient age, age at seizure onset, EEG abnormalities, brain imaging abnormalities, seizure therapy, and seizure types were analyzed. All enrollees have completed consents and surveys through the IRB approved protocol at Eastern Virginia Medical School (EVMS IRB 15-03-ex-0058).

Results: Twenty of 334 patients reported having seizures, EEG abnormalities, and/or epilepsy (Table 1). Eighteen patients (5.4%) reported seizures or epilepsy. One patient had only febrile seizures and three others described febrile seizures as well as epilepsy. Median age of seizure onset was 2.67 years (Interquartile range 3.33, SD 3.1). Six patients described focal seizures and one had generalized epilepsy, however an additional 4 patients reported “absence,” staring, or impaired awareness seizures without mention of onset type. Four patients (20%) were pharmacoresistant and one had received epilepsy surgery (VNS). Thirteen out of eighteen patients with seizures or epilepsy had an ARID1B variant (Table 2). One patient had a history of status epilepticus (CSSR3). Sixteen patients (4.8%) reported EEG abnormalities, the majority of which were described as focal or multifocal (87.5%). Two patients had an EEG consistent with Lennox-Gastaut syndrome.

Conclusions: Conclusion: The incidence of epilepsy in this self-report database was lower than in other case series but still significantly higher than the general population. When present, epilepsy tends to be easily controlled. EEGs typically note multifocal or focal abnormalities. This is the most comprehensive review of the characteristics of epilepsy in patients with CSS to date. It is limited by the self-report nature of the database.

Funding: Please list any funding that was received in support of this abstract.: none.